Edaravone Oral Suspension: A Neuroprotective Agent to Treat Amyotrophic Lateral Sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is characterized by loss of motor neurons due to degeneration of nerve cells within the brain and spinal cord. Early symptoms include limb weakness, twitching or muscle cramping, and slurred speech. As the disease progresses, difficulty breathing, swallowing, and paralysis can lead to death. Currently, there are no medications that cure ALS, and guidelines recommend treatments focused on symptom management. Intravenous (IV) edaravone was approved by the US Food and Drug Administration (FDA) in 2017 as a treatment to slow the progression of ALS. In May 2022, the FDA approved an oral suspension (ORS) formulation of edaravone. MECHANISM OF ACTION: The mechanism of action of edaravone is not well defined. However, its neuroprotective effects are thought to result from antioxidant properties occurring through elimination of free radicals. PHARMACOKINETICS: Edaravone ORS (105 mg) has a bioavailability of 57% when compared with edaravone IV (60 mg). The ORS should be taken on an empty stomach in the morning, with water and no food or beverages, for 1 hour. Edaravone is bound to albumin (92%), has a mean volume of distribution of 63.1 L, a half-life of 4.5-9 hours, and a total clearance of 35.9 L/h after intravenous administration. Edaravone is metabolized into nonactive sulfate and glucuronide conjugates. CLINICAL TRIALS: The FDA approval was based on studies of the pharmacokinetics, safety, tolerability, and bioavailability of edaravone ORS. A phase III, global, multicenter, open-label safety study was conducted on edaravone ORS in 185 patients with ALS over 48 weeks. The most reported treatment-emergent adverse events were falls, muscular weakness, and constipation. Serious treatment-emergent adverse events included disease worsening, dysphagia, dyspnea, and respiratory failure. THERAPEUTIC ADVANCE: Oral edaravone is an ALS treatment that can be self-administered or administered by a caregiver, precluding the need for administration by a health care professional in an institutional setting.

Transthyretin Amyloid Cardiomyopathy-Current and Future Therapies.

OBJECTIVE: To describe the clinical presentation of transthyretin amyloid cardiomyopathy (ATTR-CM) and discuss current treatments and investigational products and their effect on patient outcomes. DATA SOURCES: A literature search was performed in PubMed (September 2018 to December 2020) using the following keywords: transthyretin amyloidosis, cardiomyopathy, polyneuropathy and transthyretin amyloid cardiomyopathy, monoclonal light-chain, tafamidis, cardiac amyloidosis, ATTR cardiomyopathy, green tea and inhibition of cardiac amyloidosis, AG10, tolcapone, tolcapone and leptomeningeal ATTR, PRX004, NI006, patisiran, inotersen, vutrisiran, AKCEA-TTR-LRx, and NTLA-2001. STUDY SELECTION AND DATA EXTRACTION: Clinical trials were evaluated for evidence supporting pharmacology, safety, efficacy, and measured outcomes. DATA SYNTHESIS: Until 2019, there were no approved treatments for ATTR-CM. Treatment consisted of symptom management and organ transplant. Nonpharmacological and pharmacological treatments focused on the symptoms of heart failure (HF) associated with ATTR-CM. However, there are several emerging therapies recently approved or in development to address the underlying pathophysiology. Treatment classes for ATTR-CM include transthyretin stabilizers, human monoclonal antibodies, gene silencers, and CRISPR/Cas9 gene editing. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: ATTR-CM is a complex disease in which amyloidosis causes cardiomyopathy. Underdiagnosis is attributed to the clinical presentation being heterogeneous, indistinguishable from HF caused by other etiologies, and the need for invasive testing modalities, including endomyocardial biopsy. Improved diagnostic approaches along with targeted therapies can slow disease progression and enhance patient quality of life. CONCLUSION: Diagnostic modalities along with biomarker and genetic testing could detect disease earlier and target therapy more accurately. Novel therapies demonstrate potential treatment benefits and can help shape the standard of care for these patients.

The Surgical Skills and Technology Elective Program (SSTEP): A comprehensive simulation-based surgical skills initiative for preclerkship medical students.

