A harmonization effort for acceptable daily exposure application to pharmaceutical manufacturing - Operational considerations.

A European Union (EU) regulatory guideline came into effect for all new pharmaceutical products on June 1st, 2015, and for all existing pharmaceutical products on December 1st, 2015. This guideline centers around the use of the Acceptable Daily Exposure (ADE) [synonymous with the Permitted Daily Exposure (PDE)] and operational considerations associated with implementation are outlined here. The EU guidance states that all active pharmaceutical ingredients (API) require an ADE; however, other substances such as starting materials, process intermediates, and cleaning agents may benefit from an ADE. Problems in setting ADEs for these additional substances typically relate to toxicological data limitations precluding the ability to establish a formal ADE. Established methodologies such as occupational exposure limits or bands (OELs or OEBs) and the threshold of toxicological concern (TTC) can be used or adjusted for use as interim ADEs when only limited data are available and until a more formal ADE can be established. Once formal ADEs are derived, it is important that the documents are routinely updated and that these updates are communicated to appropriate stakeholders. Another key operational consideration related to data-poor substances includes the use of maximum daily dose (MDD) in setting cross-contamination limits. The MDD is an important part of the maximum allowable/safe concentration (MAC/MSC) calculation and there are important considerations for its use and definition. Finally, other considerations discussed include operational aspects of setting ADEs for pediatrics, considerations for large molecules, and risk management in shared facilities.

Issues and approaches for ensuring effective communication on acceptable daily exposure (ADE) values applied to pharmaceutical cleaning.

This manuscript centers on communication with key stakeholders of the concepts and program goals involved in the application of health-based pharmaceutical cleaning limits. Implementation of health-based cleaning limits, as distinct from other standards such as 1/1000th of the lowest clinical dose, is a concept recently introduced into regulatory domains. While there is a great deal of technical detail in the written framework underpinning the use of Acceptable Daily Exposures (ADEs) in cleaning (for example ISPE, 2010; Sargent et al., 2013), little is available to explain how to practically create a program which meets regulatory needs while also fulfilling good manufacturing practice (GMP) and other expectations. The lack of a harmonized approach for program implementation and communication across stakeholders can ultimately foster inappropriate application of these concepts. Thus, this period in time (2014-2017) could be considered transitional with respect to influencing best practice related to establishing health-based cleaning limits. Suggestions offered in this manuscript are intended to encourage full and accurate communication regarding both scientific and administrative elements of health-based ADE values used in pharmaceutical cleaning practice. This is a large and complex effort that requires: 1) clearly explaining key terms and definitions, 2) identification of stakeholders, 3) assessment of stakeholders' subject matter knowledge, 4) formulation of key messages fit to stakeholder needs, 5) identification of effective and timely means for communication, and 6) allocation of time, energy, and motivation for initiating and carrying through with communications.

Communication and outcomes of visits between older patients and nurse practitioners.

BACKGROUND: Effective patient-clinician communication is at the heart of good healthcare and may be even more vital for older patients and their nurse practitioners (NPs). OBJECTIVES: The objectives of this study were to examine 1)contributions of older patients' and NPs' characteristics and the content and relationship components of their communication to patients' proximal outcomes (satisfaction and intention to adhere) and longer term outcomes (changes in presenting problems, physical health, and mental health), and 2) contributions of proximal outcomes to longer term outcomes. METHODS: Visits were video-recorded for a statewide sample of 31 NPs and 155 older patients. Patients' and NPs' communications during visits were measured using the Roter Interaction Analysis System for verbal activities, a check sheet for nonverbal activities, and an inventory of relationship dimension items. Proximal outcomes were measured with single items after visits. At 4 weeks, change in presenting problems was measured with a single item, and physical and mental health changes were measured with the SF-12 Version 2 Health Survey. Mixed-model regression with backward deletion was conducted until only predictors with p

Alliance not compliance: coaching strategies to improve type 2 diabetes outcomes.

PURPOSE: To explore strategies for improving patient outcomes in type 2 diabetes. DATA SOURCES: The literature related to type 2 diabetes management, behavior change, communication, diabetes self-management, and coaching. CONCLUSIONS: The strategies currently suggested for improving patient outcomes, e.g., increasing provider adherence to evidence-based management guidelines, streamlining practice systems, and promoting patient lifestyle changes through intensive education, have produced mixed outcomes. Of the many complexities involved in managing type 2 diabetes, motivating patients to change behavior may be the most challenging. A suggestion for improving patient self-management of type 2 diabetes is to use coaching communication within a framework of behavior change in the context of the primary care encounter between nurse practitioners (NPs) and their patients. IMPLICATIONS FOR PRACTICE: Given the varied outcomes of current strategies, coaching by NPs may provide a feasible alternative for improving patient outcomes in type 2 diabetes. Coaching communication can be implemented during office visits as an intervention without cost. To effectively implement this approach, however, practicing NPs and NP students need more formal education in this expected but underdeveloped NP role competency. NPs are called upon to contribute to the body of knowledge needed to validate the merits of coaching for their patients.

