An open-label, pragmatic, randomized controlled clinical trial to evaluate the comparative effectiveness of daptomycin versus vancomycin for the treatment of complicated skin and skin structure infection.

BACKGROUND: Treatment of complicated skin and skin structure infection (cSSSI) places a tremendous burden on the health care system. Understanding relative resource utilization associated with different antimicrobials is important for decision making by patients, health care providers, and payers. METHODS: The authors conducted an open-label, pragmatic, randomized (1:1) clinical study (N = 250) to compare the effectiveness of daptomycin with that of vancomycin for treatment of patients hospitalized with cSSSI caused by suspected or documented methicillin-resistant Staphylococcus aureus infection. The primary study end point was infection-related length of stay (IRLOS). Secondary end points included health care resource utilization, cost, clinical response, and patient-reported outcomes. Patient assessments were performed daily until the end of antibiotic therapy or until hospital discharge, and at 14 days and 30 days after discharge. RESULTS: No difference was found for IRLOS, total LOS, and total inpatient cost between cohorts. Hospital LOS contributed 85.9% to the total hospitalization cost, compared with 6.4% for drug costs. Daptomycin showed a nonsignificant trend toward a higher clinical success rate, compared with vancomycin, at treatment days 2 and 3. In the multivariate analyses, vancomycin was associated with a lower likelihood of day 2 clinical success (odds ratio [OR] = 0.498, 95% confidence interval [CI], 0.249-0.997; P < 0.05). CONCLUSION: This study did not provide conclusive evidence of the superiority of one treatment over the other in terms of clinical, economic, or patient outcomes. The data suggest that physician and patient preference, rather than drug acquisition cost, should be the primary driver of initial antibiotic selection for hospitalized patients with cSSSI. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01419184 (Date: August 16, 2011).

Investigation of Simulated Pharmacist Decision Making Involving Prescriptions With a High Probability of Causing Patient Harm.

Background: Medication errors pose a significant risk to patients, resulting in morbidity, mortality, and unnecessary health care utilization. Pharmacists, using their professional judgment, have an important role as a final check for identifying and resolving these problems. Little is known, however, about pharmacist perspectives and experiences with dispensing or withholding potentially dangerous prescriptions. Objectives: To (a) evaluate the extent to which pharmacists would not dispense a likely harmful prescription which has been confirmed by the prescriber and (b) assess pharmacist attitudes and experiences with dispensing likely harmful prescriptions. Methods: An anonymous, self-administered, 25-item survey was emailed to members of a state pharmacy association and a pharmacy college alumni list. A series of static prescription vignettes (1 reasonable and 4 likely dangerous doses) were presented and asked if they would fill each prescriber-confirmed prescription. Pharmacists also were asked a series of Likert-type, open-ended, multiple choice, and demographic items regarding their professional experiences and role perceptions. Results: There were 497 usable responses. Three of the 4 dangerous prescriptions were withheld by the majority of pharmacists (sumatriptan as the exception). No demographic variable was universally associated with filling dangerous vignette prescriptions; rather, there were vignette-specific differences. The majority of pharmacists reported refusing to fill a potentially harmful prescription during their career. Conclusions: There appears to be meaningful variation in how pharmacists react when presented with likely harmful prescriptions. More research is needed to better understand this role, its determinants, and the potential effects on patient safety.

Community Pharmacist and Family Medicine Collaboration for Pre-Visit Planning for Shared Patients Receiving Chronic Care Management Services.

Background: Pre-visit planning entails completing necessary tasks prior to clinic appointments. Community pharmacists (CPs) have unique knowledge about patients' medication use but do not routinely provide drug therapy reviews before clinic visits. Objectives: (1) Create and implement a business partnership between a CP and family medicine clinic (FMC) for CP provision of pre-visit medication reviews, and (2) describe the billing experience for shared patients in the FMC chronic care management (CCM) program. Methods: A prospective 8-month study in one community pharmacy and FMC in Iowa. Eligible patients were enrolled in the clinic CCM program and received their prescriptions at the CP. CPs were granted access to the clinic electronic health record (EHR), performed medication reviews, and recorded drug therapy recommendations (DTRs) in the clinic EHR. FMC physicians reviewed CP DTRs before the patient encounter. Time tracking software in the EHR recorded CP and FMC time performing CCM services. CCM revenue was prorated between parties. FMC physicians completed a survey about their experience. Results: Overall, there were 129 CP reviews performed for 95 patients. These reviews resulted in 169 DTRs and 76% were accepted by the physician. There were 71 CCM claims billed and CCM revenue was $3596 ($1796 FMC, $1800 CP). More than 90% of physicians (N = 11) indicated they reviewed CP DTRs before the patient encounter and agreed they were helpful to their practice. Conclusion: CPs completed pre-visit medication reviews and made accepted medication therapy recommendations. CCM billing provided a mechanism for CPs to receive revenue for their services.

