Varenicline-associated acute renal failure.

OBJECTIVE: To report an association between acute renal failure and varenicline. CASE SUMMARY: A 53-year-old white male with preexisting moderate renal insufficiency was admitted to the hospital for acute renal failure following a change in serum creatinine from 4 mg/dL at baseline to 10.6 mg/dL upon admission. One week prior to admission, the patient started taking varenicline (dose undetermined) for smoking cessation and had been stable on all other medications for 2 months prior to admission. All hospital workup tests were negative for prerenal azotemia, postrenal obstruction, and intrinsic renal disease. Varenicline was discontinued on admission. With no other changes in therapy, the serum creatinine level decreased each day of the patient's 5-day hospitalization to 8.6 mg/dL upon discharge, and it was 6.4 mg/dL at a follow-up appointment 2 weeks after discharge. DISCUSSION: Varenicline is a novel medication that is effective for smoking cessation. Adverse effects are generally mild and self-limiting, with gastro-intestinal effects most commonly reported. According to the package insert, varenicline does not change creatinine clearance to any appreciable extent, but it should be used with caution in patients with renal impairment. It also states that varenicline can cause acute renal failure rarely; to our knowledge, this is the first published association of varenicline with renal effects. Use of the Naranjo probability scale showed varenicline to be the probable cause of renal dysfunction in this patient because of the temporal relationship and lack of alternative causes. CONCLUSIONS: Although there was a probable relationship between varenicline and acute renal failure in this patient, the significant benefit of smoking cessation to overall health outweighs the risk of this rare adverse effect. Clinicians should be aware of this potential adverse effect and should monitor renal function upon initiation of varenicline therapy, especially in patients with chronic kidney disease.

Improving effectiveness in communicating risk to patients.

OBJECTIVE: To review approaches and tools that pharmacists may use in communicating evidence of risk to older patients and their caregivers. DATA SOURCES: Relevant publications related to tools to communicate evidence to patients were identified through a systematic MEDLINE and Internet search engines using key words: evidence-based medicine/practice, patient, and risk communication. Additional articles were identified through use of the PubMed "related articles" feature and a review of citations of previously identified articles. STUDY SELECTION AND DATA EXTRACTION: Relevant English language publications were reviewed, with particular focus on articles about older adults. DATA SYNTHESIS: Communicating evidence from clinical trials to patients remains a challenge because of patient- and clinician-related barriers. Communicating with older adults faces additional challenges: perceptions of patient involvement in care and uncertainty of drug benefit-to-risk ratio because of the potential increase in adverse events. This is especially true in this population because of their multiple medical conditions. To actively involve patients in health care decisions, an ordered approach to teaching risks and benefits can be valuable. Evidence presented as a general risk estimate should be reinforced with specific numbers to depict patient-specific risk. Understanding may be strengthened with visual aids such as risk ladders or perspective scales. Each step in the process serves as a framework and should consider patients' individual values and beliefs. CONCLUSIONS: For patients to fully understand medications' risks and benefits, clinicians must use a systematic approach to present data from clinical trials and reinforce patients' comprehension using visual aids. Ultimately, these approaches and tools aim to support patient involvement in health care decisions.

Cilomilast: orally active selective phosphodiesterase-4 inhibitor for treatment of chronic obstructive pulmonary disease.

