The ADAPT online education program: A tool for practicing pharmacists delivering patient-centered care.

OBJECTIVES: The ADapting pharmacists' skills and Approaches to maximize Patient's drug Therapy effectiveness (ADAPT) e-learning program was developed by a consortium of Canadian pharmacy educators and researchers to prepare practicing pharmacists for patient-centered care. We selected this education program to provide training for pharmacists as the workforce transformation component of a Center for Medicare and Medicaid Innovation project. In this report we share our experiences with this educational program. SETTING: Online educational program. PRACTICE DESCRIPTION: ADAPT presents a standard approach to medication assessment, team collaboration, patient assessment, evidence-based decision making, and documentation. PRACTICE INNOVATIONS: ADAPT was used to prepare practicing pharmacists for new roles in direct patient care in patient-centered medical homes. EVALUATION: Participants were surveyed at the midpoint and end of the program to determine its impact on their confidence in providing patient-centered care and to elicit feedback about their perceptions of the program. Participants completed written action plans for each module that included their reflections on the course material and the skills they desired to implement in practice. Descriptive statistics were used to analyze Likert-type questions, and a content analysis was performed to analyze responses to open-ended questions and action plan responses. RESULTS: Two pharmacist cohorts completed the 20-week program from October 2012 to March 2013 (n = 13) and from August 2013 to January 2014 (n = 10). Pharmacists' perceived that their confidence in providing patient-centered care improved for all modules. Almost all pharmacists reported improved confidence in patient interviewing (89%), documentation (88%), and collaboration skills (83%). The content analysis identified the modules on interviewing and documentation as the most valuable and likely to result in changes to the pharmacists' practice. The opportunity to learn from colleagues was cited as a strength of the program. CONCLUSION: The ADAPT educational program provided pharmacists with the tools necessary to deliver patient-centered care in ambulatory care settings.

Improvements in MBD lab outcomes associated with improved pharmaceutical care in hemodialysis patients.

End stage renal disease (ESRD) patients require a large number of medications and are known to have high rates of nonadherence. It is estimated that >50% of ESRD patients do not take their phosphate binders as prescribed. The renal pharmacy FreseniusRx provides coordinated ESRD medication delivery and adherence support for enrolled patients. We investigated whether coordinated pharmacy care of mineral and bone disorder (MBD) therapies is associated with improvements in laboratory. outcomes. We used data from hemodialysis patients treated at Fresenius Medical Care North America (FMCNA) clinics from February 2014 to January 2015. We included patients who were residing in a state with >100 patients in the FMCNA network, not in a nursing home, and prescribed a phosphate binder and/or calcimimetic. We found 15,287 pharmacy patients who met the study criteria. Concurrent control patients not in the pharmacy were matched to pharmacy patients on a monthly basis that was based off the first date of receipt of therapy from FreseniusRx using 1:1 nearest neighbor matching on the logit of the propensity score for an array of clinical and non-clinical parameters. Logistic regression was used to measure the association between pharmacy care and patients achieving their laboratory goals for phosphorus (PO4) and intact parathyroid hormone (iPTH), and combined goals for total calcium (Ca), PO4, and iPTH. We analyzed data from 30,574 patients (15,287 pharmacy and control). In unadjusted and adjusted analyses, we consistently observed that pharmacy patients were more likely to achieve their MBD laboratory goals as compared to controls. In an adjusted analysis, we found pharmacy patients were more likely to achieve their MBD laboratory targets at 3, 6, 9, and 12 months for PO4 (11.1%, 10.5%, 11.8% and 12.7% respectively), iPTH (8.9%, 17.5%, 23.4% and 27.9% respectively) and combined goals for Ca, PO4, and. iPTH (12.1%, 13.4%, 16.7% and 21.2% respectivelv) versus controls (n<0.01 for all comparisons). These findings indicate that coordinated pharmaceutical care may be associated with improvements in patients achieving their MBD laboratory goals.

Interactive preventive health record to enhance delivery of recommended care: a randomized trial.