A prospective, multi-center cohort study: investigating the ability of warfarin-treated patients to predict their INR.

BACKGROUND: In practice, warfarin-treated patients may share insight regarding their international normalized ratio (INR) value before it is measured. The accuracy and potential utility of these predictions have not been evaluated. OBJECTIVE: To (1) test how accurately patients can predict their INR; (2) identify demographic factors associated with their ability to predict their INR accurately; and (3) identify demographic factors associated with the patient's INR being in the therapeutic range. METHODS: A prospective, multi-center cohort study enrolled patients from eight anticoagulation clinics in Iowa. Inclusion criteria were: age ≥ 18 years, warfarin use ≥ 60 days, INR goal of 2.0-3.0, and expected warfarin use > 6 months. Subjects completed a data collection form during enrollment and before each INR measurement. Data included demographics, a set of medication taking beliefs and practices, self-reported adherence, past INR values, INR prediction and reason(s) for the prediction. RESULTS: There were 87 subjects enrolled with 372 INR measurements. The mean (SD) number of INRs per subject was 4.3 (1.8). Thirty percent of subjects reported they could tell when their INR is out of goal range. Patients predicted that 90.5% of their INRs would be within goal range, although only 65.5% of INRs were therapeutic. Patients correctly predicted a low INR as low or high INR as high in only 9.4% of out of range instances. A set of demographic characteristics and medication beliefs were not associated with prediction accuracy or percentage of INR measurements in range (PINRR). Most patients did not give a reason for their predicted result. For those that did, the most common factor was perceived stability at current dose. CONCLUSION: While some patients believed they could predict when their INR was out of range, only few were able to do so. Most patients assumed a therapeutic INR and missed when their INR was high or low. Patients should be advised against modifying their warfarin dose without consulting the provider that manages their therapy. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT 02764112.

Pharmacist Intervention for Blood Pressure Control in Patients with Diabetes and/or Chronic Kidney Disease.

OBJECTIVES: The objectives of this study were to determine if hypertensive patients with comorbid diabetes mellitus (DM) and/or chronic kidney disease (CKD) receiving a pharmacist intervention had a greater reduction in mean blood pressure (BP) and improved BP control at 9 months compared with those receiving usual care; and compare Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) guideline and 2014 guideline (JNC 8) BP control rates in patients with DM and/or CKD. METHODS: This cluster randomized trial included 32 medical offices in 15 states. Clinical pharmacists made treatment recommendations to physicians at intervention sites. This post hoc analysis evaluated mean BP and BP control rates in the intervention and control groups. MAIN RESULTS: The study included 335 patients (227 intervention, 108 control) when mean BP and control rates were evaluated by JNC 7 inclusion and control criteria. When JNC 8 inclusion and control criteria were applied, 241 patients (165 intervention, 76 control) remained and were included in the analysis. The pharmacist-intervention group had significantly greater mean systolic blood pressure reduction compared with usual care at 9 months (8.64 mm Hg; 95% confidence interval [CI] -12.8 to -4.49, p<0.001). The pharmacist-intervention group had significantly higher BP control at 9 months than usual care by either the JNC 7 or JNC 8 inclusion and control groups (adjusted odds ratio [OR] 1.97, 95% CI 1.01-3.86, p=0.0470 and OR 2.16, 95% CI 1.21-3.85, p=0.0102, respectively). PRINCIPAL CONCLUSIONS: This study demonstrated that a physician-pharmacist collaborative intervention was effective in reducing mean systolic BP and improving BP control in patients with uncontrolled hypertension with DM and/or CKD, regardless of which BP guidelines were used.

Adherence to clinical practice guidelines for 7 chronic conditions in long-term-care patients who received pharmacist disease management services versus traditional drug regimen review.

