A Problem in NIH and Federally Funded Prostate Cancer Interventional Clinical Trials.

BACKGROUND: Obesity, diagnosed in 41.1% of African American (AA) men, is a risk factor for prostate cancer (PCa) recurrence, progression, and increased mortality. Obesity is associated with aggressive PCa only in AA men and not White American (WA) men. The overall health of AA PCa patients is also more likely to be adversely affected by comorbid type 2 diabetes (T2D), often an outcome of obesity and a cause of reduced odds of PCa survival. This evidence suggests that preventing and controlling comorbid obesity and T2D in AA men diagnosed with PCa should be a research funding priority. AIM: The aim of this study is to determine if federally funded PCa clinical trials controlled T2D and obesity. METHODS: Completed interventional PCa clinical trials conducted in the USA, funded by the NIH or other federal agency, which included males aged 18-64 years, and reported study protocols were included in the study. We examined the intervention modalities used in the trials to determine if any attempted to control obesity and T2D. RESULTS: Fifty-eight trials met the study inclusion criteria. Of these 11 were excluded from the analysis as they did not report AA men. A total of 5802 men participated in the remaining 47 trials. Of these, 917 (15.8%) were AA and 4885 (84.2%) were WA men. Forty (85.1%) trials used pharmaceutical medication therapies or other clinical procedures. None of the medications or clinical procedures used were indicated for treatment of obesity and T2D. 5 (10.6%) trials addressed treatment preferences, survivorship, coping, function, and incontinence among PCa patients. Only 2 (4.25%) trials examined weight loss and diet. CONCLUSIONS: None of the completed federally funded PCa clinical trials that included AA men used methods to control T2D. Only an insignificant number (4.25%) attempted to control obesity. This gap in therapeutic optimization to control these comorbid conditions indicates a critical area in need of federal funding priority.

Inclisiran: A First-in-Class siRNA Therapy for Lowering Low-Density Lipoprotein Cholesterol.

OBJECTIVE: To review the current pharmacology, pharmacokinetics/pharmacodynamics, safety, and efficacy of inclisiran in lowering lipid levels. DATA SOURCES: A PubMed (from December 1, 2014 to April 15, 2022) and ClinicalTrials.gov search was conducted using ALN-PCSsc, ALN-60212, PCSK9si KJX-839, and inclisiran. Additional articles were identified by hand from references. STUDY SELECTION AND DATA EXTRACTION: We included English-language articles evaluating inclisiran pharmacology, efficacy, or safety in humans for lowering low-density lipoprotein cholesterol (LDL-C). DATA SYNTHESIS: Inclisiran is a novel small interfering RNA-based therapy administered as a twice-yearly subcutaneous injection. By binding to the messenger RNA (mRNA) precursor of proprotein convertase subtilisin/kexin type 9 (PCSK9), inclisiran inhibits expression of the PCSK9 gene, resulting in increased recycling and expression of LDL receptors and decreased levels of LDL-C. Like PCSK9 inhibitors, inclisiran was associated with a comparable extent of LDL-C reduction in several phase II/III trials. Compared with placebo, inclisiran was found to have similar adverse events except for injection-site reaction. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Currently, inclisiran lacks data on clinical outcome improvement or long-term safety. However, it may play a role in patients with atherosclerotic cardiovascular disease (ASCVD) or ASCVD risk equivalent if optimal LDL-C cannot be achieved by statins and PCSK9 inhibitors cannot be tolerated. The drug may be used for heterozygous familial hypercholesterolemia. CONCLUSION: Inclisiran is an effective and safe medication for lowering LDL-C levels. Additional data regarding efficacy on cardiovascular outcomes and long-term safety profile with inclisiran are needed.

An ethics-based approach to global health research part 4: Scholarship and publications.

Disseminating research findings from global health collaborations is essential to advancing science. However, there are a number of ethical considerations and potential challenges to address to ensure thoughtful and non-exploitative reporting. The factors include the benefits and risks to publication, authorship criteria or values, and the accessibility of forums or journals in which to pursue publication. This paper provides commentary related to planning for writing, communicating intentions to publish, obtaining permissions to publish, risks in internationally collaborative work, authorship principles, and journal selection. Authors' and editors' knowledge of experienced individuals from both pharmacy literature, medical fields, and general publications is incorporated to provide an assessment of risks and benefits of publication of international global health research.

An ethics-based approach to global health research part 1: Building partnerships in global health.

