Differences in quality of anticoagulation care delivery according to ethnoracial group in the United States: A scoping review.

Anticoagulation therapy is standard for conditions like atrial fibrillation, venous thromboembolism, and valvular heart disease, yet it is unclear if there are ethnoracial disparities in its quality and delivery in the United States. For this scoping review, electronic databases were searched for publications between January 1, 2011 - March 30, 2022. Eligible studies included all study designs, any setting within the United States, patients prescribed anticoagulation for any indication, outcomes reported for ≥ 2 distinct ethnoracial groups. The following four research questions were explored: Do ethnoracial differences exist in 1) access to guideline-based anticoagulation therapy, 2) quality of anticoagulation therapy management, 3) clinical outcomes related to anticoagulation care, 4) humanistic/educational outcomes related to anticoagulation therapy. A total of 5374 studies were screened, 570 studies received full-text review, and 96 studies were analyzed. The largest mapped focus was patients' access to guideline-based anticoagulation therapy (88/96 articles, 91.7%). Seventy-eight articles made statistical outcomes comparisons among ethnoracial groups. Across all four research questions, 79 articles demonstrated favorable outcomes for White patients compared to non-White patients, 38 articles showed no difference between White and non-White groups, and 8 favored non-White groups (the total exceeds the 78 articles with statistical outcomes as many articles reported multiple outcomes). Disparities disadvantaging non-White patients were most pronounced in access to guideline-based anticoagulation therapy (43/66 articles analyzed) and quality of anticoagulation management (19/21 articles analyzed). Although treatment guidelines do not differentiate anticoagulant therapy by ethnoracial group, this scoping review found consistently favorable outcomes for White patients over non-White patients in the domains of access to anticoagulation therapy for guideline-based indications and quality of anticoagulation therapy management. No differences among groups were noted in clinical outcomes, and very few studies assessed humanistic or educational outcomes.

Digital dashboards for direct oral anticoagulant surveillance, intervention and operational efficiency: uptake, obstacles, and opportunities.

Direct oral anticoagulants (DOAC) are the most widely prescribed oral anticoagulants in the United States. Despite advantages over warfarin, system-level improvements are needed to optimize outcomes. While Veterans Health Administration and others have described successful DOAC management dashboard implementation, the extent of use nationally is unknown. A survey of Anticoagulation Forum's members was conducted to assess access to digital tools available within a dashboard and to describe implementation models. An Expert Forum was subsequently convened to identify barriers to dashboard development and adoption. Responses were received from 340 targeted recipients (8.5% of invitees). Only a minority of inpatient (25/52, 48.1%) and outpatient (47/133, 35.3%) respondents outside of Veterans Health Administration were able to generate rosters of DOAC users on-demand, and fewer had the ability to digitally display key clinical data elements, identify drug-related problems, document interventions, or generate reports. The lack of regulatory requirements regarding Anticoagulation Stewardship was identified by the Expert Forum as the major barrier to widespread development of digital tools for improved anticoagulation management. While some health systems have demonstrated the feasibility of DOAC dashboards and described their impact on quality and efficiency, these tools do not appear to be widely available in the United States apart from Veterans Health Administration. The lack of regulatory requirements for Anticoagulation Stewardship may be the primary barrier to the development of digital resources to better manage anticoagulants. Efforts to secure regulatory requirements for Anticoagulation Stewardship are needed, and evidence of improvements in clinical and financial outcomes through DOAC dashboard use will likely bolster such efforts.

Digital dashboards for oral anticoagulation management: a literature scoping review.

This scoping review summarizes the extent and characteristics of the published literature describing digital population management dashboards implemented to improve the quality of anticoagulant management. A standardized search protocol was executed to identify relevant manuscripts published between January 1, 2015 and May 31, 2022. The resulting records were systematically evaluated by multiple blinded reviewers and the findings from selected papers were evaluated and summarized. Twelve manuscripts were identified, originating from 5 organizations within the US and 2 from other countries. The majority (75%) described implementation in the outpatient setting. The identified papers described a variety of positive results of dashboard use, including a 24.5% reduction of questionable direct oral anticoagulant dosing in one organization, a 33.3% relative improvement in no-show appointments in an ambulatory care clinic, and a 75% improvement in intervention efficiency. One medical center achieved a 98.4% risk-appropriate venous thromboembolism risk prophylaxis prescribing rate and 40.6% reduction in anticoagulation-related adverse event rates. The manuscripts primarily described retrospective findings from single-center dashboard implementation experiences. Digital dashboards have been successfully implemented to support the anticoagulation of acute and ambulatory patients and available manuscripts suggest a positive impact on care-related processes and relevant patient outcomes. Prospective studies are needed to better characterize the implementation and impact of dashboards for anticoagulation management. Published reports suggest that digital dashboards may improve the quality, safety, and efficiency of anticoagulation management. Additional research is needed to validate these findings and to understand how best to implement these tools.