OBJECTIVE: To review available literature evaluating the pharmacology, pharmacokinetics, clinical efficacy, and adverse effects of cilomilast, a selective phosphodiesterase-4 (PDE4) inhibitor. DATA SOURCES: Literature was accessed through MEDLINE (1966-May 2006), Current Contents Clinical Medicine (1998-May 2006), and The Cochrane Library Database (1st quarter 2006) using the terms cilomilast, Ariflo, and SB 207 499. Reference lists from retrieved articles and information from the manufacturer were manually reviewed. STUDY SELECTION AND DATA EXTRACTION: All clinical trials evaluating cilomilast and published in English were included in this review. In addition, articles evaluating the pharmacology, pharmacokinetics, and safety of cilomilast in humans were reviewed. DATA SYNTHESIS: Cilomilast is a second-generation PDE4 inhibitor with antiinflammatory effects that target bronchoconstriction, mucus hypersecretion, and airway remodeling associated with chronic obstructive pulmonary disease (COPD). Selective PDE4 inhibition is proposed to maximize the antiinflammatory effects of PDE inhibition while minimizing the adverse effects of nonselective agents. To date, 4 clinical trials have evaluated the efficacy of cilomilast and demonstrated improvement in lung function (forced expiratory volume in 1 second) and quality of life and reduction in the occurrence of COPD exacerbations compared with placebo. Cilomilast is generally well tolerated, with adverse effects being overall mild and self-limiting. CONCLUSIONS: COPD is a progressive disease, and available treatment options provide limited efficacy. Given its unique mechanism of action and improved adverse effect profile compared with previous agents, cilomilast may have a promising role for the management of COPD.

Specific risk factors for Clostridium difficile-associated diarrhea: a prospective, multicenter, case control evaluation.

BACKGROUND: Clostridium difficile is a toxin-producing bacterium that is responsible for toxicity to the colonic mucosa, causing inflammation, necrosis, and, in some extreme cases, intestinal dilation and perforation. C difficile-associated diarrhea (CDAD) occurs when patients have a reduction in their natural gastrointestinal flora that allows for the proliferation of and toxin production by C difficile. METHODS: Using a multicenter, prospective observational case control study, we assessed and quantified risk factors associated with the development of diarrhea caused by Clostridium difficile, with particular attention to antibiotic use. All hospitalized patients with diarrhea requiring a C difficile toxin test as part of their routine clinical workup were considered for study inclusion. Patients with a negative specimen (controls) were considered for enrollment if matched (by age, sex, length of stay, and institution) to a case. Variables associated with CDAD were identified using univariate analysis. Significant factors were then entered into multivariate logistic regression analysis to identify independent factors. RESULTS: There were no significant differences in antibiotic use between cases and controls. Patient severity, classified by Horn's Index, was significantly different between cases and controls (P = .0022). No other significant variables were identified. CONCLUSION: The severity of illness of the cases was classified as more severe than the controls, but no significant differences in antibiotic use were identified between the groups. The negative C difficile toxin studies on the well-matched control patients indicate a different etiology of diarrhea (such as antibiotic-associated diarrhea), which may have developed in the presence of similar antibiotic use as the cases.

Optimal antithrombotic management of anticoagulated patients with a history of myocardial infarction.

A common clinical dilemma exists for optimal antithrombotic management of a patient requiring oral anticoagulation (such as venous thromboembolism) and continued secondary myocardial infarction prophylaxis. Often aspirin will be continued concomitantly with the indicated oral anticoagulation therapy; however, additional benefits and increased risks of this practice have not been established. A systematic literature review was conducted to determine the benefits and risks of antithrombotic treatment strategies. Five clinical trials met the inclusion criteria and were evaluated to answer this clinical question.

Integration of an introductory pharmacy practice experience with an advanced pharmacy practice experience in adult internal medicine.

OBJECTIVE: To describe the development, implementation, and assessment of an internal medicine introductory pharmacy practice experience (IPPE) that was integrated with an existing advanced pharmacy practice experience (APPE) in internal medicine. DESIGN: A structured IPPE was designed for first-, second-, and third-year pharmacy (P1, P2, and P3) students. Activities for the IPPE were based on the established APPE and the individual learner's educational level. ASSESSMENT: Students reported a greater understanding of clinical pharmacists' roles, increased confidence in their clinical skills, and better preparation for APPEs. Peers viewed the approach as innovative and transferable to other practice settings. Participating faculty members provided a greater number of contact hours compared to traditional one-time site visits. CONCLUSIONS: Integrating an IPPE with an existing APPE is an effective and efficient way to provide patient care experiences for students in the P1-P3 years in accordance with accreditation standards.

Stevens-Johnson syndrome associated with furosemide: a case report.