Global health partnerships (GHPs) can be the cornerstone for advancing research and public health. The steps to build a global research partnership focus on sharing a common research agenda, identifying key partners in the community, and establishing goals and expectations for partnerships. Moreover, upholding important values, such as communication, trust, and transparency is essential for building successful partnerships. Ethical dilemmas can propose challenges to researchers in global health. These challenges can be overcome by creating a shared vision for a research agenda, maintaining communication, and providing bidirectional training.

An Ethics-based Approach to Global Health Research Part 2: Strategies for Overcoming Logistic and Implementation Challenges.

With the growth of global pharmacy partnerships and collaborative research, particularly between high-income countries and low- or middle-income countries, it is necessary to establish best practices for fair and ethical collaboration and research. There is a gap in the pharmacy literature in this regard. Through this commentary, authors will present a pathway for future global health researchers including generating ideas based on mutual needs of the partnership and the community; exploring the importance of regulations including the need to conduct research and partnership projects within the confines of each participant's professional scope of practice, expertise, and licensure; describing the need to develop agreements and the components that should be included in such an agreement; discussing ethical guidelines for research planning, obtaining ethical approval, and planning for adverse events; and illustrating ethical considerations for research implementation with considerations around consent, data collection, linking patients to care after the completion of the study, and dissemination. Global examples, with a pharmacy-specific approach where applicable, within each section highlight the importance of discussion and action around ethics and equity when pursuing collaborative research, recognizing that many of these situations involve difficult decisions.

An Ethics-based approach to Global Health Research Part 3: Emphasis on Partnership Funding.

Acquiring funding for global health research within pharmacy can be challenging, particularly for new investigators who may have a strong interest in resolving global dilemmas related to health. Moreover, there can be inherent imbalances and ethical issues when navigating the funding process for global partnerships. There exists a lack of literature providing ethical guidance for mitigating dilemmas that may arise. This commentary discusses current funding streams for investigators interested in global pharmacy research, as well as specific recommendations for the funding process. These recommendations include managing award funds, ethical considerations for funding research partnerships, and balancing power between low to middle income countries and high-income countries. Lastly, case examples of funding partnerships involving pharmacy are highlighted, emphasizing important lessons learned. This commentary addresses the critical need for providing global health researchers with both important considerations and experience-based recommendations for navigating global funding partnerships using an ethical approach.

Tafamidis: A First-in-Class Transthyretin Stabilizer for Transthyretin Amyloid Cardiomyopathy.

Objective: To review the pharmacology, efficacy, and safety of the selective transthyretin inhibitor tafamidis for transthyretin amyloid cardiomyopathy (ATTR-CM). Data Sources: A PubMed (1966 to October 2019) and ClinicalTrials. gov search was conducted using the keywords tafamidis, Fx-1006A, Vyndaqel, and Vyndamax. Additional articles were identified from references. Study Selection and Data Extraction: We included English-language clinical studies evaluating the pharmacology, efficacy, or safety of tafamidis in humans for ATTR-CM. Data Synthesis: Tafamidis binds to the thyroxine-binding sites of the transthyretin tetramer and inhibits its dissociation into monomers, which is the rate-limiting step in the amyloidogenic process. Treatment with tafamidis was significantly associated with a significant reduction in mortality, lowered cardiovascular-related hospitalizations, less functional decline, and improved transthyretin stabilization compared with placebo. Additionally, tafamidis was found to have fewer adverse events, with no difference found compared with placebo. Relevance to Patient Care and Clinical Practice: Historically, symptomatic management for ATTR-CM was the only option, and the treatment of the underlying disease was limited to liver or heart transplantation. Tafamidis is the first medication approved for the treatment of ATTR-CM and the only medication that showed a reduction in all-cause mortality and cardiovascular-related hospitalizations in patients with amyloidosis. However, the role of tafamidis in patients with the New York Heart Association class III/IV heart failure or mutated transthyretin remains unclear. Conclusion: Tafamidis is an effective and safe oral medication for the treatment of the cardiomyopathy of transthyretin-mediated amyloidosis in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization.

The Effect of Ranolazine on Glycemic Control: a Narrative Review to Define the Target Population.