Standardizing periprocedural anticoagulation management: a stewardship initiative.

BACKGROUND: Study data indicates anticoagulant interruption peri-procedurally can increase the risk of anticoagulation-related bleeding and thrombosis. Management of anticoagulated patients during the peri-procedural period poses clinical challenges given the potential for thrombosis and bleeding in this complex, high risk population. As such, there is a need for enhanced emphasis on anticoagulated patient care throughout the peri-procedural period with the goal of optimizing patient safety and efficacy. PURPOSE: To operationalize an effective, efficient, comprehensive, and standardized anticoagulation management peri-procedural process housed within the electronic health record (EHR). DESIGN: The IPRO-MAPPP clinical decision support logic was adapted into a nurse-managed protocol to guide anticoagulation therapy use during the elective peri-procedural period at Bassett Medical Center, an Anticoagulation Forum Center of Excellence. A second phase of this initiative endorsed peri-procedural warfarin and bridging management by the Anticoagulation Management Service. RESULTS: Outcomes revealed 30-day hospital or emergency department admissions remained at or below 1% of the surgical patient population, and below the published national standards for both phases of implementation. Further, no emergent anticoagulation reversal agent use was attributed to peri-procedural care during the assessment period. CONCLUSIONS: The phased implementation of this Anticoagulation Stewardship initiative in elective peri-procedural anticoagulation management successfully describes the operationalization and demonstration of high-quality care and low provider practice variation from policy. The integration of clinical decision support systems, in consort with effective communication, via the EHR, provides stability, sustainability, and drives high quality care to optimize patient outcomes.

Defining Minimum Necessary Communication During Care Transitions for Patients on Antihyperglycemic Medication: Consensus of the Care Transitions Task Force of the IPRO Hypoglycemia Coalition.

INTRODUCTION: Antihyperglycemic agents are significant contributors to adverse drug events, responsible for emergency department visits, hospitalizations, and death. Nationally, the rate of serious hypoglycemic events associated with these agents remains high despite widespread efforts to improve drug safety. Transitions of care between healthcare settings can lead to communication challenges between care professionals and increase the risk of adverse drug events. System-based improvements are needed to assure the safe transitions for patients with diabetes who are on antihyperglycemic agents. The objective of this study was to develop a consensus list of requisite elements that should be communicated between care settings during transitions of patients who are prescribed antihyperglycemic agents. METHODS: The Island Peer Review Organization (IPRO) Hypoglycemia Coalition identified suboptimal transitions of care as a barrier to improving patient safety and quality of diabetes care. The Coalition formed a multidisciplinary Task Force with experts in the field of diabetes care. The Task Force created a draft list of requisite communication elements through literature review and deliberation on monthly conference calls. A blinded iterative Delphi process was subsequently performed to generate a consensus list of requisite communication elements that participating experts agreed were necessary to safely and effectively assume the management of patients with diabetes upon care transitions. RESULTS: The Task Force completed a series of four iterative polls from September 2015 to August 2016, resulting in a final list of 22 requisite communication elements (the Diabetes Management Discharge Communication List), with the elements conceptually categorized into three domains: diagnosis and treatment, factors affecting glycemic control or patient risk, and patient self-management. CONCLUSIONS: The Diabetes Management Discharge Communication List provides an initial framework for the development of diabetes-specific resources to improve clinical communication between care settings.

Reversal of direct oral anticoagulants: Guidance from the Anticoagulation Forum.

Two specific reversal agents for direct oral anticoagulants (DOACs) have been approved in the United States: idarucizumab for dabigatran reversal and andexanet alfa for apixaban and rivaroxaban reversal. Non-specific prohemostatic agents such as prothrombin complex concentrate (PCC) and activated PCC have also been used for DOAC reversal. The goal of this document is to provide comprehensive guidance from the Anticoagulation Forum, a North American organization of anticoagulation providers, regarding use of DOAC reversal agents. We discuss indications for reversal, provide guidance on how the individual reversal agents should be administered, and offer suggestions for stewardship at the health system level.

