Assessing drug uptake and response differences in 2D and 3D cellular environments using stimulated Raman scattering microscopy.

The architecture of cell culture-two-dimensional (2D) versus three-dimensional (3D)-significantly impacts various cellular factors, including cell-cell interactions, nutrient and oxygen gradients, metabolic activity, and gene expression profiles. This can result in different cellular responses during cancer drug treatment, with 3D-cultured cells often exhibiting higher resistance to chemotherapeutic drugs. While various genetic and proteomic analyses have been employed to investigate the underlying mechanisms of this increased resistance, complementary techniques that provide experimental evidence of spatial molecular profiling data are limited. Stimulated Raman scattering (SRS) microscopy has demonstrated its capability to measure both intracellular drug uptake and growth inhibition. In this work, we applied three-band SRS imaging to 2D and 3D cell cultures and provided a comparative analysis of drug uptake and response with the goal of understanding whether the difference in drug uptake explains the drug resistance in 3D culture compared to 2D. Our investigations revealed that despite similar intracellular drug levels in 2D and 3D A549 cells during lapatinib treatment, the growth of 3D spheroids is less impacted, supporting an enhanced drug tolerance in the 3D microenvironment. We further elucidated drug penetration patterns and the resulting heterogeneous cellular responses across different spheroid layers. Additionally, we investigated the role of the extracellular matrix in modulating drug delivery and cell response, and we discovered that limited drug penetration in 3D could also contribute to lower drug response. Our study provides valuable insights into the intricate mechanisms of increased drug resistance in 3D tumor models during cancer drug treatments.

Mentorship Landscape and Common Practices in an Academic Pharmacy Association.

OBJECTIVES: To explore the landscape of mentorship within professional associations in pharmacy academia, including reviewing available literature and describing currently available programs within the American Association of Colleges of Pharmacy, and recommend key considerations for the development of mentorship programs within professional associations. FINDINGS: A literature review of mentorship programs within professional associations for pharmacy academics was conducted, with a total of 5 articles identified and summarized. Additionally, a survey was conducted to determine the landscape of available mentorship programs within American Association of Colleges of Pharmacy affinity groups to capture unpublished experiences. Information regarding common characteristics and assessment methods was collected for groups that have mentorship programs, while needs and barriers were collected for those who did not. SUMMARY: Literature, while limited, supports positive perceptions of mentorship programs within professional associations. Based on the responses and working group experience, several recommendations are proposed for mentorship program development, including the need for clearly defined goals, relevant program outcomes, association support to reduce redundancies and promote participation, and, in some cases, implementation of an association-wide program to ensure access to mentorship.

Incorporation of yoga in pharmacy education.

BACKGROUND: The well-being of pharmacists is critical to support personal and professional health. Identifying and integrating a variety of practices that promote wellness is prudent for schools/colleges of pharmacy so students may form habits before entering the profession as practitioners. Yoga, a practice that combines muscular activity with mindfulness, can be incorporated with minimal resources via numerous mechanisms within and outside of the curriculum. METHODS: The objective was to provide a summary of various strategies incorporating yoga in pharmacy professional curricula as well as detail various approaches to integrating yoga into pharmacy curricula. Literature was evaluated across professional pharmacy programs pertaining to yoga knowledge, beliefs, approaches, and benefits. RESULTS: Ten articles about yoga awareness, knowledge, beliefs, and benefits in professional pharmacy curricula were identified. Improvement in mental health and decreased stress were recognized as benefits. Within schools/colleges of pharmacy, yoga programming has been included in required as well as elective courses, co-curriculum programming, extracurricular activities, and post-graduate training. IMPLICATIONS: Schools of pharmacy can consider incorporation of yoga practice into curricula as a tool to promote well-being and resiliency.

Coping, resilience, and emotional well-being in pharmacy students during the COVID-19 pandemic.