BACKGROUND: Numerous studies have shown that adherence to published clinical practice guidelines (CPGs) reduces disease morbidity and mortality. However, few benchmarks exist that demonstrate the rate of adherence to CPGs in patients in long-term-care facilities (LTCFs). OBJECTIVE: To evaluate CPG adherence in patients in LTCFs who received consultation from pharmacists who emphasize disease state management (DSM) compared with patients in other LTCFs who received traditional drug regimen review (DRR). METHODS: A retrospective chart review was conducted in November 2005 for 107 patients who received DSM services in 2 LTCFs and 304 patients who received DRR services in 4 LTCFs for the service period ending September 30, 2005. Chart review was conducted on all patients included in the current census as of September 1, 2005; residents were excluded from the analysis if they were discharged or deceased between September 1, 2005, and the date of chart review. CPG adherence was evaluated for the following 7 conditions: diabetes, coronary artery disease (CAD), stroke, heart failure (HF), hypertension, hyperlipidemia, and osteoporosis. In addition, the 6 most recent pharmacist recommendations for each patient were classified according to disease state. RESULTS: Adherence to CPGs was significantly better (all P <0.05) in patients receiving DSM services for the following performance measures for 4 of the 7 disease states: (1) diabetes: antiplatelet or warfarin use or contraindication for use (hypersensitivity or history of serious bleeding event), 89.7% for DSM services versus 71.0% for DRR services, and glycosylated hemoglobin (HbA1c) 0.05). The mean number of pharmacist recommendations per patient per month was greater in DSM facilities (0.76) compared with DRR facilities (0.23, P <0.001). Pharmacists who provided DSM consultant services were more likely to make a recommendation to improve DSM (51.6%) than were pharmacists in the comparison facilities who provided traditional DRR services (31.7%, P <0.001). CONCLUSION: This self-evaluation of the provision of pharmacist consultant services that focus on disease management in addition to DRR found a higher rate of adherence to clinical practice guidelines for 4 of 7 common chronic disease states in long-term-care patients compared with patients who received only traditional DRR services.

Assessment of postgraduate skin lesion education among Iowa family physicians.

BACKGROUND: Family medicine physicians play a pivotal role in the prevention and early detection of skin cancer. Our objective was to evaluate how family physicians believe their postgraduate training in skin cancer screening and prevention has prepared them for independent practice and to assess the need for enhanced skin lesion teaching in a family medicine residency setting. METHODS: A descriptive, cross-sectional survey investigating provider demographics, confidence in providing dermatological care, residency training, current medical practice, and skin cancer prevention beliefs was mailed to all family medicine physicians in the state of Iowa as listed in the Iowa Academy of Family Physicians annual directory in 2006 (N = 1069). RESULTS: A total of 575 family medicine physicians completed the survey for an overall response rate of 53.8%. Overall, family medicine physicians reported feeling confident in their ability to diagnose skin lesions (83.2%), differentiate between benign and malignant lesions (85.3%), and perform a biopsy of a lesion (94.3%). Only 65% of surveyed physicians felt that their residency program adequately trained them in diagnosing skin lesions and 65.7% of physicians agree that they could have benefited from additional training on skin lesions during residency training. Nearly 90% of clinicians surveyed believe that skin cancer screenings are the standard of care; however, only 51.8% perform skin cancer screening examinations during adult health maintenance visits more than 75% of the time. The primary reason listed by respondents who said they do not routinely perform skin cancer screenings was inadequate time (68.2%). CONCLUSION: Family medicine physicians in the state of Iowa are confident in evaluating skin lesions. However, they reported a need for additional enhanced, targeted skin lesion education in family medicine residency training programs. Physicians believe that skin cancer screening examination is the standard of care, but find that inadequate time increasingly hinders skin cancer screening during routine health maintenance examinations.

Inclusion of salt form on prescription medication labeling as a source of patient confusion: a pilot study.

BACKGROUND: It has been estimated that 10,000 patient injuries occur in the US annually due to confusion involving drug names. An unexplored source of patient misunderstandings may be medication salt forms. OBJECTIVE: The objective of this study was to assess patient knowledge and comprehension regarding the salt forms of medications as a potential source of medication errors. METHODS: A 12 item questionnaire which assessed patient knowledge of medication names on prescription labels was administered to a convenience sample of patients presenting to a family practice clinic. Descriptive statistics were calculated and multivariate analyses were performed. RESULTS: There were 308 responses. Overall, 41% of patients agreed they find their medication names confusing. Participants correctly answered to salt form questions between 12.1% and 56.9% of the time. Taking more prescription medications and higher education level were positively associated with providing more correct answers to 3 medication salt form knowledge questions, while age was negatively associated. CONCLUSIONS: Patient misconceptions about medication salt forms are common. These findings support recommendations to standardize the inclusion or exclusion of salt forms. Increasing patient education is another possible approach to reducing confusion.

