Warfarin Monitoring in Safety-Net Health Systems: Analysis by Race/Ethnicity and Language Preference.

BACKGROUND: Racial/ethnic disparities in anticoagulation management are well established. Differences in warfarin monitoring can contribute to these disparities and should be measured. OBJECTIVE: We assessed for differences in international normalized ratio (INR) monitoring by race/ethnicity and language preference across safety-net care systems serving predominantly low-income, ethnically diverse populations. DESIGN: Cross-sectional analysis of process and safety data shared from the Safety Promotion Action Research and Knowledge Network (SPARK-Net) initiative, a consortium of five California safety-net hospital systems. PARTICIPANTS: Eligible patients were at least 18 years old, received warfarin for at least 56 days during the measurement period from July 2015 to June 2017, and had INR testing in an ambulatory care setting at a participating healthcare system. MAIN MEASURES: We conducted a scaled Poisson regression for adjusted rate ratio of having at least one INR checked per 56-day time period for which a patient had a warfarin prescription. Adjusting for age, sex, healthcare system, and insurance status/type, we assessed for racial/ethnic and language disparities in INR monitoring. KEY RESULTS: Of 8129 patients, 3615 (44%) were female; 1470 (18%), Black/African American; 3354 (41%), Hispanic/Latinx; 1210 (15%), Asian; 1643 (20%), White; and 452 (6%), other. Three thousand five hundred forty-nine (45%) were non-English preferring. We did not observe statistically significant disparities in the rate of appropriate INR monitoring by race/ethnicity or language; the primary source of variation was by healthcare network. Older age, female gender, and uninsured patients had a slightly higher rate of appropriate INR monitoring, but differences were not clinically significant. CONCLUSIONS: We did not find a race/ethnicity nor language disparity in INR monitoring; safety-net site was the main source of variation.

Designing and Implementing an Electronic Patient Registry to Improve Warfarin Monitoring in the Ambulatory Setting.

BACKGROUND: Warfarin requires individualized dosing and monitoring in the ambulatory setting for protection against thromboembolic disease. Yet in multiple settings, patients spend upwards of 30% of time outside the therapeutic range, subjecting them to an increased risk of adverse events. At an urban, publicly funded clinic, the electronic health record (EHR) would not support integration with extant warfarin management software, which led to the creation and implementation of an electronic patient registry and a complementary team-based work flow to provide real-time health-system-level data for warfarin patients. METHODS: Creation of the registry, which began in August 2014, entailed use of an existing platform, which could interface with the outpatient EHR. The registry was designed to help ensure regular testing and monitoring of patients while enabling identification of patients and subpopulations with suboptimal management. The work flow used for the clinic's warfarin patients was also redesigned. An assessment indicated that the registry identified 341 (96%) of 357 patients actively seen in the clinic. RESULTS: For the cohort of the 357 patients in the registry, the no-show rate decreased from 31% (preimplementation, August 2014-December 2014) to 21% (postimplementation, January 2015-November 2015). The ratio of visits to no-shows increased from 2.3 to 4.0 visits. CONCLUSION: Design and implementation of an electronic registry in conjunction with a complementary work flow established an active tracking system that improved treatment monitoring for patients on anticoagulation therapy. Registry creation also facilitated assessment of the quality of care and laid the groundwork for ongoing evaluation and quality improvement efforts.

The emerging role of tiotropium for patients with asthma.