INTRODUCTION: The purpose of this study was to investigate the significant contributions of coping, resilience, personal characteristics, and health behaviors on the emotional well-being of pharmacy students during the COVID-19 pandemic. COVID-19 was identified in December 2019 and declared a pandemic by the World Health Organization in March 2020. Pharmacy students may experience greater stress during this outbreak because of interruptions in classes or rotations, concerns regarding personal or family health, and social isolation from peers. These changes may result in behavior shifts, difficulty concentrating, and increased use of negative coping strategies. The extent to which these factors affect overall student well-being during a pandemic is largely unknown. METHODS: A cross-sectional study of 3 colleges of pharmacy was completed during May to July 2020 via an online, anonymous 64-item questionnaire using REDCap software. Linear regression and descriptive statistical analyses were conducted using SPSS version 26. RESULTS: Using the enter method, levels of coping strategies, personal resilience, and Hispanic ethnic identity explain 29% of the variance in emotional well-being scores in pharmacy students during the first months of the COVID-19 pandemic (F (2,76) = 11.785, P < .000, R2 = 0.317, R2 adjusted = 0.291). For this sample (N = 104), higher levels of resilience, greater use of coping strategies, and identifying as Hispanic were significant predictors of emotional well-being. DISCUSSION: Student mental health continues to be important, especially during crises and pandemics. Therefore, pharmacy programs should cultivate an environment that supports the emotional well-being of their students. Campus-based initiatives may be needed to encourage healthy coping behaviors and bolster students' personal resilience to better prepare them for providing front-line patient care in the future.

Practical points for applying herpes zoster vaccine recommendations.

The recombinant zoster vaccine (Shingrix) was approved to help combat the incidence of shingles in patients age 50 years and older and the CDC now recommends it over the zoster vaccine live (Zostavax). This article highlights practical considerations to help clinicians appropriately apply the most recent vaccine recommendations to their patients.

Daptomycin dosing in obese patients: analysis of the use of adjusted body weight versus actual body weight.

BACKGROUND: Food and Drug Administration-approved daptomycin dosing uses actual body weight, despite limited dosing information for obese patients. Studies report alterations in daptomycin pharmacokinetics and creatine phosphokinase elevations associated with higher weight-based doses required for obese patients. Limited information regarding clinical outcomes with alternative daptomycin dosing strategies in obesity exists. OBJECTIVE: This study evaluates equivalency of clinical and safety outcomes in obese patients with daptomycin dosed on adjusted body weight versus a historical cohort using actual body weight. METHODS: This retrospective, single center study compared equivalency of outcomes with two one-sided tests in patients with body mass index ⩾30 kg/m2 who received daptomycin dosed on actual body weight versus adjusted body weight. The primary outcome was clinical failure. Secondary outcomes included 90-day readmission and 90-day mortality. A combined safety endpoint included creatine phosphokinase elevation, patient-reported myopathy, and rhabdomyolysis. RESULTS: A total of 667 patients were screened for inclusion; 101 patients were analyzed with 50 in the actual body weight cohort and 51 in the adjusted body weight cohort. The two regimens were statistically equivalent for clinical failure (2% actual body weight versus 4% adjusted body weight; p < 0.001 for equivalency). The two regimens were also statistically equivalent for 90-day mortality (6% actual body weight versus 4% adjusted body weight; p = 0.0014 for equivalency). Limitations include single center, retrospective design, and sample size. Daptomycin dosing intensified throughout the study period. CONCLUSION: The two daptomycin dosing cohorts were statistically equivalent for both clinical failure and 90-day mortality. More data are needed to assess outcomes with higher (⩾8 mg/kg/day) daptomycin doses in this patient population.

Pembrolizumab-induced myasthenia gravis: A fatal case report.

Purpose Pembrolizumab, a monoclonal antibody which inhibits the programmed cell death 1 receptor, has been shown to efficaciously enhance pre-existing immune responses to malignancies. However, safety concerns must also be considered as pembrolizumab use has been associated with several life-threatening immune-related adverse events (irAEs). We report a fatal case of pembrolizumab-induced myasthenia gravis in a patient with no prior myasthenia gravis history. Case report A 63-year-old male presented with right eyelid drooping, puffiness, blurred vision, and shortness of breath two weeks after an initial infusion of pembrolizumab. He was subsequently diagnosed with new onset acetylcholine-receptor positive myasthenia gravis. Despite aggressive treatment with corticosteroids, pyridostigmine, intravenous immunoglobulin, and plasmapheresis, the patient clinically deteriorated and ultimately expired from acute respiratory failure after a 12-day hospitalization. Discussion Current package labeling for pembrolizumab warns against various irAEs associated with its use including pneumonitis, colitis, and endocrinopathies. To date, only one case of new onset myasthenia gravis and two case reports of myasthenia gravis exacerbation have been identified. This case further highlights the mortality risk associated with development of irAEs. Conclusion While rare, evidence for the development of MG associated with pembrolizumab is growing. Prompt recognition of symptoms and discontinuation of pembrolizumab is necessary to help improve prognosis.

ß-Blockade in Heart Failure With Reduced Ejection Fraction: Does Heart Rate Control Influence Readmissions?