PURPOSE: To report a probable association of Stevens-Johnson Syndrome (SJS) with furosemide and suspected cross-sensitivity with lincomycin and silver sulfadiazine cream. SUMMARY: A 28-year-old Hispanic male was admitted for SJS, with a prolonged hospital course and unclear etiology throughout the majority of the stay. Patient's medications prior to development of SJS symptoms were stable for 3 months and with the exception of furosemide, all were continued throughout the hospitalization while the SJS resolved. During hospitalization, the patient was unintentionally rechallenged with furosemide, after which the rash reappeared and then worsened further with use of silver sulfadiazine cream. At this point in the hospitalization, the prolonged course of the rash prior to admission and the administration of lincomycin 3 days prior to admission were revealed. This suggests the SJS was initially caused by furosemide, a nonaromatic sulfonamide diuretic, with slow progression prior to hospital admission over approximately 7 weeks, followed by an acute worsening caused by lincomycin, a sulfide antibiotic. CONCLUSION: Use of the Naranjo ADR Probability Scale indicates a probable relationship between SJS and furosemide in this patient. Clinicians should be aware of this rare potential adverse effect, even months after the initiation of therapy.

Evaluating the impact of a pre-rotation workshop on student preparation for clinical advanced pharmacy practice experiences.

OBJECTIVES: This pilot study was designed to evaluate the impact of a pre-rotation workshop (PRW) on pharmacy students' clinical skills and preparation for clinical Advanced Pharmacy Practice Experiences (APPE) involving direct patient care. METHODS: Randomized controlled trial of an educational intervention with Institutional Review Board approval. PRW activities designed to simulate rotation activities around five competencies, patient charts, medication histories, SOAP notes, patient presentations, and professionalism. Endpoints were evaluated using clinical rotation preceptors' evaluation of performance and students' performance on objective structured clinical exams (OSCE). RESULTS: Eight fourth-year students and eight GPA matched controls (20% of the total class) were selected to voluntarily participate. The PRW demonstrated a positive impact on students' clinical skills and preparation for rotations by improving OSCE performance. However, no significant differences were found between groups when comparing preceptor evaluations of skills on rotations. These results are limited by the small sample size, potential OSCE "test-wiseness" effects, lack of OSCE evaluator blinding to study groups, potential case specificity effects due to the limited number of cases used on the OSCE and possible lack of sensitivity of the rotation evaluation tool to capture true differences among the experimental and control group participants. CONCLUSION: The PRW was successful at advancing students' clinical skills and preparation for rotations and may be considered as a tool to help bridge didactic to clinical experiences in the Pharm.D. curriculum.

Propofol-induced priapism, a case confirmed with rechallenge.

OBJECTIVE: To report a case of propofol-induced priapism. CASE SUMMARY: A 17-year-old male receiving propofol for induction of anesthesia during a cardiac ablation procedure developed priapism that required medical intervention and discontinuation of propofol. The priapism developed after a total propofol dose of 550 mg, lasted for 2 hours, and resolved immediately following medical intervention. The following day, the patient underwent a transesophageal echocardiogram and received a total propofol dose of 40 mg throughout the procedure. He again developed priapism, which resolved within one hour without medical intervention. DISCUSSION: Priapism experienced by this patient is considered to be drug-induced because of the temporal relationship, recurrence with rechallenge, and dose-response relationship. Using the Naranjo probability scale, we determined that propofol was a highly probable causative agent of priapism in this patient. CONCLUSIONS: Although, as of April 4, 2006, this adverse effect has not been previously reported, there is a strong correlation of propofol to priapism in this patient. Clinicians should be aware of this adverse effect.

Pantoprazole-induced thrombocytopenia.

