Core Entrustable Professional Activities in Clinical Pharmacology for Entering Residency: Common Problem Drugs and How to Prescribe Them.

Although the medical profession strives for safe prescribing, most medications are unique challenges even when prescribed by an experienced provider. In this article we discuss the pitfalls associated with drug interactions between commonly used antibiotics and anticoagulants, the complexities associated with the administration of novel reversible anticoagulants, the often-overlooked severe adverse drug reactions from commonly used classes of medications such as corticosteroids, the nuances of managing an acetaminophen overdose, and uncommon yet serious adverse events associated with the use of contraceptive hormone drugs.

Impact of Federal Regulatory Changes on Clinical Pharmacology and Drug Development: the Common Rule and the 21st Century Cures Act.

The Federal Policy for the Protection of Human Subjects, generally referred to as the "Common Rule," is the basis for the human research protection policies of 16 signatory federal agencies and governs virtually all federally funded research involving humans. The Common Rule was originally published in 1991. It has been recognized that changes to the Common Rule are needed to accommodate changes in the research environment and advances in information technology. The Department of Health & Human Services (HHS) issued an Advance Notice of Proposed Rulemaking in the Federal Register in 2011 and a Notice of Proposed Rulemaking in 2015. The final rule was published on January 19, 2017, just prior to the change in presidential administrations. The long gestation of the new Common Rule reflects the difficulty of obtaining consensus on a number of controversial issues. HHS received more than 2100 public comments on the proposed rule. The revised rule introduces important changes that may be particularly relevant to clinical pharmacology research and drug development. These include: (1) revised informed consent requirements, (2) procedures for "broad consent" to facilitate secondary research use of identifiable private information and/or biological specimens, (3) a mandate to promote review by a single institutional review board (IRB) for oversight of federally funded domestic cooperative research involving multiple institutions, (4) expansion of the categories of exempt research, and (5) removal of the requirement for annual continuing IRB review of research in which the remaining activities are limited to data analysis or accessing clinical follow-up data. Also noteworthy are proposed revisions not included in the final rule, including one to extend the Common Rule to multicenter studies that are not federally funded and one to require informed consent for research use of de-identified biological specimens. Major changes could also be coming for approval of new drugs by the Food and Drug Administration (FDA), although it is not a signatory to the Common Rule. The 21st Century Cures Act, which became law in December 2016, enables faster drug approvals by expanding the kinds of evidence, beyond traditional clinical trials, that the FDA can consider when reviewing new drug applications. For example, the law allows greater use of surrogate markers and data from "real-world experience" to evaluate a drug's efficacy. The Cures Act requires HHS and the FDA to harmonize differences between the Common Rule and FDA regulations for protection of human subjects in research.

Dosage Adjustments Related to Young or Old Age and Organ Impairment.

Differences in physiology related to young or old age and/or organ system impairment alter the absorption, distribution, metabolism, and excretion of many medications and consequently their effectiveness and toxicity. This module discusses common alterations in medication use and dosage that are required in the pediatric age group, in the elderly, and in patients with renal or hepatic disease.

Strategic plan for geriatrics and extended care in the veterans health administration: background, plan, and progress to date.

The leaders of Geriatrics and Extended Care (GEC) in the Veterans Health Administration (VHA) undertook a strategic planning process that led to approval in 2009 of a multidisciplinary, evidence-guided strategic plan. This article reviews the four goals contained in that plan and describes VHA's progress in addressing them. The goals included transforming the healthcare system to a veteran-centric approach, achieving universal access to a panel of services, ensuring that the Veterans Affair's (VA) healthcare workforce was adequately prepared to manage the needs of the growing elderly veteran population, and integrating continuous improvement into all care enhancements. There has been substantial progress in addressing all four goals. All VHA health care has undergone an extensive transformation to patient-centered care, has enriched the services it can offer caregivers of dependent veterans, and has instituted models to better integrate VA and non-VA cares and services. A range of successful models of geriatric care described in the professional literature has been adapted to VA environments to gauge suitability for broader implementation. An executive-level task force developed a three-pronged approach for enhancing the VA's geriatric workforce. The VHA's performance measurement approaches increasingly include incentives to enhance the quality of management of vulnerable elderly adults in primary care. The GEC strategic plan was intended to serve as a road map for keeping VHA aligned with an ambitious but important long-term vision for GEC services. Although no discrete set of resources was appropriated for fulfillment of the plan's recommendations, this initial report reflects substantial progress in addressing most of its goals.

