The relationship between palliative radiotherapy and opioid prescribing patterns among patients with metastatic cancer.

BACKGROUND: While randomized trials have established that palliative radiotherapy, especially to bone, can improve qualitative measures of pain, its quantitative relationship to opioid prescribing patterns has remained underexplored. We aimed to identify the association of palliative radiotherapy on opioid prescriptions received among patients with metastatic cancer. METHODS: The Virginia Commonwealth University Institutional Review Board approved retrospective analysis extracted prescription data from all adult patients with metastatic cancer who underwent outpatient palliative external beam radiation therapy at Virginia Commonwealth University Health System from 2008-2018. Institutional prescribing data were used to calculate the average opioid oral morphine milligram equivalent (MME) dose 30, 60 and 90 days both before and after radiotherapy. Univariate and bivariate ordinary least squares (OLS) regression models were used to estimate the relationship of MME changes with clinical, radiation-related, and demographic patient factors. RESULTS: A total of 182 patients met inclusion criteria. Overall, patients required higher opioid doses after radiotherapy, with mean MME 30, 60, and 90 days prior to radiotherapy of 24.6, 20.2, and 16.8 mg, respectively; which increased to 62.9, 77.7 and 82.4 mg post-radiation therapy (P<0.01). Multivariate OLS models predicting the change of MME 60 days pre- and post-radiation treatment showed that younger age and comorbid depression predicted increased MME after radiotherapy. CONCLUSIONS: Patients with metastatic cancer face a relatively high opioid burden, which increases over time, even among those who receive palliative radiation therapy. Patients who are younger and have comorbid depression may have a higher risk of increased opioid burden after radiotherapy.

Community pharmacists in Virginia dispensing naloxone under a standing order: A qualitative study.

BACKGROUND: In 2016, the Virginia Health Commissioner signed a standing order into law allowing licensed pharmacists to dispense opioid receptor antagonists (ORAs) for overdose reversal. OBJECTIVES: Using the theory of planned behavior as an initial guide to study development, the aim of this qualitative study was to explore community pharmacists' attitudes, subjective norm, perceived behavioral control, and behavioral intention toward dispensing ORAs under a standing order in Virginia. METHODS: Semi-structured interviews were conducted with community pharmacists across the Commonwealth between June 2018 and October 2019. Interviews were recorded, transcribed verbatim, and thematically analyzed. RESULTS: Twenty-one community pharmacists were interviewed. Pharmacists were confused about the specifics and the processes involved with dispensing naloxone under the standing order. Furthermore, many recognized the underuse of the standing order. Positive attitudes focused on the life-saving action of ORAs. Negative attitudes included encouraging risky behaviors by patients, negatively affecting the patient-pharmacist relationship, offending or contributing to stigmatizing patrons, and having liability issues to the pharmacy. Subjective norms regarding dispensing of ORAs under the standing order were perceived to be favorable among peer pharmacists and primary care and emergency department physicians but may be seen as profit-seeking by patients. Barriers to service provision included lack of guidance from corporate offices (in chain pharmacies), inadequate training, patient out-of-pocket costs, reimbursement issues, inadequate staffing and time, and stigma. Facilitators comprised the existence of practice site-specific protocols, the REVIVE! training, technician support, increased community awareness, physician collaboration, pharmacist training, and employer guidance. Whereas some pharmacists intended to become more familiarized with the standing order, others did not intend to actively identify patients who were at risk of an opioid overdose. CONCLUSION: Pharmacists expressed mixed behavioral intention toward dispensing ORAs under the standing order. Future research should focus on quantifying the uptake of the standing order at the state level.

Potential cost savings by prevention of adverse drug events with a novel medication review program.