From the sidelines: coaching as a nurse practitioner strategy for improving health outcomes.

PURPOSE: The purposes of this study were to explore coaching as a nurse practitioner (NP) strategy for improving patient health outcomes and to lay a foundation for validating coaching benefits. DATA SOURCES: Review of coaching literature in psychology, sports, business, and nursing. CONCLUSIONS: Coaching has been reported as successful in psychology, sports, business, and more recently nursing, for assisting people to achieve goals that are important to them. Coaching may be very effective in encouraging, inspiring, and empowering patients to reach their maximum health potential, particularly if lifestyle change is required; however, coaching research is in its early stages. Coaching is not well defined, so claims of coaching benefits must be viewed cautiously. Coaching is an expected NP role competency, but it is not well explicated in the literature. Defining the concept of coaching from multidisciplinary consensus, expanding knowledge of the coaching process, and consciously implementing coaching communication in the NP/patient primary care encounter may result in measurable outcomes that demonstrate coaching effectiveness. IMPLICATIONS FOR PRACTICE: Coaching fits well with the holistic, collaborative approach to patient care which NPs value. Coaching provides an opportunity to shift traditional thinking about patient/provider relationships and how to motivate patients toward behavior change. The challenge for NPs is to take the time to learn the coaching process, employ coaching communication strategies in the primary care encounter, and engage in research that measures coaching effectiveness.

Nurse practitioners and managed care: patient satisfaction and intention to adhere to nurse practitioner plan of care.

PURPOSE: To explore patient satisfaction, intention to adhere to nurse practitioner (NP) plan of care, and the impact of managed care on NPs' patients in multiple settings, the final phase of a three-part study of NPs and managed care. DATA SOURCES: Postvisit questionnaires and narrative comments about patient satisfaction with NP communication, overall satisfaction with visit, recall of plan of care, intention to adhere to NP's recommendations, and impact of managed care on ease of obtaining healthcare resources. CONCLUSIONS: Patients were very satisfied with NP communication and with their healthcare visit. They mostly intended to adhere to the NP-recommended plan of care but less so to recommended lifestyle changes. Patients trusted their NPs, valued their expertise, were confident in the NPs' care, and believed that the NPs considered their best interests. They appreciated that the NPs took time to listen to their concerns and helped them to obtain healthcare resources. Most patients were not greatly impacted by managed care and obtained needed healthcare resources with little difficulty. IMPLICATIONS FOR PRACTICE: Although the first two phases of this study found that many NPs had strong negative attitudes toward managed care, these attitudes were not conveyed toward patients in this sample. NPs, however, will continue to face new challenges as third-party payers attempt to reduce healthcare costs, further testing NP adaptability and resourcefulness.

Embattled and embittered or empowered and evolving: nurse practitioner attitudes toward managed care.

PURPOSE: To explore the attitudes of nurse practitioners (NPs) toward managed care and to identify the sources of negative attitudes and the factors that may ameliorate them. DATA SOURCES: NPs, members of the Massachusetts Coalition of NPs, participated in in-depth interviews about the impact of managed care on their practice. CONCLUSIONS: The sources of NP negativity about managed care for many study participants lay in their not appreciating the importance of the business aspects of practice and the provider's role in controlling healthcare costs, reluctance to work with what they perceived as a rigid "system," and lack of support for them to navigate it. They felt pressured by productivity issues, time constraints, practice restrictions, and documentation demands associated with reimbursement. Those who sustained a more positive attitude were realistic about healthcare economics, were willing and able to negotiate the system, were creative and flexible, and felt empowered by knowledge of the business of practice. Some NPs, however, chose to work in practices where they did not feel as pressured as their counterparts in large, busy primary care practices. IMPLICATIONS FOR NP PRACTICE AND EDUCATION: Understanding experiences that have influenced NP attitudes regarding managed care may assist NP faculty to better prepare NP students for their future roles. NPs must be able to challenge, yet be part of, an evolving system that promotes cost-effective health care for everyone, which was what managed care originally was intended to do.

Promoting nurse practitioner practice through research: opportunities, challenges, and lessons.