Setting the stage for a new strategic plan for geriatrics and extended care in the Veterans Health Administration: summary of the 2008 VA State of the Art Conference, "The changing faces of geriatrics and extended care: meeting the needs of veterans in the next decade".

The Department of Veterans Affairs (VA) assumed an early leadership role in focusing on care of elderly adults. In 1998, the Federal Advisory Committee on the Future of VA Long-Term Care, appointed by the VA Undersecretary for Health, recommended redirection of VA's extended care programs toward noninstitutional forms. A decade later, VA's Office of Geriatrics and Extended Care (GEC) initiated a strategic planning process by convening experts in geriatrics and health care, policy, and finance in Virginia on March 25 to 27, 2008, to present to VA clinicians and clinical managers the "State of the Art" of VA GEC. Recurring clinical themes included rising numbers and complexity of aging veterans, recent addition of younger veterans to VA's extended care mix, challenges that dementia and mental illness exert throughout GEC, and need for seamlessness in delivery of care across multiple venues. Ongoing research efforts quantifying demand and resources and validating models of care will remain indispensible for meeting clinical challenges. Serious undersupply of clinicians of all disciplines with general or specialty geriatrics knowledge persists. Much of VA's healthcare workforce and leadership are approaching retirement age, driving the need for new educational approaches, recruitment and retention strategies, and innovative delivery systems. Growing dependence on informal caregivers highlights the need for supporting these partners. VA's healthcare budget allocation illustrates how national policy dictates systemic, regional, and local clinical decisions. Rehabilitation of the newest veterans is resulting in systemwide efficiencies. Educating and empowering patients and families results in optimized utilization of health resources.

Enhancing protections for human participants in clinical and health services research: a continuing process.

The authors provide brief information about the Department of Veterans Affairs (VA) and the Veterans Health Administration, to establish an understanding of this large, multifaceted organization. They then offer an overview of the VA's Office of Research and Development, with particular emphasis on recent and ongoing efforts to enhance protection of the rights of human participants in clinical research. The authors discuss various policies and regulations intended to protect human participants in any type of VA research. The protection of human research participants must be a major concern for all researchers. Patients should be well informed about the scope of the research and what their participation entails, and there should be no question as to the voluntariness of their consent. Making sure that these standards are met for each and every veteran who participates in VA research is of the utmost importance.

A First-Line Treatment Option for Elderly Hypertensive Patients: A Low-Dose Multimechanism à -Blocker/Diuretic.

The high incidence of hypertension among the elderly makes a once-daily multimechanism antihypertensive an advantageous agent for the control of hypertension. Because of its safety and efficacy in earlier studies, a low-dose multimechanism à -blocker/diuretic, bisoprolol fumarate 2.5, 5, or 10 mg combined with HCTZ 6.25 mg, was evaluated in multicenter studies, including a subgroup analysis of elderly patients at or above 60 years of age. Results indicate that all 3 dosage strengths of this once-daily agent are effective in reducing blood pressure in this population throughout a 24-hour period. Since low doses of both components are used to achieve efficacy, the incidence of side effects with all 3 dosage strengths is similar to that of placebo. In particular, this agent does not cause hypokalemia. Bisoprolol fumarate/HCTZ is an appropriate therapeutic option for elderly patients with hypertension because of its ability to effectively and safely control blood pressure in this difficult to treat population.