Women's quality of life is decreased by acute cystitis and antibiotic adverse effects associated with treatment.

BACKGROUND: Although acute cystitis is a common infection in women, the impact of this infection and its treatment on women's quality of life (QOL) has not been previously described. OBJECTIVES: To evaluate QOL in women treated for acute cystitis, and describe the relationship between QOL, clinical outcome and adverse events of each of the interventions used in the study. DESIGN: Randomized, open-label, multicenter, treatment study. SETTING: Two family medicine outpatient clinics in Iowa. PATIENTS: One-hundred-fifty-seven women with clinical signs and symptoms of acute uncomplicated cystitis. INTERVENTION: Fifty-two patients received trimethoprim/sulfamethoxazole 1 double-strength tablet twice daily for 3 days, 54 patients received ciprofloxacin 250 mg twice daily for 3 days and 51 patients received nitrofurantoin 100 mg twice daily for 7 days. MEASUREMENTS: QOL was assessed at the time of enrollment and at 3, 7, 14 and 28 days after the initial visit. QOL was measured using a modified Quality of Well-Being scale, a validated, multi-attribute health scale. Clinical outcome was assessed by telephone interview on days 3, 7, 14 and 28 using a standardized questionnaire to assess resolution of symptoms, compliance with the prescribed regimen, and occurrence of adverse events. RESULTS: Patients experiencing a clinical cure had significantly better QOL at days 3 (p = 0.03), 7 (p < 0.001), and 14 (p = 0.02) compared to patients who failed treatment. While there was no difference in QOL by treatment assignment, patients experiencing an adverse event had lower QOL throughout the study period. Patients treated with ciprofloxacin appeared to experience adverse events at a higher rate (62%) compared to those treated with TMP/SMX (45%) and nitrofurantoin (49%), however the difference was not statistically significant (p = 0.2). CONCLUSION: Patients experiencing cystitis have an increase in their QOL with treatment. Those experiencing clinical cure have greater improvement in QOL compared to patients fail therapy. While QOL is improved by treatment, those reporting adverse events have lower overall QOL compared to those who do not experience adverse events. This study is important in that it suggests that both cystitis and antibiotic treatment can affect QOL in a measurable way.

Suggested guidelines for pharmacotherapy curricula in family medicine residency training: recommendations from the Society of Teachers of Family Medicine Group on Pharmacotherapy.

Rational drug use has increasingly received public policy attention in efforts to maintain quality health care at lower costs. Prescribing habits are developed during residency training, and education regarding rational drug use should be an integral part of the residency curricula. Considering that many medical errors in family medicine are related to incorrect medication management, there is need for a focused education in pharmacotherapy. This paper outlines suggested guidelines for pharmacotherapy curricula in family medicine residency training, as recommended by the Society of Teachers of Family Medicine Group on Pharmacotherapy. A pharmacotherapy curriculum should include common conditions managed in family medicine, as well as general principles of pharmacotherapy. This should allow for repeated exposure to core topics over a 3-year cycle and be delivered in various settings (didactic teaching, longitudinal active learning, point-of-care education, and rotations). The curriculum should apply and evaluate pharmacotherapy education according to the six core competencies of the Accreditation Council for Graduate Medical Education (ACGME). Although physician faculty can be responsible for pharmacotherapy education, a clinical pharmacist is uniquely qualified to provide this service. Overall, family medicine residents need comprehensive instruction in pharmacotherapy to develop rational prescribing habits. A structured pharmacotherapy curriculum may assist in achieving this goal and in meeting the ACGME core competencies for residency training.

Achieving the best outcome in treatment of depression.

Combined treatment with psychotherapy or psychiatric consult and drug therapy has shown better response in several studies than either therapy alone. Although not proven by clinical trials, selecting a medication by matching its side-effect profile to patient characteristics is supported by case reports and likely enhances compliance. Patients who do not improve with initial therapy often benefit from being switched to another class of antidepressants, or having a drug from another class added to their therapy.

A lifestyle intervention study in patients with diabetes or impaired glucose tolerance: translation of a research intervention into practice.