OBJECTIVE: To report 2 cases of thrombocytopenia associated with pantoprazole treatment and discuss existing reports on this drug-induced adverse event. CASE SUMMARIES: This paper describes the course of thrombocytopenia associated with pantoprazole 40 mg in 2 hospitalized patients. In both cases, thrombocytopenia appeared after the initiation of pantoprazole and rapidly improved after discontinuation of pantoprazole, although complete resolution of thrombocytopenia occurred in only one patient prior to discharge from the hospital. DISCUSSION: The mechanism of drug-induced thrombocytopenia is often poorly understood, and proton-pump inhibitors are generally not strongly suspected as a cause of thrombocytopenia. However, an objective causality assessment using the Naranjo probability scale revealed a probable relationship between thrombocytopenia and pantoprazole in both of the cases. It is unknown whether this is a class effect. CONCLUSIONS: Although drug-induced thrombocytopenia with pantoprazole appears to be rare, it represents a potentially severe adverse effect. This supports the judicious prescribing of pantoprazole and possibly other proton-pump inhibitors.

Etoricoxib: a highly selective COX-2 inhibitor.

OBJECTIVE: To review the available literature evaluating the pharmacology, pharmacokinetics, clinical efficacy, and adverse effects of etoricoxib, a highly selective cyclooxygenase-2 (COX-2) inhibitor that is not currently approved for use in the US. DATA SOURCES: Literature retrieval was accessed through MEDLINE (1966-December 2004), Current Contents (1998-December 2004), and Cochrane Library (4th quarter 2004). References from retrieved articles, information from the manufacturer, and abstracts from the American College of Rheumatology and Annual European Congress of Rheumatology meetings were searched. STUDY SELECTION AND DATA EXTRACTION: All clinical trials published in English evaluating etoricoxib were included in this review. An abstract was excluded if it presented preliminary data from trials that are now published, analyzed data previously reported in a published clinical trial, or compared etoricoxib with placebo for an indication with published active-comparator controlled trials. DATA SYNTHESIS: Twelve clinical trials evaluating efficacy were reviewed. Efficacy for acute pain has been evaluated in acute gout, primary dysmenorrhea, and dental surgery and for chronic pain in rheumatoid arthritis, osteoarthritis, and chronic lower back pain. For safety, 3 clinical trials and 6 retrospective analyses of gastrointestinal, renovascular, or cardiovascular adverse effects were reviewed. CONCLUSIONS: Available studies demonstrate the efficacy of etoricoxib compared with nonsteroidal antiinflammatory drugs, but no published studies to date have compared etoricoxib with other selective COX-2 inhibitors. While these agents have demonstrated a significant reduction in gastrointestinal adverse effects, the cardiovascular adverse effects of selective COX-2 inhibition are not well defined. Further study is necessary to delineate the benefits and risks of etoricoxib compared with alternative treatment regimens.

Update in handheld electronic resources for evidence-based practice in the community setting.

OBJECTIVE: To provide an update on the handheld electronic resources for evidence-based practice (EBP) in the community setting. DATA SOURCES: Electronic resources for EBP in the community setting were identified by compiling the commonly used, well-established resources and by searching MEDLINE and other Internet sites. Search terms included evidence-based medicine, evidence-based practice, resources, and abstraction. Only sources available for personal digital assistants were included. DATA EXTRACTION: Three databases were identified that provided abstraction and evaluation of the medical literature for the handheld platform. Content, features, ease of use, system requirements, and costs of each resource were evaluated. DATA SYNTHESIS: FIRSTConsult, InfoRetriever, and UpToDate were evaluated, and the utility of each in the community pharmacy setting was evaluated by tracking a clinically relevant example through each system. FIRSTConsult provides evidence-based information organized by diagnosis but is not searchable on the handheld platform. InfoRetriever focuses on searchable evidence-based summaries, while UpToDate includes comprehensive topic reviews. The latter 2 platforms have large system memory requirements. All 3 sources provide evidence-based abstraction of the medical literature for the PDA platform, convenient for use at the point of care in community pharmacy. CONCLUSIONS: While users may select a particular resource based on unique features, each provides evidence-based abstraction of the medical literature that is a practical approach to EBP in the community pharmacy setting.

Valproic acid-induced neutropenia.