PURPOSE: Americans receive only one-half of recommended preventive services. Information technologies have been advocated to engage patients. We tested the effectiveness of an interactive preventive health record (IPHR) that links patients to their clinician's record, explains information in lay language, displays tailored recommendations and educational resources, and generates reminders. METHODS: This randomized controlled trial involved 8 primary care practices. Four thousand five hundred patients were randomly selected to receive a mailed invitation to use the IPHR or usual care. Outcomes were measured using patient surveys and electronic medical record data and included IPHR use and service delivery. Comparisons were made between invited and usual-care patients and between users and nonusers among those invited to use the IPHR. RESULTS: At 4 and 16 months, 229 (10.2%) and 378 (16.8%) of invited patients used the IPHR. The proportion of patients up-to-date with all services increased between baseline and 16 months by 3.8% among intervention patients (from 11.4% to 15.2%, P <.001) and by 1.5% among control patients (from 11.1% to 12.6%, P = .07), a difference of 2.3% (P = .05). Greater increases were observed among patients who used the IPHR. At 16 months, 25.1% of users were up-to-date with all services, double the rate among nonusers. At 4 months, delivery of colorectal, breast, and cervical cancer screening increased by 19%, 15%, and 13%, respectively, among users. CONCLUSIONS: Information systems that feature patient-centered functionality, such as the IPHR, have potential to increase preventive service delivery. Engaging more patients to use systems could have important public health benefits.

Health care reform 2011: opportunities for pharmacists.

The health reforms of the last several years at the federal and state levels have created many opportunities for pharmacists to become actively involved in the direct patient care provision. Indeed, the statutory language in some sections of the Affordable Care Act of 2010 creates expectations of pharmacists that will require practice transformation if we are to arise to accept the responsibilities associated with these expectations. These new opportunities open the door for pharmacists to benefit community-dwelling patients with chronic medical conditions, those with acute/emergent care needs, those experiencing a transition between chronic and acute care and vice versa, as well as others in long-term care settings. Although the profession has demonstrated value in many practice environments, our contributions to improved medication-related patient outcomes through medication therapy management (MTM) and the other pharmaceutical care services remain to be rigorously quantified. Incorporation of pharmacists either by their physical presence within the practice or through the design of effective community linkages, such as electronic health records, must be developed to meet the needs of rural and urban patients seen in a variety of practice settings. New business models that build upon cognitive and direct patient care services in addition to the provision of drug products will surely need to emerge for the profession to become a viable and vital component of the US health care system.

Executive summary: The Virginia Commonwealth University pharmacy practice transformation conference.

Pharmacy practice transformation was the focus of an invitational conference held in June 2011 to address the current status of the practice of pharmacy in Virginia and elucidate the consensus on future directions from pharmacists across the commonwealth. The series of presentations provided visionary perspectives on the role that pharmacists can have in the collaborative management of patients with chronic disease states, the optimal pharmacy practice model for direct patient care delivery in acute care settings, and payment for pharmacists' cognitive services, such as medication therapy management (MTM). The discussion groups were structured to have conference participants first identify future goals for pharmacy practice and then consider strategies to achieve these goals. The conference concluded with a consensus development dialogue that revealed the priorities as well as the strategies that needed to be employed to move the profession toward its goals.

Pharmacy practice in Virginia in 2011.

BACKGROUND: Opportunities for pharmacy practice reform exist at state and national levels. The Virginia Commonwealth University (VCU) School of Pharmacy created a working group to assess these opportunities with a mission to advance pharmacy practice in Virginia. OBJECTIVES: To assess the perceptions of chronic and acute care pharmacy practice and confidence in providing patient care and medication therapy management (MTM) activities and characterize current work activities of pharmacists in Virginia. METHODS: A cross-sectional, online survey was used. VCU School of Pharmacy pharmacist preceptors, students, and faculty members were eligible. The questionnaire contained items that assessed perceptions of chronic and acute care pharmacy practice and confidence in patient care and MTM activities. Demographic and practice site characteristics were also collected. RESULTS: A total of 974 preceptors, 515 students, and 78 faculty members were invited to participate, and 335 preceptors, 155 students, and 41 faculty members had usable responses, yielding response rates of 34%, 30%, and 53%, respectively. Preceptors, students, and faculty members favorably viewed direct patient care roles in the chronic and acute care settings. Pharmacists were very confident or confident in performing many patient care and MTM activities. They were least confident in considering genetic characteristics when adjusting medications and creating business plans for new services. Many pharmacists in chronic and acute care settings provided some type of patient care service, but few were regularly providing services. Inadequate time, staffing, and reimbursement, and lack of perceived value from patients and providers were most frequently cited as barriers to service provision. CONCLUSIONS: VCU preceptors, students, and faculty members overwhelmingly believe that pharmacists should provide direct patient care and MTM activities. To transform pharmacy practice, it will be important to define the pharmacist's role, responsibilities, and expected outcomes and to consider time, staffing, and compensation as well as to engage patients and providers.