BACKGROUND: The Surgical Skills and Technology Elective Program (SSTEP) is a voluntary preclerkship surgical bootcamp that uses simulation learning to build procedural knowledge and technical skills before clerkship. METHODS: Eighteen second year students (n = 18) participated in simulation workshops over the course of 7 days to learn clerkship-level procedural skills. A manual was supplied with the program outline. Assessment of the participants involved: 1) a written exam 2) a single videotaped Objective Structured Assessment of Technical Skill (OSATS) station 3) an exit survey to document changes in career choices. RESULTS: Compared to the mean written pre-test score students scored significantly higher on the written post-test (35.83 ± 6.56 vs. 52.11 ± 5.95 out of 73) (p = 0.01). Technical skill on the OSATS station demonstrated improved performance and confidence following the program (10.10 vs. 17.94 out of 25) (p = 0.05). Most participants (72%) re-considered their choices of surgical electives. CONCLUSIONS: A preclerkship surgical skills program not only stimulates interest in surgery but can also improve surgical knowledge and technical skills prior to clerkship.

Vancomycin Dosing in Obese Patients: Special Considerations and Novel Dosing Strategies.

OBJECTIVE: To review the literature regarding vancomycin pharmacokinetics in obese patients and strategies used to improve dosing in this population. DATA SOURCES: PubMed, EMBASE (1974 to November 2017), and Google Scholar searches were conducted using the search terms vancomycin, obese, obesity, pharmacokinetics, strategy, and dosing. Additional articles were selected from reference lists of selected studies. STUDY SELECTION AND DATA EXTRACTION: Included articles were those published in English with a primary focus on vancomycin pharmacokinetic parameters in obese patients and practical vancomycin dosing strategies, clinical experiences, or challenges of dosing vancomycin in this population. DATA SYNTHESIS: Volume of distribution and clearance are the pharmacokinetic parameters that most often affect vancomycin dosing in obese patients; both are increased in this population. Challenges with dosing in obese patients include inconsistent and inadequate dosing, observations that the obese population may not be homogeneous, and reports of an increased likelihood of supratherapeutic trough concentrations. Investigators have revised and developed dosing and monitoring protocols to address these challenges. These approaches improved target trough attainment to varying degrees. CONCLUSIONS: Some of the vancomycin dosing approaches provided promising results in obese patients, but there were notable differences in methods used to develop these approaches, and sample sizes were small. Although some approaches can be considered for validation in individual institutions, further research is warranted. This may include validating approaches in larger populations with narrower obesity severity ranges, investigating target attainment in indication-specific target ranges, and evaluating the impact of different dosing weights and methods of creatinine clearance calculation.

Incorporating the American Pharmacists Association's Delivering Medication Therapy Management services certificate program into an accelerated pharmacy curriculum.

BACKGROUND AND PURPOSE: To describe the incorporation of the American Pharmacists Association (APhA) Delivering Medication Therapy Management (MTM) Services program into a PharmD curriculum and to describe student perceptions of the program. EDUCATIONAL ACTIVITY AND SETTING: The program was delivered over 12 months to students on two campuses via two didactic courses in the second professional year and during the first two advanced pharmacy practice experiences in the third professional year of an accelerated school of pharmacy program. FINDINGS: Student perceptions were assessed by review of responses to the APhA MTM program evaluation survey. DISCUSSION AND SUMMARY: Incorporation of the APhA MTM program into an accelerated PharmD program required careful planning and coordination amongst faculty and course coordinators. Students perceived that the program was valuable, met their educational needs, and incorporated effective learning experiences and cases. These perceptions were reinforced by the high percentage of students who completed the program.

Oritavancin: A Novel Lipoglycopeptide.