Ranolazine is an anti-anginal medication that reduces the sodium-dependent calcium overload via the inhibition of the late sodium current. After its approval for the treatment of chronic angina in 2006 in the USA, ranolazine has been reported to have several pleiotropic effects on various cardiac conditions, such as atrial fibrillation, ventricular arrhythmias, diastolic and microvascular dysfunction, and pulmonary arterial hypertension. Recently, several studies reported some promising results on the potential benefits of ranolazine on glycemic control. Though the mechanism of the antihyperglycemic effect is still unknown, ranolazine may exert the effect through ß cell preservation, inhibition of glucose secretion, and enhancement of insulin secretion in a glucose-dependent manner. Given the increased risk of cardiovascular disease in patients with diabetes, it will be useful if one medication can simultaneously improve chronic angina and diabetes. Therefore, ranolazine could be a favored choice among other anti-anginal agents for patients with comorbidity of chronic angina and diabetes mellitus. In this review, we summarize the available data from clinical studies and provide valuable insight into defining the target population for the antihyperglycemic effect of ranolazine.

Extended Duration Dual Antiplatelet Therapy After Percutaneous Coronary Intervention in Patients With Peripheral Arterial Disease: A Meta-Analysis.

BACKGROUND: Patients with peripheral arterial disease (PAD) undergoing percutaneous coronary intervention (PCI) are at elevated risk of ischemic and bleeding events. However, the optimal duration of dual antiplatelet therapy (DAPT) after PCI in patients with PAD remains unclear. METHODS: A systematic literature search was performed through June 2017 using PubMed, EMBASE and Cochrane databases with the following key terms: "dual antiplatelet therapy", "P2Y12 inhibitor", "myocardial infarction", "percutaneous coronary intervention", "stent", "peripheral arterial disease", and "ankle-brachial index". The analysis was restricted to randomized trials published in English in patients with PAD receiving extended DAPT (> 12-month) after PCI. Overall analysis was performed using Review Manager 5.3 with the Mantel-Haenszel method. RESULTS: Two randomized controlled trials involving 895 patients were included in this review. Compared to the placebo group, there was no statistical significance in the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) in patients receiving extended DAPT (odds ratio (OR) 0.76, 95% confidence interval (CI) 0.37 - 1.57; P = 0.46). The results were associated with substantial heterogeneity (I2 = 71%, P = 0.07). Extended DAPT was not significantly associated with increased moderate/severe bleeding events (OR 1.63, 95% CI 0.84 - 3.18; P = 0.15; I2 = 0%, P = 0.59). The extended DAPT was associated with 82% relative risk reduction in the events of definite/probably stent thrombosis. CONCLUSIONS: Among patients with PAD, extended DAPT after PCI resulted in a non-significant difference in ischemic and bleeding events compared to placebo, respectively. The routine use of extended DAPT in this cohort should be carefully evaluated.

Current Practices in Global/International Advanced Pharmacy Practice Experiences: Preceptor and Student Considerations.

The objective of this article is to describe the key areas of consideration for global/international advanced pharmacy practice experience (G/I APPE) preceptors, students and learning objectives. At the 2013 Annual Meeting of the American Association of Colleges of Pharmacy (AACP), the GPE SIG prepared and presented an initial report on the G/IAPPE initiatives. Round table discussions were conducted at the 2014 AACP Annual Meeting to document GPE SIG member input on key areas in the report. Literature search of PubMed, Google Scholar and EMBASE with keywords was conducted to expand this report. In this paper, considerations related to preceptors and students and learning outcomes are described. Preceptors for G/I APPEs may vary based on the learning outcomes of the experience. Student learning outcomes for G/I APPEs may vary based on the type of experiential site. Recommendations and future directions for development of G/IAPPEs are presented. Development of a successful G/I APPE requires significant planning and consideration of appropriate qualifications for preceptors and students.

Current Practices in Global/International Advanced Pharmacy Practice Experiences: Home/Host Country or Site/Institution Considerations.

International outreach by schools and colleges of pharmacy is increasing. In this paper, we provide current practice guidelines to establish and maintain successful global/international advanced pharmacy practice experiences (G/I APPEs) with specific recommendations for home/host country and host site/institution. The paper is based on a literature review (2000-2014) in databases and Internet searches with specific keywords or terms. Educational documents such as syllabi and memoranda of understanding (MoUs) from pharmacy programs were also examined. In addition, a preliminary draft was developed and the findings and recommendations were reviewed in a 90-minute roundtable discussion at the 2014 American Association of Colleges of Pharmacy Annual Meeting. Recommendations for the host country include travel considerations (eg, passport, visa, air travel), safety, housing, transportation, travel alerts and warnings, health issues, and financial considerations. For the home country, considerations for establishment of G/I APPE site (eg, vetting process, MoU, site expectations) are described. The paper is a resource for development of new G/I APPEs and provides guidance for continuous quality improvement of partnerships focusing on G/I pharmacy education.