Drug dosing consideration in patients with acute and chronic kidney disease-a clinical update from Kidney Disease: Improving Global Outcomes (KDIGO).

Drug dosage adjustment for patients with acute or chronic kidney disease is an accepted standard of practice. The challenge is how to accurately estimate a patient's kidney function in both acute and chronic kidney disease and determine the influence of renal replacement therapies on drug disposition. Kidney Disease: Improving Global Outcomes (KDIGO) held a conference to investigate these issues and propose recommendations for practitioners, researchers, and those involved in the drug development and regulatory arenas. The conference attendees discussed the major challenges facing drug dosage adjustment for patients with kidney disease. In particular, although glomerular filtration rate is the metric used to guide dose adjustment, kidney disease does affect nonrenal clearances, and this is not adequately considered in most pharmacokinetic studies. There are also inadequate studies in patients receiving all forms of renal replacement therapy and in the pediatric population. The conference generated 37 recommendations for clinical practice, 32 recommendations for future research directions, and 24 recommendations for regulatory agencies (US Food and Drug Administration and European Medicines Agency) to enhance the quality of pharmacokinetic and pharmacodynamic information available to clinicians. The KDIGO Conference highlighted the gaps and focused on crafting paths to the future that will stimulate research and improve the global outcomes of patients with acute and chronic kidney disease.

Influence of continuous venovenous hemofiltration and continuous venovenous hemodiafiltration on the disposition of doripenem.

The pharmacokinetics, safety, and tolerability of a single 1-hour, 500-mg intravenous infusion of doripenem were assessed in dialysis-dependent subjects with stage 5 chronic kidney disease undergoing continuous renal replacement therapy (CRRT) via 12-hour continuous venovenous hemofiltration (CVVH) (n = 6) or continuous venovenous hemodiafiltration (CVVHDF) (n = 5). Healthy volunteers were also assessed (n = 12). Concentrations of doripenem and the primary metabolite doripenem-M-1 were measured in plasma and ultrafiltrate or ultrafiltrate/dialysate by a validated liquid chromatography-tandem mass spectrometry method. In dialysis-dependent subjects, levels of systemic exposure to doripenem and doripenem-M-1 were approximately 3- and 5-fold greater, respectively, than those in healthy subjects: for doripenem, 98 µg·h/ml for CVVH and 77 µg·h/ml for CVVHDF versus 32 µg·h/ml for healthy subjects, and for doripenem-M-1, 24 µg·h/ml for CVVH and 22 µg·h/ml for CVVHDF versus 4.7 µg·h/ml for healthy subjects. The mean sieving coefficients and saturation coefficients were >0.67 for both doripenem and doripenem-M-1. During CVVH and CVVHDF, respectively, the percentages of administered doripenem dose removed were 38% and 29%, and clearances of doripenem were 22 and 25 ml/min. Both CVVH and CVVHDF efficiently removed doripenem and doripenem-M-1. Despite significant removal of drug by CVVH and CVVHDF, a single 1-hour, 500-mg doripenem infusion produced significantly higher plasma concentrations of doripenem, higher systemic exposure (area under the plasma concentration-time curve from time zero to 12 h after the start of infusion [AUC(0-12)]), and longer half-life (t(1/2)) in subjects receiving CVVH or CVVHDF than in healthy volunteers. The recovery of drug in ultrafiltrate and ultrafiltrate/dialysate and the enhanced rate of reduction of plasma concentrations indicate that CVVH and CVVHDF significantly augmented residual total body clearance of doripenem in subjects receiving CRRT. Doripenem dosage regimens for patients receiving CRRT thus need to be adjusted.

Health Care Policy 2011: implications for pharmacists.