PURPOSE: To discuss the opportunities derived, challenges faced, and lessons learned in the research process, including recruiting and retaining nurse practitioner (NP) participants, obtaining institutional approval, and solving research team issues in a National Institutes of Health/National Institute of Nursing Research (NIH/NINR)-funded study of communication between NPs and their older patients in managed care and non-managed care settings. DATA SOURCES: The video-taped interactions between 30 NPs and 150 patients, research team experiences in conducting the research, and a review of relevant literature. CONCLUSIONS: Key factors in NP study participation included recognizing the importance of research in demonstrating the effectiveness of the NP role and for advancing the profession, having participated in previous research, enjoying the research process, employer incentives, membership in NP professional organizations, relationships with the university and the school of nursing conducting the research, and knowledge of the coinvestigator's work. NP recruitment was facilitated by word of mouth, professional organization assistance, and articles in a widely distributed, free nursing journal. Data collection was significantly delayed by attrition of NP participants, logistical problems with scheduling and travel, and varied approval procedures by Institutional Review Boards (IRBs) at study sites. The pace of nursing research could be much more efficient if IRB processes involved fewer bureaucratic entanglements. Preliminary study findings, however, show positive outcomes for older patients after NP care. IMPLICATIONS FOR PRACTICE: To demonstrate positive patient outcomes and move the NP profession forward, NPs must be willing to commit to participation in research on their effectiveness as providers in today's healthcare environment.

Human pharmaceuticals in US surface waters: a human health risk assessment.

The detection of low levels of pharmaceuticals in rivers and streams, drinking water, and groundwater has raised questions as to whether these levels may affect human health. This report presents human health risk assessments for 26 active pharmaceutical ingredients (APIs) and/or their metabolites, representing 14 different drug classes, for which environmental monitoring data are available for the United States. Acceptable daily intakes (ADIs) are derived using the considerable data that are available for APIs. The resulting ADIs are designed to protect potentially exposed populations, including sensitive sub-populations. The ADIs are then used to estimate predicted no effect concentrations (PNECs) for two sources of potential human exposure: drinking water and fish ingestion. The PNECs are compared to measured environmental concentrations (MECs) from the published literature and to maximum predicted environmental concentrations (PECs) generated using the PhATE model. The PhATE model predictions are made under conservative assumptions of low river flow and no depletion (i.e., no metabolism, no removal during wastewater or drinking water treatment, and no instream depletion). Ratios of MECs to PNECs are typically very low and consistent with PEC to PNEC ratios. For all 26 compounds, these low ratios indicate that no appreciable human health risk exists from the presence of trace concentrations of these APIs in surface water and drinking water.

Screening analysis of human pharmaceutical compounds in U.S. surface waters.

The PhATE (Pharmaceutical Assessment and Transport Evaluation) model presented in this paper was developed as a tool to estimate concentrations of active pharmaceutical ingredients (APIs) in U.S. surface waters that result from patient use (or consumption) of medicines. PhATE uses a mass balance approach to model predicted environmental concentrations (PECs) in 11 watersheds selected to be representative of most hydrologic regions of the United States. The model divides rivers into discrete segments. It estimates the mass of API that enters a segment from upstream or from publicly owned treatment works (POTW) and is subsequently lost from the segment via in-stream loss mechanisms or flow diversions (i.e., man-made withdrawals). POTW discharge loads are estimated based on the population served, the API use per capita, the potential loss of the compound associated with human use (e.g., metabolism), and the portion of the API mass removed in the POTW. Simulations using three surrogate compounds showthat PECs generated by PhATE are generally within an order of magnitude of measured concentrations and that the cumulative probability distribution of PECs for all watersheds included in PhATE is consistent with the nationwide distribution of measured concentrations of the surrogate compounds. Model simulations for 11 APIs yielded four categories of results. (1) PECs fit measured data for two compounds. (2) PECs are below analytical method detection limits and thus are consistent with measured data for three compounds. (3) PECs are higher than (i.e., not consistent with) measured data for three compounds. However, this may be the consequence of as yet unidentified depletion mechanisms. (4) PECs are several orders of magnitude below some measured data but consistentwith most measured data forthree compounds. For the fourth category, closer examination of sampling locations suggests that the field-measured concentrations for these compounds do not accurately reflect human use. Overall, these results demonstrate that PhATE may be used to predict screening-level concentrations of APIs and related compounds in the environment as well as to evaluate the suitability of existing fate information for an API.

Nurse practitioner self-confidence and attitudes regarding managed care.

PURPOSE: To examine the relationship between nurse practitioner (NP) perceived self-confidence in performing managed care tasks and NP attitudes toward managed care. DATA SOURCES: A random sample of NPs--members of the Massachusetts Coalition of Nurse Practitioners--completed a demographic survey, responded to questions measuring self-confidence in performing managed care tasks and attitudes toward managed care, and wrote about their managed care experiences. CONCLUSIONS: NPs were only moderately confident in performing managed care tasks and had mostly negative attitudes toward managed care. They reported intense frustration related to prescriptive coverage and referrals to specialty services, potential trust issues between providers and patients, and ethical and legal dilemmas in tailoring plans of care to fit the patient's insurance. The NPs' written comments indicate a need for more in-depth exploration of NP attitudes toward managed care. IMPLICATIONS FOR PRACTICE AND EDUCATION: Continuing education in selected managed care competencies, better education of NP students, and promotion of organizational cultures that support interdisciplinary teamwork as well as population- and evidence-based practice may help NPs to embrace the promise of managed care and to offer solutions to its problems.