OBJECTIVE: The objectives of this study were to translate a research-validated lifestyle modification curriculum of the Diabetes Prevention Program (DPP) into a community-based program delivered by trained graduate students on a university campus and determine whether this delivery approach is effective in lowering risk factors of type 2 diabetes in at-risk adults. METHODS: A convenience sample of 29 prediabetic or type 2 diabetic patients completed a 12-month behavior modification intervention to achieve and maintain at least 7% weight loss and become more active. Changes in weight, waist and hip circumferences, blood pressure, metabolic biomarkers, physical activity levels, and medication were assessed. RESULTS: At 6 and 12 months, 39% and 56% of patients had lost > or =5% of their weight. The mean weight loss at 12 months was 6%. Significant improvements were noted in most other anthropometric measurements and diastolic BP (-4.1 mm Hg). Significant reductions in total cholesterol (-11.7%), LDL-C (-7.6%), and HDL-C (-6.5%) were observed by 6 months but not at 12 months. Fasting glucose (-12%), systolic BP (-8.4 mm Hg), and diastolic BP (-7.0 mm Hg) were significantly improved in a subgroup of participants with at least 5% weight loss. HbA1c levels were associated with percentage weight loss. Twenty-seven percent of participants on diabetes medication had their drug discontinued. CONCLUSION: Weight-related findings of this study are comparable with those of the DPP. DPP curriculum implemented in a nonclinical setting can help some adults at-risk for or in early stages of diabetes improve anthropometric and certain metabolic outcomes.

Severe rhabdomyolysis and acute renal failure secondary to concomitant use of simvastatin, amiodarone, and atazanavir.

OBJECTIVE: To report a case of a severe interaction between simvastatin, amiodarone, and atazanavir resulting in rhabdomyolysis and acute renal failure. BACKGROUND: A 72-year-old white man with underlying human immunodeficiency virus, atrial fibrillation, coronary artery disease, and hyperlipidemia presented with generalized pain, fatigue, and dark orange urine for 3 days. The patient was taking 80 mg simvastatin at bedtime (initiated 27 days earlier); amiodarone at a dose of 400 mg daily for 7 days, then 200 mg daily (initiated 19 days earlier); and 400 mg atazanavir daily (initiated at least 2 years previously). Laboratory evaluation revealed 66,680 U/L creatine kinase, 93 mg/dL blood urea nitrogen, 4.6 mg/dL creatinine, 1579 U/L aspartate aminotransferase, and 738 U/L alanine aminotransferase. Simvastatin, amiodarone, and the patient's human immunodeficiency virus medications were all temporarily discontinued and the patient was given forced alkaline diuresis and started on dialysis. Nine days later the patient's creatine kinase had dropped to 1695 U/L and creatinine was 3.3 mg/dL. The patient was discharged and continued outpatient dialysis for 1 month until his renal function recovered. DISCUSSION: The risk of rhabdomyolysis is increased in the presence of concomitant drugs that inhibit simvastatin metabolism. Simvastatin is metabolized by CYP3A4. Amiodarone and atazanavir are recognized CYP3A4 inhibitors. CONCLUSIONS: Pharmacokinetic differences in statins are an important consideration for assessing the risk of potential drug interactions. In patients requiring the concurrent use of statins and CYP3A4 inhibitors, pravastatin, fluvastatin, and rosuvastatin carry the lowest risk of drug interactions; atorvastatin carries moderate risk, whereas simvastatin and lovastatin have the highest risk and should be avoided in patients taking concomitant CYP3A4 inhibitors.

Antimuscarinic intoxication resulting from the ingestion of moonflower seeds.

OBJECTIVE: To report a case in which ingestion of moonflower seeds resulted in antimuscarinic intoxication. CASE SUMMARY: An 18-year-old man was found at a local convenience store hallucinating and incoherent. Upon presentation to the emergency department, his signs and symptoms included tachycardia, confusion, dilated pupils, and dry, flushed, hot skin. He was admitted to the intensive care unit. Hallucinations and symptoms resolved within 36-48 hours after hospitalization. The patient then reported that he had ingested moonflower seeds. He recovered and was released 4 days after admission. DISCUSSION: Based on the patient's description and clinical presentation, the moonflower seeds were believed to be Datura inoxia. This species of plant is similar to jimson weed, or Datura stramonium. These plants are known to contain high concentrations of anticholinergic substances; ingestion can result in anticholinergic intoxication. Signs and symptoms that commonly occur include hallucinations, tachycardia, dilated pupils, and disorientation. In our patient, use of the Naranjo probability scale indicated a possible relationship between the moonflower seed ingestion and the patient's signs and symptoms. CONCLUSIONS: Ingestion of the Datura species can result in severe toxicity. Each plant varies in the concentrations of alkaloid substances. For this reason, it is very important for individuals to become educated on the toxicities and potential risks associated with recreational use of these plants.