OBJECTIVE: To review the pharmacology, pharmacokinetics, drug interactions, microbiologic profile, dosage and administration, safety, clinical efficacy, and potential place in therapy for the new lipoglycopetide, oritavancin. DATA SOURCES: MEDLINE and PubMed searches of available literature in English were conducted for oritavancin. Principal supplementary sources include the Food and Drug Administration (FDA) package insert, and FDA/European Medicines Agency guidances on acute bacterial skin and skin structure infections (ABSSSI). STUDY SELECTION AND DATA EXTRACTION: Information from all stages of clinical development was evaluated to provide an overview of oritavancin, from in vitro susceptibility, to early human studies, to the latter stages of clinical trials. DATA SYNTHESIS: Oritavancin is a lipoglycopeptide antibiotic that has a mechanism of action and broad-spectrum gram-positive coverage similar to other glycopeptides. Compared with other glycopeptides, oritavancin minimum inhibitory concentrations tend to be lower. Oritavancin also has coverage against glycopeptide-resistant gram-positive organisms. Oritavancin does not require dose adjustment for mild-to-moderate hepatic or renal impairment, and its prolonged half-life of 245 hours allows for a one-time administration in the treatment of ABSSSI. In phase 2 and 3 clinical trials, oritavancin was shown to be well-tolerated in addition to being noninferior to vancomycin for the treatment of ABSSSI. The most common side effects experienced were gastrointestinal in nature. CONCLUSIONS: Oritavancin was approved by FDA for the treatment of ABSSSI in August 2014 and is marketed under the trade name Orbactiv. Its reduced dosing and monitoring requirements and efficacy against resistant gram-positive pathogens provide a unique profile that distinguishes it from current options in the treatment of ABSSSI.

Leveraging mobile smart devices to improve interprofessional communications in inpatient practice setting: A literature review.

As mobile smart device use has increased in society, the healthcare community has begun using these devices for communication among professionals in practice settings. The purpose of this review is to describe primary literature which reports on the experiences with interprofessional healthcare communication via mobile smart devices. Based on these findings, this review also addresses how these devices may be utilized to facilitate interprofessional education (IPE) in health professions education programs. The literature search revealed limited assessments of mobile smart device use in clinical practice settings. In available reports, communication with mobile smart devices was perceived as more effective and faster among interdisciplinary members. Notable drawbacks included discrepancies in the urgency labeling of messages, increased interruptions associated with constant accessibility to team members, and professionalism breakdowns. Recently developed interprofessional competencies include an emphasis on ensuring that health profession students can effectively communicate on interprofessional teams. With the increasing reliance on mobile smart devices in the absence of robust benefit and risk assessments on their use in clinical practice settings, use of these devices may be leveraged to facilitate IPE activities in health education professions programs while simultaneously educating students on their proper use in patient care settings.

Daptomycin use in pediatric patients.

PURPOSE: Currently available evidence on the use of daptomycin in pediatric patients is reviewed and evaluated. SUMMARY: Although guidelines on the treatment of methicillin-resistant Staphylococcus aureus infections recommend daptomycin for use in pediatric patients, that recommendation is primarily based on expert opinion. A literature search for articles on pediatric daptomycin use identified three pharmacokinetic studies, three case reports, and one retrospective review. The limited body of published evidence indicates that pediatric patients may require higher daptomycin doses than adult patients in order to attain therapeutic serum concentrations. Pharmacokinetic studies in pediatric patients demonstrated faster daptomycin clearance (CL) and a decreased area under the concentration-time curve (AUC) relative to values reported in adults. Daptomycin appears to have a shorter half-life in patients 2-6 years of age relative to those 12-17 years of age. A retrospective review of 16 cases in which pediatric patients were treated with daptomycin for invasive gram-positive infections indicated positive outcomes after the addition of daptomycin to standard therapy. Overall, daptomycin appears to be well tolerated in pediatric patients. CONCLUSION: Due to the limited nature of the available literature, use of daptomycin in pediatric patients should be limited to situations in which other options are not viable due to toxicity, local susceptibility patterns, or likely treatment failure. As a result of faster drug CL and lower AUC values, higher doses may be necessary in pediatric patients to achieve serum concentrations similar to those seen with adult dosing.

A Novel Structured Format for Engaging Pharmacy Students in Bioethics Discussions.

OBJECTIVE: To describe an active, structured ethics/professionalism discussion format developed for an elective course titled Ethics and Professionalism in Pharmacy. DESIGN: The format uses the acronym ETHICS (Evaluate, Teach, Hear, Interview, Concede, Self-reflect). Before class, students evaluated (Evaluate) literature pertaining to ethics/professionalism topics. Class consisted of faculty-led ethics/professionalism lecture (Teach), student-driven, case discussion, and online self-reflection. Guided by Hear, Interview, and Concede, groups addressed cases from stakeholder perspectives (patient, pharmacist, etc.) considering ethical rules and principles. At the end of class, students answered self-reflection questions. Precourse and postcourse surveys evaluated the impact on students' perceptions of ethical and professional tenets. ASSESSMENT: The format allowed students to actively engage in ethics/professionalism discussions, transforming class into an interactive, structured, student-centered session with self-reflection. CONCLUSION: The format allowed application of concepts to controversial situations. Although the format was created for a pharmacy elective, it is adaptable to any teaching situation.