OBJECTIVE: To review clinical data on the use of the long-acting anticholinergic agent tiotropium in patients with asthma. DATA SOURCES: A literature search was performed via EMBASE and MEDLINE (1966-November 2012). The search was limited to human data published in the English language. Search terms included asthma, tiotropium, and long-acting anticholinergics. STUDY SELECTION AND DATA EXTRACTION: Relevant information related to the use of tiotropium in patients with asthma was reviewed. Randomized controlled trials and open-label trials were included. The references of published articles identified in the search were also examined for additional studies appropriate to include in the review. Data were prioritized if they originated from human studies, especially if derived from randomized, placebo-controlled trials. Trials and case reports involving the use of long-acting anticholinergic tiotropium in asthma patients were included; conversely, trials involving ipratropium were not. DATA SYNTHESIS: Two large randomized controlled trials support the safety and efficacy of adding tiotropium to the treatment regimen of select patients with poorly controlled asthma already receiving combination high-dose glucocorticosteroid/long-acting ß-agonist (LABA) therapy. Pharmacogenomic studies have shown that patients with polymorphisms of the ß2-adrenoreceptor (ADRB2; 16 Arg/Arg and 16 Arg/Gly) are particularly responsive to treatment with tiotropium. Smaller studies indicate that the advantages may be most pronounced in patients with a predominance of sputum neutrophils and that tiotropium can assist with decreasing the inhaled corticosteroid (ICS) dose. An increased risk of cardiovascular events was not identified. CONCLUSIONS: Tiotropium should be considered in patients with asthma who remain symptomatic while receiving high-dose ICS and LABA therapy. Specifically, patients with high sputum neutrophil levels or with 16 Arg/Arg or 16 Arg/Gly polymorphism of the ADRB2 gene appear to respond best.

Medication adverse events in the ambulatory setting: A mixed-methods analysis.

PURPOSE: To characterize ambulatory care adverse drug events reported to the Collaborative Healthcare Patient Safety Organization (CHPSO), a network of 400 hospitals across the United States, and identify addressable contributing factors. METHODS: We abstracted deidentified ambulatory care CHPSO reports compiled from May 2012 to October 2018 that included medication-related adverse events to identify implicated medications and contributing factors. We dual-coded 20% of the sample. We quantitatively calculated co-occurring frequent item sets of contributing factors and then applied a qualitative thematic analysis of co-occurring sets of contributing factors for each drug class using an inductive analytic approach to develop formal themes. RESULTS: Of 1,244 events in the sample, 208 were medication related. The most commonly implicated medication classes were anticoagulants (n = 97, or 46% of events), antibiotics (n = 24, 11%), hypoglycemics (n = 19, 9%), and opioids (n = 17, 8%). For anticoagulants, timely follow-up on supratherapeutic international normalized ratio (INR) values occurred before the development of symptoms. Incident reports citing antibiotics often described prescribing errors and failure to review clinical contraindications. Reports citing hypoglycemic drugs described low blood sugar events due to a lack of patient education or communication. Reports citing opioids described drug-drug interactions, commonly involving benzodiazepines. CONCLUSION: Ambulatory care prescribing clinicians and community pharmacists have the potential to mitigate harm related to anticoagulants, antibiotics, hypoglycemics, and opioids. Recommendations include increased follow-up for subtherapeutic INRs, improved medical record integration and chart review for antibiotic prescriptions, enhanced patient education regarding hypoglycemics, and alerts to dissuade coprescription of opioids and benzodiazepines.

Evaluating the primary care clinical pharmacist visit transition to telehealth during the COVID-19 pandemic by comparing medication related problems from telehealth visits and in-person visits.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic forced healthcare systems to rethink healthcare delivery, and forced primary care pharmacists in our healthcare system to switch all visits that were previously face to face (FTF) to telehealth. METHODS: We conducted a retrospective observational cohort study to examine the association between medication related problems (MRPs) resolved in telehealth vs FTF primary care clinical pharmacist visits. The telehealth visits took place in the context of the COVID-19 pandemic, which forced health care systems to rethink care delivery. Data was collected for patient visits for 2 weeks in January before the pandemic and 2 weeks in June during the pandemic. RESULTS: There was significantly more average MRPs resolved per patient encounter in FTF visits compared with telehealth visits, particularly in patient encounters that were previously seen by the pharmacist, who were under 65 years old, identified as Black/African American, had chronic kidney disease but not on dialysis, diabetes with end organ damage, and had uncontrolled blood pressure and uncontrolled A1c. CONCLUSION: These results provide a start to establish criteria for which patients should be seen by a clinical pharmacist in person vs over the phone.

A Qualitative Analysis of Outpatient Medication Use in Community Settings: Observed Safety Vulnerabilities and Recommendations for Improved Patient Safety.