Uptake and Utilization of the Management of Anticoagulation in the Periprocedural Period App: Longitudinal Analysis.

BACKGROUND: Anticoagulants are major contributors to preventable adverse drug events, and their optimal management in the periprocedural period is particularly challenging. Traditional methods of disseminating clinical guidelines and tools cannot keep pace with the rapid expansion of available therapeutic agents, approved indications for use, and published medical evidence, so a mobile app, Management of Anticoagulation in the Periprocedural Period (MAPPP), was developed and disseminated to provide clinicians with guidance that reflects the most current medical evidence. OBJECTIVE: The objective of this study was to assess the global, national, and state-level acquisition of a mobile app since its initial release and characterize individual episodes of use based on drug selection, procedural bleeding risk, and patient thromboembolic risk. METHODS: Data were extracted from a mobile app usage tracker (Google Analytics) to characterize new users and completed episodes temporally (by calendar quarter) and geographically (globally, nationally, and in the targeted US state of New York) for the period between April 1, 2016 and September 30, 2017. RESULTS: The app was acquired by 2866 new users in the measurement period, and the users completed nearly 10,000 individual episodes of use. Acquisition and utilization spanned 51 countries globally, predominantly in the United States and particularly in New York State. Warfarin and rivaroxaban were the most frequently selected drugs, and completed episodes most frequently included the selection of high bleeding risk (4888/9963, 49.06%) and high thromboembolic risk categories (4500/9963, 45.17%). CONCLUSIONS: The MAPPP app is a successful means of disseminating current guidance on periprocedural anticoagulant use, as indicated by broad global uptake and upward trends in utilization. Limitations in access to provider and patient-specific data preclude objective evaluation of the clinical impact of the app. An ongoing study incorporating app logic into electronic health record systems at participant health systems will provide a more definitive evaluation of the clinical impact of the app logic.

Defining Minimum Necessary Anticoagulation-Related Communication at Discharge: Consensus of the Care Transitions Task Force of the New York State Anticoagulation Coalition.

BACKGROUND: Anticoagulated patients are particularly vulnerable to ADEs when they experience changes in medical acuity, pharmacotherapy, or care setting, and resources guiding care transitions are lacking. The New York State Anticoagulation Coalition convened a task force to develop a consensus list of requisite data elements (RDEs) that should accompany all anticoagulated patients undergoing care transitions. METHODS: A multidisciplinary panel of 15 anticoagulation experts voluntarily completed an iterative Delphi process. Resources were disseminated and deliberated via remote technology, with consensus achieved via blinded electronic polling. RESULTS: The panel reached consensus on a list of 15 RDEs for anticoagulation communication at discharge (the ACDC List). Consensus was rapidly achieved by the full panel on 13 elements, while 3 (2 of which were combined into 1 element) required multiple iterations and achieved consensus with votes from 8 available panelists. The elements encompassed a range of factors, including drug use and indications, previous exposure and duration of therapy, recent drug exposure and laboratory results and expectations for subsequent administration, therapy goals, patient education and comprehension, and expectations for clinical management. Twelve of the elements are applicable to any anticoagulant, and 3 are specific to warfarin. CONCLUSION: The ACDC List identifies specific pieces of clinical information that a panel of anticoagulant experts agree should be communicated to downstream providers for all anticoagulated patients undergoing care transitions. Additional study is needed to objectively evaluate the ability of existing care systems to communicate the elements and to assess possible relationships between communication of the elements and clinical outcomes.

Trends in Warfarin Monitoring Practices Among New York Medicare Beneficiaries, 2006-2011.