BACKGROUND: Raised resting heart rate (HR), >70 beats per minute (bpm), has been shown to be a risk factor for adverse cardiovascular outcomes and hospital readmissions, specifically in patients with heart failure with reduced ejection fraction (HF rEF). Given their mortality benefit, ß-blockers are recommended in HF rEF, with a goal to titrate to a maximum tolerated dose rather than a specific HR target. OBJECTIVE: To determine the impact of optimal HR control achievement prior to hospital discharge on hospital readmissions in patients with HF rEF receiving ß-blockade. METHODS: A retrospective study of patients admitted to 5 adult hospitals within a large urban health-care system, between 2013 and 2015, was conducted. Patients were identified via International Classification of Diseases, Ninth Revision ( ICD-9) coding for acute on chronic HF rEF. RESULTS: Of the 225 patients included, 20% achieved optimal HR control (n = 46, HR <70 bpm; n = 179, HR ≥70 bpm) and only 15% received ß-blocker titration during hospital admission. Of note, 25% of patients receiving ≥50% target dose (n = 79) and 28% receiving 100% target dose (n = 39) achieved optimal HR control. At 30 days, patients with an HR <70 bpm versus HR ≥70 bpm exhibited similar readmission rates (9% vs 11%, respectively; P > .99) and ED visits (11% vs 8%, respectively; P = .57). CONCLUSIONS: Readmission rates were similar among patients with HF rEF despite the majority failing to achieve optimal HR control from ß-blockade. However, ß-blocker dosing remains suboptimal relative to guideline-recommended target doses. Opportunities exist for inpatient clinicians to optimize ß-blockade in an attempt to achieve HR control.

Transgender students in pharmacy school, part 1: What academic administrators need to know.

While gender transition is a very exciting time for most students embarking upon this personal journey, it is not without its stressors as well. For students choosing to further their education and become pharmacists, the complexity and demands of pharmacy education during the transition period can be one such additive stressor. As pharmacy educators and administrators, we have the ability to help shape this professional journey and alleviate stress by maintaining our obligation to provide a safe and non-discriminatory learning environment for all students. Therefore, this two-part commentary will serve as a means to provide information and insights to administrators and faculty advisors in order to ensure transgender students, including those actively undergoing gender transition, achieve both a successful transition and pharmacy school career.

Transgender students in pharmacy school part 2: How faculty advisors can support their advisees.

Faculty advisors serve a critical role in the success of pharmacy students during their academic careers, frequently serving as a problem-solver or sounding board during times of both triumph and struggle. Additionally, faculty advisors help students overcome barriers along their journey to ensure a successful progression through pharmacy school. This role is particularly important to transgender students, given the additional barriers they may face, which were highlighted in Part One of the commentary on transgender students in pharmacy school. To help faculty serve as a successful mentor to transgender advisees, Part Two of the commentary provides resources and insights into advising transgender students, including those actively undergoing gender transition.

Angioedema Spotlight: A Closer Examination of Sacubitril/Valsartan Safety Results.

Incorporation of neprilysin inhibition into heart failure pharmacotherapy regimens has recently been recommended by U.S. guidelines, based on results from the PARADIGM-HF trial comparing sacubitril/valsartan to enalapril. While most of the discussion has focused on efficacy, a closer examination of the safety results, particularly the incidence of angioedema during the run-in and double-blind periods, is also warranted. Although no major safety concerns were identified, an angioedema risk comparable to enalapril was found, primarily in the black population. Therefore, despite combination with an angiotensin receptor blocker, which historically has a lower incidence of angioedema, the addition of neprilysin inhibition yields an angioedema risk profile comparable to angiotensin converting enzyme (ACE) inhibitors. Clinicians should recognize this safety risk when prescribing sacubitril/valsartan and remain vigilant in counseling patients regarding the signs and symptoms of angioedema. As recommended by the guidelines, avoiding sacubitril/valsartan use concurrently or within 36 hours of the last dose of an ACE inhibitor or in patients with a history of angioedema is also crucial to minimize angioedema risk and prevent patient harm.

Direct oral anticoagulant use in nonvalvular atrial fibrillation with valvular heart disease: a systematic review.