OBJECTIVE: The enactment of the Patient Protection and Affordable Care Act of 2010 set the stage for a new era. The 2010 Congressional election results and recent court rulings challenging the constitutionality of various provisions of the Act suggest that implementation will be anything but straightforward. The proposed changes in health insurance, along with modifications in current reimbursement models, will alter the health-care environment. It is important for pharmacists to be aware of these opportunities and the resultant changes in public expectations. It is with these considerations in mind that The Annals announces the creation of a Health Care Policy expert panel to initiate commentary and discussion regarding health-care policy issues of relevance to the pharmacy community.

Integration of collaborative medication therapy management in a safety net patient-centered medical home.

OBJECTIVE: To describe the integration of collaborative medication therapy management (CMTM) into a safety net patient-centered medical home (PCMH). SETTING: Federally qualified Health Care for the Homeless clinic in Richmond, VA, from October 2008 to June 2010. PRACTICE DESCRIPTION: A CMTM model was developed by pharmacists, physicians, nurse practitioners, and social workers and integrated with a PCMH. CMTM, as delivered, consisted of (1) medication assessment, (2) development of care plan, and (3) follow-up. PRACTICE INNOVATION: CMTM is integrated with the medical and mental health clinics of PCMH in a safety net setting that serves homeless individuals. MAIN OUTCOME MEASURES: Number of patients having a CMTM encounter, number and type of medication-related problems identified for a subset of patients in the mental health and medical clinics, pharmacist recommendations, and acceptance rate of pharmacist recommendations. RESULTS: Since October 2008, 695 patients have had a CMTM encounter. An analysis of 209 patients in the mental health clinic indicated that 425 medication-related problems were identified (2.0/patient). Pharmacists made 452 recommendations to resolve problems, and 384 (85%) pharmacist recommendations were accepted by providers and/or patients. For 40 patients in the medical clinic, 205 medication-related problems were identified (5.1/patient). Pharmacists made 217 recommendations to resolve the problems, and 194 (89%) recommendations were accepted. CONCLUSION: Integrating CMTM with a safety net PCMH was a valuable patient-centered strategy for addressing medication-related problems among homeless individuals. The high acceptance rate of pharmacist recommendations demonstrates the successful integration of pharmacist services.

Health-care reform 2010: how will it impact you and your practice?

There are several transformative features of the 2 landmark health-care reform laws passed by the Congress and signed into law by the President in March. The most critical elements that will impact pharmacists and patients are categorized into 6 key areas in this commentary: health insurance reform; improvements in Medicare and Medicaid; pharmacy practice expansion; health professions education and workforce initiatives; prevention and wellness; and enhanced access to affordable medications. The relevant features of these new opportunities are presented and the implications for pharmacists and their patients are discussed.

Healthcare reform 2009 and its implications for pharmacists.

The US healthcare system has been widely criticized by many and praised by others for many reasons that are not mutually exclusive. There is no doubt that, compared with our peer industrialized countries, the US ranks near the bottom in many of the benchmark criteria such as life expectancy, infant mortality, and mortality of the population that is amenable to health care. Despite these shortcomings, the US has been a major innovator in healthcare technology including the development of biological and pharmacological drugs. The shortcomings of our system are often focused on the fact that a significant portion of the population lacks access to these cutting-edge resources and therapies. In this commentary, the healthcare reform proposals that have been introduced in 2008-2009, with a focus on the 3 leading plans that have been put forward by the House of Representatives and Senate, are reviewed. The inclusion of pharmacist-delivered medication therapy management (MTM) as well as medication reconciliation (MedRec) is specifically stated in 2 of the 3 plans. Integrated care delivery models (ie, community health teams, or "medical homes") are also directed to provide MedRec and MTM during transitions of care. Finally, in the Senate Health, Education, Labor, and Pensions language, there is a directive that health insurers implement a payment schedule for MTM and care compliance. The many other ways in which each of these evolving reform proposals may impact pharmacists and the care they deliver to their communities are also highlighted.

Comprehensive health management pharmacist-delivered model: impact on healthcare utilization and costs.