OBJECTIVES: Preventable adverse drug events (ADEs) account for appreciable health care costs and patient morbidity and offer an attractive opportunity for health care providers to improve patient care and decrease costs. It has been suggested that pharmacist intervention can prevent admissions and readmissions due to ADEs. This study assessed the ADEs prevented through a novel medication review program, then estimated the potential cost savings of the prevented ADEs using the literature on cost and prevalence of ADEs that were treated. METHODS: An innovative pharmacist-run medication review was implemented in 2 pharmacies from November 2016 to July 2017. Patients with diabetes, chronic obstructive pulmonary disease, congestive heart failure, prior myocardial infarction, or stroke were included. Pharmacists recorded information about each potential ADE prevented using a standard tracking form which was de-identified and retrospective cost analysis was conducted. Estimates of ADE cost and prevalence requiring treatment were extracted from the literature and incorporated into a model to estimate the potential savings in prevented ADEs overall and per patient. Because ADE costs vary with severity, ADEs in this study were scored for potential severity. RESULTS: This study included 436 patients with a total of 272 likely and 385 likely or possible ADEs identified. ADEs prevented resulted in an estimated total potential savings of $94,832 (sensitivity analysis [SA]: $2261-$828,921) for likely ADEs and $138,914 (SA: $13,520-$264,308) for likely and possible ADEs. Per patient estimated medication review savings were $218 (SA: $5-$1901) for likely ADEs and $319 (SA: $31-$606) for likely and possible ADEs. The benefit of potential cost savings from providing this medication review was 3.6-5.3 times the pharmacists' time and salary cost. CONCLUSIONS: Pharmacists in this study identified a numerous potential ADEs. By intervening to prevent these ADEs, pharmacists could generate substantial cost savings.

Applying educational gaming success to a nonsterile compounding escape room.

BACKGROUND AND PURPOSE: Serious educational gaming success has not been replicated in a nonsterile compounding practical skill-based course. The objective of this study was to create a nonsterile compounding escape room to evaluate third-year professional pharmacy students' (1) knowledge of nonsterile compounding and (2) perceptions of educational escape room gaming utilized in nonsterile compounding. EDUCATIONAL ACTIVITY AND SETTING: The escape room gaming environment used puzzles focused on advanced topics of nonsterile compounding. To evaluate students' knowledge, all participating students completed a pre-assessment and post-assessment mapped to the course objectives. To assess student perceptions of educational escape room gaming, a previously-validated, 12-item survey on student perceptions of educational escape room gaming was modified and administered at the end of the activity. Additional influencing factors such as success in the activity and previous escape room gaming experience were collected. FINDINGS: All thirty students completed the assessments and perception survey (100% response rate). Three out of four student teams successfully escaped the room. Students' knowledge improved or stayed the same for all questions of the assessment questions. Students perceived the escape room as helpful to their learning. Students' increased knowledge and positive perception were independent of their teams' escape success. SUMMARY: Students were actively engaged in learning during a nonsterile compounding escape room. Escape room educational games may be successfully applied to nonsterile compounding to yield increased student knowledge and positive perceptions.

Implementation of an interviewing skills workshop for pharmacy students.

BACKGROUND AND PURPOSE: To describe the implementation and effect of an interviewing skills workshop (ISW) on student confidence on various interviewing techniques. EDUCATIONAL ACTIVITY AND SETTING: A student directed ISW was offered to student pharmacists of all years within the doctor of pharmacy curriculum. There were five stations that student pharmacists rotated through every 12 min: a panel interview, group interview, teleconference interview, video conference interview, and a case station where student pharmacists were given a clinical or ethical case. Stations were staffed by faculty, alumni, and pharmacy residents. Student pharmacists completed a survey directly following the workshop to rate their confidence with the stations prior to and after the activity. Feedback on the activity was solicited from the student pharmacists and those who participated as interviewers. FINDINGS: Twenty-eight student pharmacists participated in the ISW with an 85.7% response rate to the survey (n = 24). All students reported wanting to pursue a career requiring a residency and found the ISW to be beneficial. Average student confidence improved significantly from neutral to confident. Students reported positive themes of feedback and practice while requesting more time for each session and practice with group interviews and ethical situations. Interviewers noted building positive relationships with students and other faculty members. Opportunities for improvement included timing and providing more background information about the student pharmacists. SUMMARY: A student-led ISW was found to be beneficial in improving confidence in student pharmacists. Student pharmacists' confidence increased in all types of interviews and with the clinical case.

Examination of the Link Between Medication Adherence and Use of Mail-Order Pharmacies in Chronic Disease States.