Analgesic efficacy of calcitonin for vertebral fracture pain.

OBJECTIVE: To evaluate the analgesic efficacy of calcitonin for treating the pain of vertebral fractures associated with osteoporosis. DATA SOURCES: Searches of MEDLINE (1966-July 2002), Cochrane Library, International Pharmaceutical Abstracts (1977-July 2002), and an extensive manual review of journals were performed using the key search terms calcitonin, analgesic, osteoporosis, vertebral fracture, and pain. STUDY SELECTION AND DATA EXTRACTION: All articles identified from the data sources were evaluated and all information deemed relevant was included for this review. DATA SYNTHESIS: Fractures, especially vertebral fractures, are a common complication of osteoporosis, leading to significant pain. Calcitonin has been studied for its analgesic properties. Fourteen double-blind, placebo-controlled trials that evaluated the analgesic efficacy of calcitonin for osteoporosis-related vertebral fracture pain were identified and reviewed. Thirteen of these studies demonstrated statistically significant improvement in pain or function in calcitonin-treated patients. CONCLUSIONS: Calcitonin has proven efficacy in acute pain associated with osteoporosis-related vertebral fractures. Analgesic effects are seen with intranasal, parenteral, and rectal administration. Future studies comparing calcitonin with other commonly used analgesics are needed to more clearly define its place in therapy.

Oral antivirals for the acute treatment of recurrent herpes labialis.

OBJECTIVE: To evaluate the use and benefit of oral antivirals in the acute treatment of episodic, recurrent herpes labialis. DATA SOURCES: A literature search was performed in MEDLINE (1966-August 2003) using acyclovir, famciclovir, valacyclovir, cold sores, herpes labialis, and HSV-1 as search terms. DATA SYNTHESIS: We reviewed 5 placebo-controlled and 2 comparative studies evaluating oral antivirals for acute treatment of recurrent herpes labialis. No studies directly compared different antivirals. Studies discussing the efficacy of antivirals for chronic suppression of herpes simplex virus-1 infection were not included. CONCLUSIONS: Treatment with oral antivirals decreases the duration of lesion episodes and pain by approximately one day; however, the antivirals do not abort lesions from developing. Clinical implications of these results appear relatively modest.

Fatal aspiration pneumonia during transition from donepezil to rivastigmine.

OBJECTIVE: To report a case of fatal aspiration pneumonia in a patient shortly after initiation of rivastigmine and discontinuation of donepezil, with no washout period between therapies. CASE SUMMARY: An 83-year-old white man presented to the emergency department in respiratory distress (O2 saturation 70%; RR 44 breaths/min) secondary to aspiration. He had started rivastigmine 1.5 mg twice daily that same day. The patient had been previously treated with donepezil 10 mg/d, and there was no washout period. He was intubated due to worsening respiratory status and was transferred to the cardiac care unit. He then became hypotensive and required dopamine and fluid support. Brief bronchoscopy revealed food particles in the lower airways and bile-stained secretions. Intubation was notable for the large amount of secretions. The patient died approximately 27 hours after presentation to the emergency department. Blood and sputum cultures were subsequently positive for Haemophilus influenzae. DISCUSSION: Cholinesterase (ChE) inhibitors approved for treatment of Alzheimer disease are associated with nausea and vomiting in a sizable percentage of patients, ranging from 5% to 31% in clinical trials. Most of these adverse events occur during the initiation/titration phase of therapy. An additive risk of adverse events may be expected with coadministration of ChE inhibitors or cholinergic agents or, potentially, with an inadequate washout period between such agents. Review of MEDLINE (1966-July 2002) and International Pharmaceutical Abstracts (1970-July 2002) failed to identify any previous reports of aspiration with rivastigmine or donepezil. CONCLUSIONS: A washout period should be considered when switching between ChE inhibitors to minimize the risk of vomiting and aspiration.