OBJECTIVE: The aim of the study was to analyze diverse patients' experiences throughout the medication use process to inform the development of overarching interventions that support safe medication use in community settings. METHODS: Using a qualitative observational approach, we conducted approximately 18 hours of direct observation of the medication use process across multiple settings for a sample of vulnerable, high-risk patients. Observers recorded detailed field notes during the observations. To enrich the observational findings, we also conducted six semistructured interviews with medication safety experts representing a diversity of perspectives. Barriers and facilitators to safe medication use were identified based on inductive coding of the data. RESULTS: A variety of safety vulnerabilities plague all stages of the medication use process and many of the well-established evidence-based interventions aimed at improving the safety of medication use at key stages of the process have not been widely implemented in community settings observed in this study. Key safety vulnerabilities identified include: limited English proficiency, low health literacy, lack of clinician continuity, incomplete medication reconciliation and counseling, unsafe medication storage and disposal habits, and conflicting healthcare agendas with caregivers. CONCLUSIONS: Our findings underscore a need for overarching, comprehensive interventions that span the entire process of medication use, including integrated communication systems between clinicians, pharmacies, and patients, and a "patient navigator" program that assists patients in navigating the entire medication-taking process. Collective ownership of the medication management system and mutual motivation for devising collaborative solutions is needed among key sectors.

Platinum(II) Drug-Loaded Gold Nanoshells for Chemo-Photothermal Therapy in Colorectal Cancer.

In the present study, we utilize a poly[2-(N,N-dimethylamino)ethyl methacrylate]-poly(ε-caprolactone) (PDMA-PCL) micellar template-based gold nanoshell as a nanocarrier of a platinum-based chemotherapeutic drug, dichloro(1,2-diaminocyclohexane)platinum(II) (DACHPt). The gold nanoshells not only function as a drug delivery platform but also provide a remarkable photothermal effect, resulting in synergistically combined chemo-photothermal therapy. With the positively charged outstretched hydrophilic PDMA segments, chloroauric anions are attracted to the PDMA-PCL micellar surface and reduced to gold atoms in situ, forming small seeds that nucleate the subsequent growth of gold nanoshells. The DACHPt-loaded gold nanoshells possess strong absorption in the near-infrared (NIR) region and outstanding photothermal conversion effect; thus, they can promote a temperature increase that is sufficient to ablate tumor cells under NIR laser irradiation at a moderate power density (1 W/cm2). Furthermore, by exploiting the synergistic effects of platinum-based chemotherapy and photothermal therapy, the DACHPt-loaded gold nanoshells exhibited a profound inhibition of tumor growth compared to chemotherapy or photothermal therapy alone. Therefore, the platinum(II)-loaded gold nanoshells that we proposed herein may be a potential alternative for efficient curative therapy for colorectal cancer.

Evaluation of a Health Information Technology-Enabled Panel Management Platform to Improve Anticoagulation Control in a Low-Income Patient Population: Protocol for a Quasi-Experimental Design.

BACKGROUND: Warfarin is one of the most commonly prescribed medications in the United States, and it causes a significant proportion of adverse drug events. Patients taking warfarin fall outside of the recommended therapeutic range 30% of the time, largely because of inadequate laboratory monitoring and dose adjustment. This leads to an increased risk of blood clots or bleeding events. We propose a comparative effectiveness study to examine whether a technology-enabled anticoagulation management program can improve long-term clinical outcomes compared with usual care. OBJECTIVE: Our proposed intervention is the implementation of an electronic dashboard (integrated into a preexisting electronic health record) and standardized workflow to track patients' laboratory results, identify patients requiring follow-up, and facilitate the use of a validated nomogram for dose adjustment. The primary outcome of this study is the time in therapeutic range (TTR) at 6 months post intervention (a validated metric of anticoagulation quality among patients receiving warfarin). METHODS: We will employ a pre-post quasi-experimental design with a nonequivalent usual-care comparison site and a difference-in-differences approach to compare the effectiveness of a technology-enabled anticoagulation management program compared with usual care at a large university-affiliated safety-net clinic. RESULTS: We used a commercially available health information technology (HIT) platform to host a registry of patients on warfarin therapy and create the electronic dashboard for panel management. We developed the intervention with, and for, frontline clinician users, using principles of human-centered design. This study is funded until September 2020 and is approved by the University of California, San Francisco Institutional Review Board until June 22, 2020. We completed data collection in September 2019 and expect to complete our proposed analyses by February 2020. CONCLUSIONS: We anticipate that the intervention will increase TTR among patients taking warfarin and that the use of this HIT platform will facilitate tracking and monitoring of patients on warfarin, which could enable outreach to those overdue for visits or laboratory monitoring. We will use these findings to iteratively improve the platform in preparation for a larger, multiple-site, pragmatic clinical trial. If successful, our study will demonstrate the integration of HIT platforms into existing electronic health records to improve patient care in real-world clinical settings. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/13835.