Comparison of human adipose-derived stem cells isolated from subcutaneous, omental, and intrathoracic adipose tissue depots for regenerative applications.

Adipose tissue is an abundant source of multipotent progenitor cells that have shown promise in regenerative medicine. In humans, fat is primarily distributed in the subcutaneous and visceral depots, which have varying biochemical and functional properties. In most studies to date, subcutaneous adipose tissue has been investigated as the adipose-derived stem cell (ASC) source. In this study, we sought to develop a broader understanding of the influence of specific adipose tissue depots on the isolated ASC populations through a systematic comparison of donor-matched abdominal subcutaneous fat and omentum, and donor-matched pericardial adipose tissue and thymic remnant samples. We found depot-dependent and donor-dependent variability in the yield, viability, immunophenotype, clonogenic potential, doubling time, and adipogenic and osteogenic differentiation capacities of the ASC populations. More specifically, ASCs isolated from both intrathoracic depots had a longer average doubling time and a significantly higher proportion of CD34(+) cells at passage 2, as compared with cells isolated from subcutaneous fat or the omentum. Furthermore, ASCs from subcutaneous and pericardial adipose tissue demonstrated enhanced adipogenic differentiation capacity, whereas ASCs isolated from the omentum displayed the highest levels of osteogenic markers in culture. Through cell culture analysis under hypoxic (5% O(2)) conditions, oxygen tension was shown to be a key mediator of colony-forming unit-fibroblast number and osteogenesis for all depots. Overall, our results suggest that depot selection is an important factor to consider when applying ASCs in tissue-specific cell-based regenerative therapies, and also highlight pericardial adipose tissue as a potential new ASC source.

Use of daptomycin to treat infections with methicillin-resistant Staphylococcus aureus isolates having vancomycin minimum inhibitory concentrations of 1.5 to 2 µg/mL.

OBJECTIVE: To evaluate daptomycin use for the treatment of infections with methicillin-resistant Staphylococcus aureus (MRSA) isolates having vancomycin minimum inhibitory concentrations (MICs) of 1.5 to 2 µg/mL. DATA SOURCES: The literature was retrieved through PubMed and EMBASE (January 2006 to August 2013). STUDY SELECTION AND DATA EXTRACTION: English articles were reviewed. Studies that included separate daptomycin data (clinical outcome or in vitro surveillance) for MRSA isolates with vancomycin MICs of 1.5 to 2 µg/mL by any testing methodology were included. DATA SYNTHESIS: Clinical and microbiological outcomes associated with daptomycin used as first-line or subsequent therapy for MRSA infections with vancomycin MICs of 1.5 to 2 µg/mL were reported in 7 retrospective clinical studies; susceptibility information involving such isolates was reported from 12 surveillancestudies. Although not all studies demonstrated outcome differences between daptomycin and comparator treatments (usually vancomycin), when differences were reported, they were in favor of daptomycin. Individual studies found lower 60-day (8% vs 20%, P = .046) and 30-day mortality (3.5% vs 12.9%, P = .047) and increased treatment success with daptomycin (68.6% vs 43.1%, P = .008; 76.9% vs 53.8%, P = .048) in bacteremic patients. The median doses used for treatment of bacteremia were greater than that approved by the FDA for this indication (6 mg/kg/d). CONCLUSIONS: Current published evidence indicates daptomycin may be an acceptable alternative to vancomycin for MRSA infections, especially bacteremia, involving isolates with vancomycin MIC values of 1.5 to 2 µg/mL. Additional evidence is needed to fully elucidate daptomycin utility in this area.

Inhaled aztreonam lysine for cystic fibrosis pulmonary disease-related outcomes.