Direct oral anticoagulants (DOACs) are indicated for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF), which, according to the American College of Cardiology/American Heart Association/Heart Rhythm Society atrial fibrillation (AF) guidelines, excludes patients with rheumatic mitral stenosis, a mechanical or bioprosthetic heart valve, or mitral valve repair. However, the data regarding use of DOACs in AF patients with other types of valvular heart disease (VHD) are unclear. We aimed to summarize and evaluate the literature regarding the safety and efficacy of DOAC use in NVAF patients with other types of VHD. After an extensive literature search, a total of 1 prospective controlled trial, 4 subanalyses, and 1 abstract were identified. Efficacy of the DOAC agents in NVAF patients with VHD mirrored the overall trial results. Bleeding risk was significantly increased in VHD patients treated with rivaroxaban, but not for dabigatran or apixaban. Of the bioprosthetic valve patients enrolled in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, no safety or efficacy concerns were identified. In conclusion, subanalyses of DOAC landmark AF trials revealed that dabigatran, rivaroxaban, and apixaban may be safely used in AF patients with certain types of VHD: aortic stenosis, aortic regurgitation, and mitral regurgitation. More evidence is needed before routinely recommending these agents for patients with bioprosthetic valves or mild mitral stenosis. Patients with moderate to severe mitral stenosis or mechanical valves should continue to receive warfarin, as these patients were excluded from all landmark AF trials.

Pharmacologic Treatment of Alcoholic Hepatitis: Examining Outcomes Based on Disease Severity Stratification.

OBJECTIVES: Maddrey discriminant function (MDF) score is a measure of disease prognosis in alcoholic hepatitis (AH) used to identify patients at highest risk of mortality and determine the need for initiation of pharmacologic treatment. The purpose of this study was to evaluate the effects of pharmacologic therapy for hospitalized AH patients as stratified by MDF score. METHODS: A retrospective review of patients with an AH diagnosis admitted to a Methodist LeBonheur Healthcare adult hospital between 06/2009 and 06/2014 was conducted. Patients ≥18 years of age with an ICD-9 code for AH were evaluated. RESULTS: Of the 493 patients screened, 234 met the inclusion criteria, comprised of 62 patients with an MDF ≥ 32 (treatment, n = 42 vs. no treatment, n = 20) and 172 patients with an MDF < 32 (treatment, n = 15 vs. no treatment, n = 157). For the patients with an MDF ≥ 32, there was no statistically significant difference between the treatment group vs. non-treatment group regarding 28-day mortality (31% vs. 11%, respectively; P = 0.18) and 6-month mortality (45% treatment vs. 38% non-treatment; P = 0.75). For the patients with an MDF <32, there was no statistically significant difference between the treatment group vs. non-treatment group regarding 28-day mortality (0% vs. 7%, respectively; P > 0.99) and 6-month mortality (11% treatment vs. 13% non-treatment; P > 0.99). There was no difference in incidence of acute kidney injury, hepatorenal syndrome, development of infection or hepatic encephalopathy between the treatment vs. non-treatment groups. CONCLUSIONS: Pharmacologic treatment showed no survival benefit, regardless of disease severity. Given the mortality risk seen in mild-moderate AH patients not receiving treatment and concern for a possible treatment ceiling effect in severe AH patients, more data are needed to adequately assess the utility of MDF in selecting appropriate candidates for AH treatment.

Ivabradine: A Review of Labeled and Off-Label Uses.

Ivabradine is a unique medication recently approved in the USA for the treatment of select heart failure patients. It was first approved for use in several countries around the world over a decade ago as an anti-anginal agent, with subsequent approval for use in heart failure patients. Since ivabradine has selective activity blocking the I f currents in the sinus node, it can reduce heart rate without appreciable effects on blood pressure. Given this heart-rate-specific effect, it has been investigated in many off-label indications as an alternative to traditional heart-rate-reducing medications such as beta blockers and calcium channel blockers. We conducted searches of PubMed and Google Scholar for ivabradine, heart failure, HFrEF, HFpEF, angina, coronary artery disease, inappropriate sinus tachycardia, postural orthostatic hypotension, coronary computed tomography angiography and atrial fibrillation. We reviewed and included studies, case reports, and case series published between 1980 and June 2016 if they provided information relevant to the practicing clinician. In many cases, larger clinical trials are needed to solidify the benefit of ivabradine, although studies indicate benefit in most therapeutic areas explored to date. The purpose of this paper is to review the current labeled and off-label uses of ivabradine, with a focus on clinical trial data.

Asthma as a Comorbidity in Hospitalized Patients: A Potential Missed Opportunity to Intervene.

Asthma is a frequent comorbidity in hospitalized children and adults. Patients with a history of asthma may have no breathing complaints or abnormal chest exam findings to trigger care for this comorbidity during hospitalization. Consequently, this may lead to a potential missed opportunity to discuss asthma as a comorbidity and ongoing issue to ensure its optimal management at home. Our goal is to raise awareness that such patient encounters may represent opportunities for health care professionals to optimize asthma management. Despite focusing on the present illness and limited time availability, asthma care may be improved in a time-efficient manner in these patients.