Anticoagulation with warfarin requires frequent evaluation of the international normalized ratio (INR), and less invasive testing devices are available for use by clinicians at the point-of-care (POC) and by patients who self-test (PST). Despite commercial availability and positive results of published studies, evidence suggests that adoption of less invasive (POC/PST) testing in the United States is slow. Considering the equivalence of results and logistical advantages of POC/PST testing, slow uptake may indicate a gap in quality of care warranting evaluation and possibly intervention. This study used Medicare fee for service claims data to explore the uptake of POC/PST INR monitoring across New York State over a 6 year time frame (2006-11), with additional analyses based on beneficiary age, sex, race and ethnicity and income by county. In 2006, only 28.3% of 103,410 analyzable beneficiaries presumed to be chronic warfarin users based on INR testing patterns were monitored by POC/PST, and increased to only 37.6% by 2011. Utilization of POC/PST testing varied widely by county (baseline range 1.2-89.4%), and uptake of these testing modalities in New York State was significantly lower among the very elderly, women, and ethnic minorities. We hypothesize that poor penetration of these less invasive INR testing modalities into highly populated New York City and barriers to POC utilization in long term care facilities may account for a portion of the variability in INR testing patterns observed in this study. However, additional research is needed to further explore whether disparities in warfarin monitoring practices exist.

Features of electronic health records necessary for the delivery of optimized anticoagulant therapy: consensus of the EHR Task Force of the New York State Anticoagulation Coalition.

BACKGROUND: Oral anticoagulants are prescribed to millions of Americans, and consequently are among the medications most likely to contribute to emergency department visits and hospitalizations. Although guidelines and consensus statements promote systematic approaches to therapy, anticoagulation (AC) management is often suboptimal. Electronic health records (EHRs) have the potential to improve safety and quality but have not yet incorporated specialized features necessary to optimize therapy. OBJECTIVE: To generate a comprehensive, consensus-based list of EHR features clinically necessary to deliver optimized AC management, provide a "language bridge" to accelerate incorporation of features into EHR systems, and suggest mechanisms for the objective evaluation of available EHRs. METHODS: A multidisciplinary panel of AC specialists utilized the framework of a previously published consensus statement to map outpatient AC management and developed a comprehensive array of sequential computer logic steps using a restricted language scheme. Logic steps were then translated into narrative descriptions of potential EHR features, which were refined through multiple group evaluations. A finalized list of proposed features was ranked according to perceived clinical necessity by physician, pharmacist, and nurse panelists in a blinded manner using a 5-point Likert scale. Features receiving no more than 1 dissenting opinion were included in a finalized list of clinically necessary features. RESULTS: The task force generated 78 recommended EHR features across 20 key discrete areas and 425 individual logic steps. All recommended features received Strongly Agree or Agree rankings regarding their perceived clinical necessity, and no feature received more than a single Disagree response. CONCLUSION: The incorporation of key AC-related features into existing EHRs or specialized AC management systems has the potential to systematize the delivery of optimal AC care by health care professionals at the point of care. Optimized AC management has the potential to reduce adverse drug events associated with anticoagulant therapy in the outpatient setting.

Improving warfarin safety in long-term care.

OBJECTIVE: To assess the impact of a multidisciplinary warfarin safety intervention on objective quality measurements. DESIGN: A pre-post comparison of aggregate performance following 12 months of intervention activities. SETTING: Long-term care facilities. PATIENTS, PARTICIPANTS: Twelve long-term care facilities in New York state. INTERVENTIONS: Interventions included serial data reports, pharmacy alerts, quality improvement meetings, and Webinars. MAIN OUTCOME MEASURES: The primary outcome was the proportion of residents receiving anticoagulation therapy and who were receiving timely International Normalized Ratio (INR) testing following initiation of an interacting antibiotic. Secondary outcomes included: time in therapeutic range (TTR), mean INR, mean time between INRs, proportion of INR values between 2.3 and 2.7, and the frequency of INR "excursions." RESULTS: Baseline analysis of the three-month preintervention period identified 207 warfarin-antibiotic coprescribing events, with only 70% being followed by a timely INR test. The baseline TTR was 45.49%, and the mean INR was 2.32. Baseline evaluations of facility policies and procedures identified process gaps in dosing and monitoring of warfarin. Intervention significantly improved the timeliness of INR monitoring (79.6%; P=0.03), but secondary measures were not measurably improved. Facility adherence to intervention implementation was poor, diminishing study impact. CONCLUSION: Anticoagulation management was suboptimal at baseline, and improvements were not seen despite repeated attempts to implement a structured, sequential intervention. Long-term care facilities may be unwilling or unable to voluntarily implement known best practices for anticoagulation management, suggesting that changes to regulations and reimbursement systems may be warranted.

Overactive bladder drugs and constipation: a meta-analysis of randomized, placebo-controlled trials.