OBJECTIVES: To (1) examine the impact of the Comprehensive Health Management Patient Service (CHaMPS) on unplanned hospital admissions and emergency department (ED) visits in patients with chronic conditions, (2) describe the number and type of pharmacist interventions, and (3) determine the cost savings of CHaMPS. STUDY DESIGN: Retrospective, cross-sectional design with a matched comparator group. METHODS: CHaMPS integrated pharmacists within family medicine clinics to optimize medication use among patients with chronic conditions. Outcomes were the change in unplanned hospital admissions and ED visits from baseline to 180- and 365-day postintervention periods between the CHaMPS and propensity-matched comparator groups. Descriptive, bivariate (t tests and McNemar tests), and multivariate (general linear models) statistical analyses were used. Pharmacist interventions are reported and a cost-benefit analysis was conducted. RESULTS: A total of 624 patients (312 in the CHaMPS group and 312 in the comparator group) were included. Unplanned hospital admissions decreased in the CHaMPS group and increased in the comparator group (not significant). ED visits remained stable in the CHaMPS group but increased significantly in the comparator group, resulting in a significant mean change in ED visits between the groups at the 180- and 365-day postintervention periods (P = .03 for both periods). Pharmacists provided a total of 5705 medication-related problem, education, and medication reconciliation interventions (18.3 per patient). The benefit-cost ratio ranged from 2.1:1 to 2.6:1. CONCLUSIONS: CHaMPS achieved its goals by demonstrating a positive impact on ED visits and a benefit-cost ratio greater than 1.0. The cost savings of the embedded pharmacist model are most beneficial from a payer perspective or an accountable care organization approach to healthcare.

An in vivo-in vitro study of cefepime and cefazolin dialytic clearance during high-flux hemodialysis.

STUDY OBJECTIVES: To assess the influence of in vitro and in vivo hemodialysis with a new high-flux dialyzer on the clearance of cefazolin and cefepime; to assess the correlation of in vivo dialytic clearance of these antibiotics with blood flow rate; and to assess the correlation between in vitro and in vivo dialytic clearances of these antibiotics. DESIGN: Prospective, open-label, dialysis clearance study. SETTING: A tertiary-care, university health science center. PATIENTS: Five adults who received high-flux hemodialysis 3 times/week. Intervention. For the in vivo experiment, patients received a single intravenous infusion of cefazolin 1 g and cefepime 1 g before dialysis and then underwent a modified hemodialysis session. For the in vitro experiment, a buffered simulated plasma water (SPW) solution containing cefazolin and cefepime was used. Hemodialysis for both experiments was performed with use of a new high-flux polysulfone dialyzer. MEASUREMENTS AND MAIN RESULTS: Cefazolin and cefepime dialytic clearances were determined at blood and/or SPW flow rates of 100, 200, 300, and 400 ml/minute after a 15-minute equilibration period. The degree of correlation of in vitro and in vivo clearances with blood flow rate was determined. Cefepime dialytic clearance increased proportionally with blood flow rate (p<0.01), reaching a maximum mean +/- SD value of 178.9 +/- 24.3 ml/minute at a blood flow rate of 400 ml/minute. Cefazolin dialytic clearance ranged from a mean +/- SD of 42.3 +/- 7.7 to 52.7 +/- 16 ml/minute; no significant correlation was noted between blood flow rate and dialytic clearance. In vitro cefazolin and cefepime dialytic clearances increased proportionally with SPW flow rate (p<0.05). After adjusting the in vitro cefazolin and cefepime dialytic clearances based on their degrees of protein binding, the correlation between the in vitro and in vivo cefepime dialytic clearances was significant (r(2)=0.91, p=0.04), but no significant correlation was noted between the in vitro and in vivo cefazolin clearances (r(2)=0.61, p=0.22). CONCLUSION: The in vivo hemodialysis clearances of cefepime and cefazolin with the new high-flux polysulfone dialyzer used in this study are markedly higher than values reported with conventional dialyzers but similar to values observed with other high-flux hemodialyzers. The in vivo dialytic clearance of cefazolin was significantly lower than the in vitro values, most likely due to cefazolin's high degree of protein binding. These results highlight the limitation of directly applying in vitro data to clinical situations.

Impact of a pharmacist-physician collaborative care model on patient outcomes and health services utilization.