OBJECTIVE: To report a case of severe neutropenia caused by valproic acid (VPA). CASE SUMMARY: A 56-year-old white woman with an infectious brain abscess causing tonic-clonic seizure activity was treated with VPA. She developed severe neutropenia after 2 days of VPA therapy. The absolute neutrophil count reached a nadir of 47 cells/mm(3) during VPA use and returned to normal upon its discontinuation. DISCUSSION: VPA is considered to be a well-tolerated antiepileptic drug. While neutropenia has been reported, it has been mild and transient. This patient developed severe neutropenia during effective treatment with VPA, making her significantly susceptible to infection. The Naranjo probability scale indicates VPA as the probable cause of neutropenia in this case. CONCLUSIONS: This report of severe neutropenia caused by VPA emphasizes the importance of monitoring complete blood cell counts during therapy with this agent.

Evaluating the impact of a pre-rotation workshopon student preparation for clinical advancedpharmacy practice experiences

Objectives: This pilot study was designed to evaluate the impact of a pre-rotation workshop (PRW) on pharmacy students’ clinical skills and preparation for clinical Advanced Pharmacy Practice Experiences (APPE) involving direct patient care. Methods: Randomized controlled trial of an educational intervention with Institutional Review Board approval. PRW activities designed to simulate rotation activities around five competencies, patient charts, medication histories, SOAP notes, patient presentations, and professionalism. Endpoints were evaluated using clinical rotation preceptors’ evaluation of performance and students’ performance on objective structured clinical exams (OSCE). Results: Eight fourth-year students and eight GPA matched controls (20% of the total class) were selected to voluntarily participate. The PRW demonstrated a positive impact on students’ clinical skills and preparation for rotations by improving OSCE performance. However, no significant differences were found between groups when comparing preceptor evaluations of skills on rotations. These results are limited by the small sample size, potential OSCE “test-wiseness” effects, lack of OSCE evaluator blinding to study groups, potential case specificity effects due to the limited number of cases used on the OSCE and possible lack of sensitivity of the rotation evaluation tool to capture true differences among the experimental and control group participants. Conclusion: The PRW was successful at advancing students’ clinical skills and preparation for rotations and may be considered as a tool to help bridge didactic to clinical experiences in the Pharm.D. curriculum (AU)

Objetivos: Este estudio piloto se diseñó para evaluar el impacto de un taller pre-rotación (TPR) en las habilidades clínicas de los estudiantes de farmacia y en su preparación para las Practicas Clínicas Avanzadas de Farmacia (PAF) que envuelven atención directa al paciente. Métodos: Ensayo aleatorizado controlado de una intervención educativa con aprobación de la Junta de Revisión Institucional. Las actividades del TPR se diseñaron para simular las actividades de la rotación sobre 5 competencias: historias clínicas, historiales farmacoterapéuticos, notas SOAP, presentaciones de pacientes, y profesionalismo. Los resultados se evaluaron utilizando la evaluación de tutores de prácticas clínicas y exámenes clínicos estructurados objetivos (OSCE). Resultados: Se seleccionaron 8 estudiantes de cuarto año y 8 GPA controles emparejados (20% del total e la clase) para participar voluntariamente. El TPR demostró un impacto positivo en las habilidades clínicas de los estudiantes y en la preparación para sus rotaciones mejorando el desempeño en el OSCE. Sin embargo, no se encontraron diferencias significativas entre los grupos cuando se compararon las evaluaciones de los tutores de las habilidades en las rotaciones. Estos resultados están limitados por el pequeño tamaño de la muestra, posibles efectos de conocimiento de los exámenes OSCE, la falta de un evaluador OSCE ciego para los grupos de estudio, posibles especificidades de los casos debido al número limitado de casos usados en el OSCE, y posible falta de sensibilidad del instrumento de evaluación de la rotación para encontrar verdaderas diferencias entre los grupos control e intervención. Conclusión: El TPR tuvo éxito en aumentar las habilidades clínicas de los estudiantes y la preparación para la rotaciones, y podría considerarse una herramienta para reducir la brecha didáctica a la práctica clínica en el currículo de Doctor en Farmacia (AU)