BACKGROUND: Anticholinergic drugs are commonly prescribed for symptomatic treatment of overactive bladder (OAB). While recent meta-analyses have characterized the prevalence of dry mouth among patients utilizing OAB medications, prevalence of constipation has not been systematically reviewed. AIMS: To provide an effect measure for constipation associated with anticholinergic OAB drugs versus placebo. METHODS: A meta-analysis of trials with darifenacin, fesoterodine, oxybutynin, solifenacin, tolterodine, and trospium was conducted. All randomized, placebo-controlled studies of anticholinergic OAB drugs published in English language and identified in Medline and Cochrane databases were considered for inclusion in this meta-analysis. Those meeting predetermined design characteristics and having sufficient duration (≥2 weeks) were included. Constipation-related data from all included studies were abstracted. RESULTS: One hundred two English-language, randomized, placebo-controlled trials were originally identified. Thirty-seven studies were ultimately included in the analysis, involving 19,434 total subjects (12,368 treatment+7,066 placebo patients). The odds ratios for constipation compared with placebo were as follows: overall [odds ratio (OR) 2.18, 95% confidence interval (CI)=1.82-2.60], tolterodine (OR 1.36, 95% CI=1.01-1.85), darifenacin (OR 1.93, 95% CI=1.40-2.66), fesoterodine (OR 2.07, 95% CI=1.28-3.35), oxybutynin (OR 2.34, 95% CI=1.31-4.16), trospium (OR 2.93, 95% CI=2.00-4.28), and solifenacin (OR 3.02, 95% CI=2.37-3.84). CONCLUSIONS: Our results demonstrate that patients prescribed anticholinergic OAB drugs are significantly more likely to experience constipation. Differences in muscarinic receptor affinities among individual agents may possibly account for the modest variation in constipation rates observed; however, such a determination warrants additional research.

Deeply discounted medications: Implications of generic prescription drug wars.

OBJECTIVE: To describe the history of generic prescription pricing programs at major pharmacy chains and their potential implications on prescribing, quality of care, and patient safety. DATA SOURCES: Publicly available generic prescription discount program drug lists as of May 1, 2009. SUMMARY: Fierce competition among major pharmacy chains such as Walgreens, CVS, and Walmart has led to a generic prescription pricing war with unclear public health implications. Introduced in 2006, currently 7 of the 10 largest pharmacy chains advertise a version of a deeply discounted medication (DDM) program, accounting for more than 25,000 locations nationally. By early 2008, almost 70 million Americans had used these programs. Although DDM programs lower drug costs for many patients, DDM formularies include potentially ineffective or harmful medications, have the potential to influence physician prescribing behavior, and may impair pharmacists' ability to review complete drug-dispensing records. CONCLUSION: DDMs are widespread but have the potential for unintended consequences on patients, providers, and the health care system. A systematic review of DDMs needs to evaluate the clinical, economic, and system-level implications of such programs.

Assessing anticoagulation knowledge in patients new to warfarin therapy.

BACKGROUND: Warfarin is highly efficacious for the treatment and prevention of thromboembolic disorders. However, anticoagulation control has been a long-standing challenge, as patients' lack of knowledge of warfarin therapy is a predictor of nonadherence and compromised patient safety. OBJECTIVE: To ascertain whether hospitalized patients newly initiated on warfarin are provided adequate anticoagulation education during hospitalization, as measured at discharge, as well as determine whether there is a difference in the knowledge obtained by patients educated via a structured program versus those counseled by "usual care." METHODS: A prospective evaluation of warfarin education of inpatients new to warfarin therapy was performed at Bassett Medical Center, Cooperstown, NY. Patients who were admitted to the hospital and receiving warfarin for any given diagnosis, were >18 years of age and able to give informed consent, and spoke English were recruited. Patients with dementia or cognitive impairment, those who were pregnant, or those who had previously been on warfarin therapy were excluded. Recruited patients received warfarin education in the form of a structured program provided by a pharmacist or counseling by usual care during hospitalization. Prior to discharge, the Oral Anticoagulation Knowledge (OAK) test, a prevalidated tool used to measure warfarin knowledge, was administered to evaluate outcomes. Further warfarin education was provided posttest if necessary. RESULTS: The intervention group (n = 20) scored significantly higher on the OAK test than the usual care group (n = 20): 74% versus 55%, respectively (p = 0.004). CONCLUSIONS: This preliminary study demonstrated that there is a large amount of variability regarding patient knowledge of warfarin on discharge from an inpatient facility. A formalized inpatient warfarin education program may empower patients to achieve a larger degree of initial warfarin knowledge than those educated by usual care. Previous studies have demonstrated that this may improve adherence and subsequently increase long-term safety associated with oral anticoagulation. Larger, prospective, randomized studies are necessary to further evaluate patient education and safety outcomes.