Dual-triggered drug-release vehicles for synergistic cancer therapy.

Cancer is a complex and tenacious disease. Drug-delivery systems in combination with multimodal therapy strategies are very promising candidates for cancer theranostic applications. In this study, a new drug-delivery vehicle that combine human serum albumin (HSA)- and poly(sodium 4-styrenesulfonate) (PSS)-coated gold nanorod nanoparticles(GNR/PSS/HSA NPs) was developed for synergistic cancer therapy. Doxorubicin (DOX) was loaded onto GNR/PSS/HSA NPs, by electrostatic and hydrophobic forces, to create multimodal DOX@GNR/PSS/HSA NPs. DOX@GNR/PSS/HSA NPs were found to be highly biocompatible and stable in physiological solutions. Furthermore, GNR/PSS/HSA NPs with or without DOX were designed to exhibit strong absorbance in the near-infrared region and high photothermal conversion efficiency. Therefore, bimodal DOX release from DOX@GNR/PSS/HSA NPs could be triggered by an acidic pH and by near-infrared irradiation after NPs preferentially accumulated at tumor sites, leading to a significant chemotherapeutic effect. Moreover, DOX@GNR/PSS/HSA NPs were designed to be applied during chemo- and photo-thermal combination therapy and exhibited a synergistic anticancer effect that was superior to the effect of monotherapy, from both in vitro and in vivo results. These results suggest that DOX@GNR/PSS/HSA NPs are a strong candidate for a nanoplatform for future antitumor therapeutic strategies.

Morphology of reproductive accessory glands in female Sepia pharaonis (Cephalopoda: Sepiidae) sheds light on egg encapsulation.

The pharaoh cuttlefish, Sepia pharaonis, is an important cephalopod fishery species in southeastern Asia, with understudied reproductive physiology. The present study aimed to investigate the cellular characteristics of epithelial cells found in the nidamental glands (NGs) and accessory NGs (ANGs), as well as the structural connections between these two glands in mature female S. pharaonis. A histological analysis revealed two types of epithelial cells in NGs: Alcian blue-positive, PAS-negative mucosubstance-secreting cells and eosinophilic, PAS-positive granule-secreting cells. Using transmission electron microscopy, three types of epithelial cells were identified: cells with electron-dense granules, cells with electron-lucent granules, and cells with both cilia and microvilli in the apex. Mature ANGs contain an abundance of tubular units composed of epithelial cells resting on a thin layer of basal lamina. Innervated muscle cells are tightly adhered to the basal lamina. In addition, we observed epithelial canalization of ANG tubules penetrating through the connective tissue linking NGs and the walls of the tubules in ANGs, which allows the contents of the ANG tubules to be transported to the NGs. Our results suggest that ANGs participate in the encapsulation of the ova via the same pathway as NGs, which provides an important basis for future studies on the mechanism of protection provided by NGs and ANGs during embryonic development in S. pharaonis.

A theranostic micelleplex co-delivering SN-38 and VEGF siRNA for colorectal cancer therapy.