Impact of war on American adolescents.

PROBLEM: The impact of the Persian Gulf war on adolescents in Columbia, Charleston, and Sumter, SC. METHODS: Four semiannual surveys measured adolescents' exposure to and evaluations of the Persian Gulf war, and the relationship between this exposure and mental distress. FINDINGS: Of the sample, 814 (65.9%) reported being distressed by the war and 849 (69%) reported feeling better after the war ended. More than half the sample had a friend or relative sent to the war (n = 725, 58.8%), and of these, 458 were African American. Nine percent (n = 111) of the sample had a mother, father, or both a mother and a father in the war. CONCLUSIONS: There was a positive correlation between adolescents' ratings on the Negative Impact of War Scores and Mental Distress Scores despite the easy victory and public support for the war in the United States. Females and African Americans viewed the war more negatively than did Caucasian males.

A strategy to reduce the numbers of fish used in acute ecotoxicity testing of pharmaceuticals.

The pharmaceutical industry gives high priority to animal welfare in the process of drug discovery and safety assessment. In the context of environmental assessments of active pharmaceutical ingredients (APIs), existing U.S. Food and Drug Administration and draft European regulations may require testing of APIs for acute ecotoxicity to algae, daphnids, and fish (base-set ecotoxicity data used to derive the predicted no-effect concentration [PNECwater] from the most sensitive of three species). Subject to regulatory approval, it is proposed that testing can be moved from fish median lethal concentration (LC50) testing (typically using > or = 42 fish/API) to acute threshold tests using fewer fish (typically 10 fish/API). To support this strategy, we have collated base-set ecotoxicity data from regulatory studies of 91 APIs (names coded for commercial reasons). For 73 of the 91 APIs, the algal median effect concentration (EC50) and daphnid EC50 values were lower than or equal to the fish LC50 data. Thus, for approximately 80% of these APIs, algal and daphnid acute EC50 data could have been used in the absence of fish LC50 data to derive PNECwater values. For the other 18 APIs, use of an acute threshold test with a step-down factor of 3.2 is predicted to give comparable PNECwater outcomes. Based on this preliminary scenario of 91 APIs, this approach is predicted to reduce the total number of fish used from 3,822 to 1,025 (approximately 73%). The present study, although preliminary, suggests that the current regulatory requirement for fish LC50 data regarding APIs should be succeeded by fish acute threshold (step-down) test data, thereby achieving significant animal welfare benefits with no loss of data for PNECwater estimates.

Challenge and opportunity: nurse practitioner programs partnering with managed care.

PURPOSE: To examine the experiences of nurse practitioner (NP) students who participated in a collaborative educational program between the University of Massachusetts, Amherst, and Health New England (HNE) Health Plan, Springfield, MA. Nurse practitioner faculty and managed care executives shared resources to educate NP students and to address their perceptions about managed care. DATA SOURCES: Verbatim transcriptions and journal writings of students specifically designated as "Partnerships for Quality Education (PQE) trainees" and reports of their fellow classmates, all of whom received varying extent of access to managed care theory, administrative, and clinical experiences within the HNE plan. CONCLUSIONS: The experiences of the PQE trainees revealed a greatly expanded understanding of managed care that challenged students' previous beliefs. They reported greater satisfaction with program participation than their classmates, had an unprecedented opportunity to articulate the NP role to a managed care organization (MCO), and learned that a collaborative, rather than an adversarial, relationship with an MCO produces better outcomes for patients and providers. Many students in the class, including some of the PQE trainees, were concerned, however, about what they perceived as managed care "taking time away from clinical issues," which they considered more important. IMPLICATIONS FOR TEACHING AND PRACTICE: There is a need for balance between both managed care and clinical content in NP programs, yet students must have an intimate grasp of both if they are to survive in today's health care environment.

The master's portfolio: validating a career in advanced practice nursing.

PURPOSE: To describe the process of portfolio development and faculty review that offers graduate credit within a framework of structural empowerment and mentoring for documented educational and clinical accomplishments for family nurse practitioners (FNPs). DATA SOURCES: Selected literature and examples from one student's portfolio to illustrate the process. CONCLUSIONS: The degree granting process assists certified FNPs to fulfill career aspirations through achieving graduate level education at the University of Massachusetts, Amherst, School of Nursing. IMPLICATIONS FOR PRACTICE: The portfolio process affords practicing FNPs not only the opportunity to acquire an advanced degree but a framework for examining and validating a career. For the student in this exemplar, it was a "significant, introspective, satisfying learning experience," a rare opportunity in a busy professional life.