First renin inhibitor, aliskiren, for the treatment of hypertension.

AIM OF THE REVIEW: To systematically analyze the efficacy and safety of aliskiren for the treatment of hypertension in comparison to placebo, other monotherapy, and various combination therapies. METHOD: A PubMed database (1966-June 2008) search was conducted with aliskiren as a search term with limits of humans, written in English, and in title only. Phase III pivotal clinical studies retrieved by PubMed database and resources such as printed labeling, approval letter, pharmacology reviews, and medical reviews posted in Drug@FDA website were evaluated with regard to study design and outcomes of efficacy and safety. RESULTS: Six Phase III pivotal clinical studies compared various doses of aliskiren to placebo and some studies compared aliskiren to treatment with other monotherapies or combinations. Aliskiren in doses of 300 mg showed a statistically significant reduction in both systolic and diastolic blood pressure versus placebo. Comparison to other antihypertensive treatments suggest that aliskiren doses of 150 and 300 mg may induce blood pressure changes similar to those seen with moderate doses of hydrochlorothiazide or angiotensin receptor blockers. Aliskiren in combination with angiotensin receptor blockers or hydrochlorothiazide showed additional blood pressure reduction only when higher doses of aliskiren were used. Aliskiren appears to be well tolerated, with diarrhea being the only statistically significant adverse event. CONCLUSION: Aliskiren is a novel antihypertensive that exerts its effects through the direct inhibition of renin. Although the drug is well tolerated, its modest effects on blood pressure and the present lack of evidence of impact on objective cardiovascular outcomes appear to limit its utility in the general treatment of hypertension at this time.

Effect of pharmaceutical care services on outcomes for home care patients with heart failure.

PURPOSE: The effect of pharmaceutical care services for home care patients with heart failure on death and rehospitalization rates was studied. METHODS: Eligible patients had to be at least 21 years old and included those with a primary or secondary diagnosis of heart failure who were referred to receive skilled nursing services. Patients were then randomized to receive usual care or pharmaceutical care. Patients assigned to the usual care group received the services typically provided by the visiting nurses association, while patients in the pharmaceutical care group received usual care plus standardized services from a clinical pharmacist. Pharmaceutical care services consisted of an initial comprehensive in home medication assessment and two follow-up visits. Throughout the three-week intervention period, the clinical pharmacist accessed and reviewed all pertinent physician notes and laboratory test values and interacted with prescribers on behalf of the patients as necessary. RESULTS: A total of 154 patients met all criteria and participated in the study. The pharmacist made 79 specific therapy recommendations, 47 (60%) of which were related directly to drug therapy for heart failure or cardiovascular disease. Overall, 14 therapy recommendations were fully implemented, and 10 heart failure-specific recommendations were fully implemented. Patients for whom the pharmacist had made recommendations that were followed by the prescriber had a reduced rate of the composite primary endpoint, but this difference did not reach statistical significance. CONCLUSION: A home-based pharmaceutical care model for recently hospitalized patients with heart failure did not significantly improve the combined rate of death or rehospitalization.

Exenatide: a new option for the treatment of type 2 diabetes.