BACKGROUND: Higher medication adherence is associated with positive health outcomes, including reduction in hospitalizations and costs, and many interventions have been implemented to increase patient adherence. OBJECTIVES: To determine whether patients experience higher medication adherence by using mail-order or retail pharmacies. METHODS: Articles pertaining to retail and mail-order pharmacies and medication adherence were collected from 3 literature databases: MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and International Pharmaceutical Abstracts (IPA). Searches were created for each database and articles were compiled. Articles were screened for exclusion factors, and final articles (n=15) comparing medication adherence in patients utilizing mail and retail pharmacies were analyzed. For each study, various factors were identified including days supply, patients' out-of-pocket costs, prior adherence behavior, therapeutic class, measure of adherence, limitations, and results. Studies were then categorized by disease state, and relevant information from each study was compared and contrasted. RESULTS: The majority of studies-14 out of the 15 reviewed-supported higher adherence through the mail-order dispensing channel rather than through retail pharmacies. There are a number of reasons for the differences in adherence between the channels. Study patients who used mail-order pharmacies were more likely to have substantially higher prior adherence behavior, socioeconomic status, and days supply of medicines received and were likely to be offered financial incentives to use mail-order. The few studies that attempted to statistically control for these factors also found that patients using mail-order services were more adherent but the size of the differences was smaller. The extent to which these results indicate an inherent adherence advantage of mail-order pharmacy (as distinct from adherence benefits due to greater days supply, lower copays, or more adherent patients selecting mail-order pharmacies) depends on how well the statistical controls adjusted for the substantial differences between the mail and retail samples. CONCLUSIONS: While the research strongly indicates that consumers who use mail-order pharmacies are more likely to be adherent, more research is needed before it can be conclusively determined that use of mail-order pharmacies causes higher adherence. DISCLOSURES: No outside funding supported this study. Fernandez was partially funded by a Virginia Commonwealth University School of Pharmacy PharmD/PhD Summer Fellowship for work on this project. The authors declare no other potential conflicts of interest. Study concept and design were contributed by Carroll and Fernandez. Fernandez took the lead in data collection, along with Carroll and McDaniel, and data interpretation was performed by Carroll and Fernandez. The manuscript was written and revised by Carroll and Fernandez, with assistance from McDaniel.

Dual targeting of the androgen receptor and hypoxia-inducible factor 1α pathways synergistically inhibits castration-resistant prostate cancer cells.

Enzalutamide is a potent second-generation androgen receptor (AR) antagonist with activity in metastatic castrate-resistant prostate cancer (CRPC). Although enzalutamide is initially effective, disease progression inevitably ensues with the emergence of resistance. Intratumoral hypoxia is also associated with CRPC progression and treatment resistance. Given that both AR and hypoxia inducible factor-1 α (HIF-1α) are key regulators of these processes, dual targeting of both signaling axes represents an attractive therapeutic approach. Crosstalk of the AR and HIF-1α signaling pathways were examined in prostate cancer cell lines (LNCaP, 22Rv1) with assays measuring the effect of androgen and hypoxia on AR-dependent and hypoxia-inducible gene transcription, protein expression, cell proliferation, and apoptosis. HIF-1α inhibition was achieved by siRNA silencing HIF-1α or via chetomin, a disruptor of HIF-1α-p300 interactions. In prostate cancer cells, the gene expression of AR targets (KLK3, FKBP5, TMPRSS2) was repressed by HIF-signaling; conversely, specific HIF-1α target expression was induced by dihydrotestosterone-mediated AR signaling. Treatment of CRPC cells with enzalutamide or HIF-1α inhibition attenuated AR-regulated and HIF-1α-mediated gene transcription. The combination of enzalutamide and HIF-1α inhibition was more effective than either treatment alone. Similarly, the combination also reduced vascular endothelial growth factor protein levels. HIF-1α siRNA synergistically enhanced the inhibitory effect of enzalutamide on cell growth in LNCaP and enzalutamide-resistant 22Rv1 cells via increased enzalutamide-induced apoptosis. In conclusion, the combination of enzalutamide with HIF-1α inhibition resulted in synergistic inhibition of AR-dependent and gene-specific HIF-dependent expression and prostate cancer cell growth.

Prostate cancer progression attributed to autonomic nerve development: potential for therapeutic prevention of localized and metastatic disease.

In a study recently published in Science, Magnon et al. show that both the sympathetic and parasympathetic components of the autonomic nervous system play an integral part in the development and dissemination of prostate cancer (PCa). Inhibition of the sympathetic nervous system (SNS) and disruption of the adrenergic receptors, specifically Ardß 2, resulted in the prevention of primary PCa tumor development in mice. The authors found that inhibition of the SNS is only successful in preventing murine tumor development if completed early enough, and the parasympathetic nervous system (PNS) predominates in later stages of PCa. Inhibition of the PNS by way of the cholinergic receptor, muscarinic 1 (Chrm1), caused mice to develop less metastases to the pelvic lymph nodes, intestines, and bones. A PCa progression scheme has been outlined where initial tumor engraftment is controlled by the SNS but then becomes less prominent than the PNS, which promotes metastasis. The investigators showed the dependence of the autonomic nervous system on development of PCa and present opportunities for prevention; further studies are needed to confirm these results in humans.