The development of an efficient colorectal cancer therapy is currently a public health priority. In the present work, we proposed a multifunctional theranostic micellar drug delivery system utilizing cationic PDMA-block-poly(ε-caprolactone) (PDMA-b-PCL) micelles as nanocarriers of SN-38 (7-ethyl-10-hydroxycamptothecin), ultra-small superparamagnetic iron oxide nanoparticles (USPIO), and small interfering RNA (siRNA) that targets human vascular endothelial growth factor (VEGF). The VEGF siRNA was conjugated to polyethylene glycol (PEG) (siRNA-PEG) before complexation with the micelles in order to improve the siRNA's stability and to prolong its retention time in the blood circulation. To further improve the in vivo biosafety, we prepared mixed micelles using mPEG-PCL together with PDMA-b-PCL copolymer. The SN-38/USPIO-loaded siRNA-PEG mixed micelleplexes passively targeted to tumor regions and synergistically facilitated VEGF silencing and chemotherapy, thus efficiently suppressing tumor growth via a multi-dose therapy regimen. Additionally, the SN-38/USPIO-loaded siRNA-PEG mixed micelleplexes acted as a negative magnetic resonance imaging (MRI) contrast agent in T2-weighted imaging, resulting in a powerful tool for the diagnosis and for tracking of the therapeutic outcomes. In summary, we established a theranostic micellar drug and gene delivery system that not only synergistically combined gene silencing and chemotherapy but also served as a negative MRI contrast agent, which reveal its potential as a novel colorectal cancer therapy.

Targeting Colorectal Cancer Stem-Like Cells with Anti-CD133 Antibody-Conjugated SN-38 Nanoparticles.

Cancer stem-like cells play a key role in tumor development, and these cells are relevant to the failure of conventional chemotherapy. To achieve favorable therapy for colorectal cancer, PEG-PCL-based nanoparticles, which possess good biological compatibility, were fabricated as nanocarriers for the topoisomerase inhibitor, SN-38. For cancer stem cell therapy, CD133 (prominin-1) is a theoretical cancer stem-like cell (CSLC) marker for colorectal cancer and is a proposed therapeutic target. Cells with CD133 overexpression have demonstrated enhanced tumor-initiating ability and tumor relapse probability. To resolve the problem of chemotherapy failure, SN-38-loaded nanoparticles were conjugated with anti-CD133 antibody to target CD133-positive (CD133(+)) cells. In this study, anti-CD133 antibody-conjugated SN-38-loaded nanoparticles (CD133Ab-NPs-SN-38) efficiently bound to HCT116 cells, which overexpress CD133 glycoprotein. The cytotoxic effect of CD133Ab-NPs-SN-38 was greater than that of nontargeted nanoparticles (NPs-SN-38) in HCT116 cells. Furthermore, CD133Ab-NPs-SN-38 could target CD133(+) cells and inhibit colony formation compared with NPs-SN-38. In vivo studies in an HCT116 xenograft model revealed that CD133Ab-NPs-SN-38 suppressed tumor growth and retarded recurrence. A reduction in CD133 expression in HCT116 cells treated with CD133Ab-NPs-SN-38 was also observed in immunohistochemistry results. Therefore, this CD133-targeting nanoparticle delivery system could eliminate CD133-positive cells and is a potential cancer stem cell targeted therapy.

111In-cetuximab as a diagnostic agent by accessible epidermal growth factor (EGF) receptor targeting in human metastatic colorectal carcinoma.

Colorectal adenocarcinoma is a common cause death cancer in the whole world. The aim of this study is to define the 111In-cetuximab as a diagnosis tracer of human colorectal adenocarcinoma. In this research, cell uptake, nano-SPECT/CT scintigraphy, autoradiography, biodistribution and immunohitochemical staining of EGF receptor were included. HCT-116 and HT-29 cell expressed a relatively high and moderate level of EGF receptor, respectively. The nano-SPECT/CT image of 111In-cetuximab showed tumor radiation uptake of subcutaneous HCT-116 xenograft tumor was higher than SW-620. Autoradiography image also showed that tumor of HCT-116 had high 111In-cetuximab uptake. Mice that bearing CT-26 in situ xenograft colorectal tumors showed similar high uptake in vivo and ex vivo through nano-SPECT/CT imaging at 72 hours. Metastatic HCT-116/Luc tumors demonstrated the highest uptake at 72 hours after the injection of 111In-cetuximab. Relatively, results of 111In-DTPA showed that metabolism through urinary system, especially in the kidney. The quantitative analysis of biodistribution showed count value of metastatic HCT-116/Luc tumors that treated with 111In-cetuximab had a significant difference (P < 0.05) compared with that treated with 111In-DTPA after injection 72 hours. Result of immunohistologic staining of EGF receptor also showed high EGF receptor expression and uptake in metastatic colorectal tumors. In summary, we suggested that 111In-cetuximab will be a potential tool for detecting EGF receptor expression in human metastatic colorectal carcinoma.