OBJECTIVE: To evaluate available literature characterizing the pharmacology, pharmacokinetics, drug interactions, efficacy, and safety of exenatide in patients with type 2 diabetes. DATA SOURCES: A PubMed database search (1966-May 2006) was conducted, using exenatide as the search term. The manufacturer's prescribing information was also used. STUDY SELECTION AND DATA EXTRACTION: English-language articles were selected and data were extracted with a focus on clinical outcomes associated with the treatment of patients with type 2 diabetes. DATA SYNTHESIS: Exenatide exerts a glucoregulatory effect by various mechanisms including secretion of glucose-dependent insulin, suppression of inappropriately high glucagon levels in patients with type 2 diabetes, delayed gastric emptying, and reduction of food intake. In placebo-controlled clinical studies, plasma exenatide concentrations appeared to exhibit dose-proportional kinetics, reaching peak plasma levels between 2 and 3 hours after a single subcutaneous injection. Exenatide's elimination half-life ranged from 3.3 to 4.0 hours, and the time to reach maximum concentration was about 2 hours. Interactions between exenatide and agents such as digoxin and lisinopril were not considered significant. In Phase III trials, exenatide demonstrated significant reduction of hemoglobin A1c levels from baseline and compared with placebo after 30 weeks of treatment in patients unable to achieve optimal glycemic control with metformin, a sulfonylurea, or oral combination therapy (0.4-0.9%). Patients' weight decreased with exenatide (0.9-2.8 kg), but adverse gastrointestinal (GI) events were common. Exenatide combined with thiazolidonediones, D-phenylalanine derivatives, meglitinides, or alpha glucosidase inhibitors has not been studied. CONCLUSIONS: Clinical trials have demonstrated that exenatide improves glycemic control when added to sulfonylureas and metformin, and it may be an alternative to insulin glargine in patients requiring additional therapy. Hypoglycemia has been encountered in clinical trials of exenatide, especially upon initiation of therapy with sulfonylureas (not with metformin); close patient monitoring is therefore recommended. Further studies should assess the impact of exenatide on clinical outcomes such as micro- and macrovascular disease.

Recurrent acute nitrofurantoin-induced pulmonary toxicity.

Nitrofurantoin may be used for prophylaxis of recurrent urinary tract infections in women; however, this agent has been associated with acute, subacute, and chronic pulmonary adverse reactions. The acute reaction occurs in about 1/5,000 women after their first exposure to the drug. We report the occurrence of two successive, highly probable (by Naranjo score) nitrofurantoin-induced acute pulmonary reactions in the same patient. On day 4 of prophylaxis with nitrofurantoin 100 mg/day (to prevent urinary tract infections), the patient developed intense substernal pain and pressure. On day 8, she experienced intense substernal burning. She went to the emergency department, where she vomited and was hypotensive and febrile. Her chest radiograph showed bilateral infiltrates. The patient was diagnosed with pneumonia and was prescribed levofloxacin; she stopped taking the nitrofurantoin. Her symptoms subsided over the next 3 days. Ten days later, the patient restarted the nitrofurantoin, and she returned to the emergency department after again experiencing sudden intense substernal burning, nausea, vomiting, shivering, and weakness. Nitrofurantoin was discontinued; her symptoms resolved quickly, and prophylaxis with trimethoprim-sulfamethoxazole was begun. After 1 year, the patient had experienced no further pulmonary symptoms or urinary tract infections. Drug toxicity must be considered in patients who develop pulmonary symptoms while taking nitrofurantoin. Symptoms are often misdiagnosed as other ailments, potentially subjecting patients to unnecessary treatments and delaying discontinuation of nitrofurantoin. Patients should be advised to contact a physician if breathing difficulties or unusual symptoms develop while taking nitrofurantoin, as this could result in earlier recognition of this drug reaction.

Travel-related savings through a rural, clinic-based automated drug dispensing system.

For rural patients, access to pharmacies is often impeded by geographical and financial factors. The number of available pharmacies may be limited, and the extensive travel needed to access them is time consuming, potentially dangerous and, due to rising fuel prices, increasingly expensive. We describe the benefits of a clinic-based, automated medication dispensing system (ADDS) implemented in two rural communities in the Adirondack Mountain region of New York State. To estimate distance saved by utilizing the ADDS at the clinic, data from 268 consecutive patient encounters was imported into a mapping software package. Clinic Trip and Pharmacy Trip distances were calculated, with Miles saved estimated as the difference. Cost savings estimates were generated, with results reported as percentage of median per capita money income by county. Patients lived significantly closer to both clinics than to nearest traditional pharmacies, and saved an average travel distance of 32.6 and 18.0 miles per encounter. Cost estimates suggest travel-related savings of dollar 12.23 and dollar 6.75 per encounter, or 3.4% and 1.7% of weekly income. Considering the median out of pocket expense (dollar 13.31) for acquiring a prescription, patients traveling more than 35 miles round trip to obtain medications spent more on travel than on the medication itself. Placement of ADDS can significantly reduce the travel distances required for drug procurement in rural communities, and can provide acutely needed medications without travel-related delay. Such systems can provide considerable travel-related savings to the rural poor, where travel-related costs can exceed average drug costs.