PURPOSE: The impact of a pharmacist-physician collaborative care model on patient outcomes and health services utilization is described. METHODS: Six hospitals from the Carilion Clinic health system in southwest Virginia, along with 22 patient-centered medical home (PCMH) practices affiliated with Carilion Clinic, participated in this project. Eligibility criteria included documented diagnosis of 2 or more of the 7 targeted chronic conditions (congestive heart failure, hypertension, hyperlipidemia, diabetes mellitus, asthma, chronic obstructive pulmonary disease, and depression), prescriptions for 4 or more medications, and having a primary care physician in the Carilion Clinic health system. A total of 2,480 evaluable patients were included in both the collaborative care group and the usual care group. The primary clinical outcomes measured were the absolute change in values associated with diabetes mellitus, hypertension, and hyperlipidemia management from baseline within and between the collaborative care and usual care groups. RESULTS: Significant improvements (p < 0.01) in glycosylated hemoglobin, blood pressure, low-density-lipoprotein cholesterol, and total cholesterol were observed in the collaborative care group compared with the usual care group. Hospitalizations declined significantly in the collaborative care group (23.4%), yielding an estimated cost savings of $2,619 per patient. The return on investment (net savings divided by program cost) was 504%. CONCLUSION: Inclusion of clinical pharmacists in this physician-pharmacist collaborative care-based PCMH model was associated with significant improvements in patients' medication-related clinical health outcomes and a reduction in hospitalizations.

Population health and medicine: Policy and financial drivers.

PURPOSE: The financial and policy levers of population health and potential opportunities for pharmacists are described. SUMMARY: Three long-standing problems drive the focus on population health: (1) the United States suffers far worse population health outcomes compared with those of other developed nations that spend significantly less on healthcare, (2) the U.S. healthcare system's focus on "sick care" fails to address upstream prevention and population health improvement, and (3) financial incentives for healthcare delivery are poorly aligned with improvements in population health outcomes. The Patient Protection and Affordable Care Act of 2010 (ACA) was arguably the first major healthcare legislation since 1965 and had 3 main strategies for improving population health: expand health insurance coverage, control healthcare costs, and improve the healthcare delivery system. Federal and state legislation as well as Medicare and Medicaid financing strategies have designated mechanisms to reward advances in population outcomes since the passage of the ACA. States are responsible for many of the factors that affect population health, and a bipartisan effort that builds upon state and federal collaboration will likely be needed to implement the necessary health policy initiative. Population health issues affect productivity in the United States; conversely, improvements in population health may increase productivity, helping to offset the rising federal debt. Employers are in a position to improve population health and consequently help reduce the federal debt by addressing lifestyle, chronic disease, poverty, and inequality. National pharmacy organizations, regulatory bodies, and journal editors need to collectively agree to a threshold of quality and rigor for publication and endorsement. CONCLUSION: Knowledge of the policy and financial drivers of population health may both support pharmacists' efforts to improve population outcomes and identify opportunities for professional advancement.

Liver disease selectively modulates cytochrome P450--mediated metabolism.

BACKGROUND: The liver plays a significant role in drug metabolism; thus it would be expected that liver disease may have a detrimental effect on the activity of cytochrome P450 (CYP) enzymes. The extent to which the presence and severity of liver disease affect the activity of different individual drug-metabolizing enzymes is still not well characterized. The purpose of this study was to assess the effect of liver disease on multiple CYP enzymes by use of a validated cocktail approach. METHODS: The participants in this investigation were 20 patients with different etiologies and severity of liver disease and 20 age-, sex-, and weight-matched healthy volunteers. Liver disease severity was categorized by use of the Child-Pugh score. All participants received a cocktail of 4 oral drugs simultaneously, caffeine, mephenytoin, debrisoquin (INN, debrisoquine), and chlorzoxazone, as in vivo probes of the drug-metabolizing enzymes CYP1A2, CYP2C19, CYP2D6, and CYP2E1, respectively. The primary end points were measurements of specific CYP metabolism indexes for each enzyme. RESULTS: Mephenytoin metabolism was significantly decreased in both patients with mild liver disease (Child-Pugh score of 5/6) (-63% [95% confidence interval (CI), -86% to -40%]; P = .0003) and patients with moderate to severe liver disease (Child-Pugh score >6) (-80% [95% CI, -95% to -64%]; P = .0003). In comparison with control subjects, the caffeine metabolic ratio was 69% lower (95% CI, -85% to -54%; median, 0.14 versus 0.62; P = .0003), the debrisoquin recovery ratio was 71% lower (95% CI, -96% to -47%; median, 0.10 versus 0.65; P = .012), and the chlorzoxazone metabolic ratio was 60% lower (95% CI, -91% to -29%; median, 0.21 versus 0.83; P = .0111) in patients with moderate to severe liver disease. All 4 drugs showed significant negative relationships with the Child-Pugh score. CONCLUSIONS: CYP enzyme activity is differentially affected by the presence of liver disease. We propose that the data can be explained by the "sequential progressive model of hepatic dysfunction," whereby liver disease severity has a differential effect on the metabolic activity of specific CYP enzymes.