Photothermal cancer therapy via femtosecond-laser-excited FePt nanoparticles.

FePt nanoparticles (NPs) have recently been revealed to be significant multifunctional materials for the applications of biomedical imaging, drug delivery and magnetic hyperthermia due to their novel magnetic properties. In this study, a newly discovered photothermal effect activated by the near infrared (NIR) femtosecond laser for FePt NPs was demonstrated. The threshold laser energy to destroy cancer cells was found to be comparable to that of gold nanorods (Au NRs) previously reported. Through the thermal lens technique, it was concluded that the temperature of the FePt NPs can be heated up to a couple of hundreds degree C in picoseconds under laser irradiation due to the excellent photothermal transduction efficiency of FePt NPs. This finding boosts FePt NPs versatility in multifunctional targeted cancer therapy.

Cultural competency in health care and its implications for pharmacy part 3A: emphasis on pharmacy education, curriculums, and future directions.

Culture influences patients' beliefs and behaviors toward health and illness. As the U.S. population becomes more diverse, a critical need exists for pharmacy education to incorporate patient-centered culturally sensitive health care knowledge and skills into the curriculum. Nursing was the first profession to incorporate this type of learning and training into its curriculums, followed by medicine. Pharmacy has also made great progress to revise curriculums, but inconsistency exists in depth, breadth, and methods across pharmacy colleges. This article addresses important aspects of pharmacy education such as curriculum development, incorporation of educational innovations and techniques into the teaching of patient-centered culturally sensitive health care across the curriculum from didactic to experiential learning, assessment tools, and global education. A preliminary model curriculum with objectives and examples of teaching methods is proposed. Future directions in pharmacy education, teaching and learning scholarship, postgraduate education, licensure, and continuing education are also presented.

Cultural competency in health care and its implications for pharmacy Part 3B: emphasis on pharmacy education policy, procedures, and climate.

The Institute of Medicine has stated that greater diversity within health care professionals leads to improved patient outcomes. Therefore, greater diversity within academia and student bodies is required to create future diverse health care professionals. Cultural sensitivity is required from recruitment to physical environment for administrators, faculty, staff, and students. University, college, and department recruitment, search committees, hiring practices, and admissions policies and procedures need to be assessed to determine whether they reflect the applicant pool and patient populations in their regions and whether they are culturally sensitive to a wide variety of cultures. The mission, vision, policies, procedures, curriculums, and environments should also be created or reviewed, modified, and/or expanded to ensure that no administrator, faculty member, staff member, or student is discriminated against or disadvantaged because of cultural beliefs or practices. In addition to discussing the interplay between cultural sensitivity and academic policies, procedures, and environments, this article briefly discusses specific cultural issues related to religion, spirituality, race, ethnicity, gender, age, marital status, veterans, physical, mental, and learning disabilities, and sexual orientation diversity.

In situ real-time investigation of cancer cell photothermolysis mediated by excited gold nanorod surface plasmons.

The photothermolysis of living EMT-6 breast tumor cells triggered by gold nanorods (AuNRs) with two-photon irradiation was conducted in situ and under real-time observation. The morphology and plasma membrane permeability of the cells were key indicators to the phenomena. AuNRs with an aspect ratio of 3.92, and a longitudinal absorption peak at 800 nm were synthesized with a seed-mediated method. The nanorods surfaces were further modified with polystyrenesulfonate (PSS) for biocompatibility. The prepared nanorods displayed excellent two-photon photoluminescence imaging. In situ real-time results revealed cavities internal to the cells were created from thermal explosions triggered by AuNRs localized photothermal effect. The cavitation dynamic is energy dependent and responsible for the perforation or sudden rupture of the plasma membrane. The energy threshold for cell therapy depended significantly on the number of nanorods taken up per cell. For an ingested AuNR cluster quantity N approximately 10-30 per cell, it is found that energy fluences E larger-than 93 mJ/cm(2) led to effective cell destruction in the crumbled form within a very short period. As for a lower energy level E = 18 mJ/cm(2) with N approximately 60-100, a non-instant, but progressive cell deterioration, is observed.