Effect of conjugated equine estrogens on oxidative metabolism in middle-aged and elderly postmenopausal women.

The effects of conjugated equine estrogens (CEE) 0.625 mg daily on cytochrome P450 (CYP) were quantified in 12 middle-aged and 13 elderly postmenopausal women at baseline and 6 months later. CYP phenotype was characterized by caffeine (CYP1A2), chlorzoxazone (CYP2E1), dapsone (CYP, N-acetyltransferase 2), dextromethorphan (CYP2D6), and mephenytoin (CYP2C19) metabolism. CEE significantly decreased CYP1A2 (caffeine metabolic ratio: 0.57 +/- 0.20 before, 0.40 +/- 0.20 after, P = .001) and significantly increased CYP2D6 (dextromethorphan/dextrorphan ratio: 0.0116 +/- 0.0143 before, 0.0084 +/- 0.0135 after, P = .022) metabolism. CEE had no overall effect on CYP2C19, CYP2E1, CYP-mediated dapsone metabolism, and N-acetyltransferase 2. The dextromethorphan metabolic ratio decreased only in the seniors. The dapsone recovery ratio decreased in the middle-aged group and increased in the seniors. CEE significantly influenced CYP1A2, CYP2D6, and CYP-mediated dapsone oxidative metabolism but not CYP2C19, CYP2E1, or N-acetyltransferase 2 metabolism in postmenopausal women. Age influenced CYP2D6 metabolism and dapsone hydroxylation.

Influence of kidney disease on drug disposition: An assessment of industry studies submitted to the FDA for new chemical entities 1999-2010.

In 1998, the United States Food and Drug Administration (FDA) released the first guidance for industry regarding pharmacokinetic (PK) studies in renally impaired patients. This study aimed to determine if the FDA renal PK guidance influenced the frequency and rigor of renal studies conducted for new chemical entities (NCEs). FDA-approved package inserts (APIs) and clinical pharmacology review documents were analyzed for 194 NCEs approved from 1999 to 2010. Renal studies were conducted in 71.6% of NCEs approved from 1999 to 2010, a significant increase over the 56.3% conducted from 1996 to 1997 (P = .0242). Renal studies were more likely to be completed in highly renally excreted drugs (fe ≥ 30%) compared with drugs with low renal excretion, fe < 30% (89.6% vs 65.8%, P = .0015). PK studies to assess the impact of dialysis were conducted for 31.7% of NCEs that had a renal study: a greater proportion of high fe NCEs were studied (44.2% vs 26.0%, P = .0335). No significant change in frequency or rigor of PK studies was detected over time. The majority of NCEs (76.3%) with a renal study provided specific dosing recommendations in the API. The adoption of the 1998 FDA guidance has resulted in improved availability of PK and drug-dosing recommendations, particularly for high fe drugs.

Improving Health of At-Risk Rural Patients project: A collaborative care model.

PURPOSE: The design elements of the Improving Health of At-Risk Rural Patients (IHARP) care model are described. SUMMARY: The IHARP project evaluated the clinical, economic, and humanistic outcomes associated with the collaborative care model relative to usual care in the community. The care model was initiated in 22 level 3- certified patient-centered medical homes. The primary outcomes are the absolute change in all relevant clinical and laboratory values of patients with hypertension, hyperlipidemia, and diabetes within and between the intervention and comparator groups; the change in the absolute number of emergency department visits and hospitalizations; and the change in the cost of care among the Medicare and Medicaid intervention patients. The lessons learned during the implementation and conduction of this project over the past three years are also presented. Patient enrollment ended in December 2014, final patient care visits were concluded in the fall of 2015, and results are expected in late 2016 or early 2017. CONCLUSION: This project will provide information from patients, physicians, and midlevel providers regarding their perceptions of clinical pharmacists as collaborative care team members. Data on health outcomes, health services utilization, and costs of care drawn from over 1600 Medicare beneficiaries will provide a robust assessment of the value of the IHARP care delivery model.