OBJECTIVE: To evaluate the pharmacology, clinical efficacy, and safety of aztreonam lysine for inhalation (AZLI) for cystic fibrosis (CF)-related signs and symptoms of pulmonary disease. DATA SOURCES: Literature was searched in MEDLINE through PubMed and cross-referenced with EMBASE (1980-June 2012). The key search terms used were aztreonam lysine, nebulized, inhaled, and cystic fibrosis. Bibliographies of selected articles were used to identify additional references. Ongoing trials were identified through a review of Web site trial registries. STUDY SELECTION AND DATA EXTRACTION: Articles were limited to those written in English about studies conducted in humans. Studies included in this review examined both adult and pediatric patients with CF. DATA SYNTHESIS: Aztreonam lysine is an inhaled monocyclic ß-lactam antibiotic approved for use in the CF population. Four completed clinical trials with peer-reviewed published data were reviewed to assess the efficacy and safety of single-course AZLI; a fifth trial assessed the safety and efficacy of repeat courses of AZLI. None of these trials compared AZLI in a head-to-head manner with tobramycin for inhalation. In patients with moderate to severe pulmonary disease, AZLI administration improved forced expiratory volume in 1 second measurements, decreased sputum bacterial Pseudomonas aeruginosa density, and improved symptoms. Adverse effects in clinical trials were generally mild and similar to those with placebo. CONCLUSIONS: AZLI is safe and effective for management of pulmonary-related symptoms in patients with CF who are colonized with P. aeruginosa and have moderate to severe pulmonary disease. Additional trial data comparing AZLI with tobramycin are warranted to further establish the place of AZLI in therapy.

Chronic pain, healthcare utilization, and quality of life following gastrointestinal surgery.

OBJECTIVES: Our aim in this pilot study was to identify potential predictors of chronic post-surgical pain (CPSP) and other outcomes to consider for inclusion in future prospective studies of CPSP following abdominal gastrointestinal surgery. METHODS: We followed 76 surgical patients during this prospective single-centre cohort study. Pain characteristics, health-related quality of life (HRQOL), and healthcare utilization were assessed preoperatively, at six weeks postoperatively, and at six months postoperatively. Statistical analyses included descriptive statistics and repeated measures analysis of variance. RESULTS: Prior to surgery, 42% of patients reported no pain, 18% reported remote pain, and 33% reported pain at the surgical site. Six months after surgery, 29% of patients with preoperative remote pain and 35% of patients with preoperative pain at the surgical site reported CPSP. Pain-related interference declined from the preoperative to postoperative period; however, six months after surgery almost one-third of participants continued to report pain-related interference with mood (28%), sleep (30%), and enjoyment of life (30%). Consistent with studies of other surgical procedures, measures of anxiety and depression were associated with an increased risk of CPSP. During the six months following surgery, 12% of patients visited the Emergency Department, 15% visited non-traditional providers, and 9.2% visited a walk-in clinic for pain. Compared with Canadian norms, HRQOL was poorer in all domains preoperatively, in all domains but mental health six weeks postoperatively, and in most domains six months postoperatively. CONCLUSION: This feasibility study provides a template for future studies of CPSP following gastrointestinal surgery. Results suggest a substantial burden of persistent pain, healthcare utilization, and decreased HRQOL. Larger-scale studies that are similarly designed will serve to identify predictors of CPSP in this surgical population.

Left-sided sigmoid diverticulitis presenting as right-sided thigh abscess.

Acquired diverticular disease of the colon is very common in the North American population. Atypical presentations are usually due to complications and rarely the predominant complaint may be related to an associated fistula. Thigh abscesses due to colocutaneous fistula represent an uncommon complication of sigmoid diverticulitis. In rare cases, a thigh abscess may be the only symptom, but gas in the thigh should raise the index of suspicion for bowel pathology. We report the second known case of a left-sided sigmoid diverticulitis leading to an isolated right thigh abscess with no gastrointestinal symptoms.

Boceprevir: a protease inhibitor for the treatment of chronic hepatitis C.

OBJECTIVE: To review the pharmacology, pharmacokinetics, safety, and efficacy of boceprevir, a novel oral hepatitis C virus (HCV) nonstructural 3 (NS3) protease inhibitor for the treatment of chronic HCV infection, specifically, genotype 1. DATA SOURCES: A literature search was conducted through MEDLINE and EMBASE (1966-May 2011) using the terms boceprevir and SCH 503034. Data from the package insert, abstracts obtained from conferences, and unpublished Phase 2-3 clinical trials, obtained through clinicaltrials.gov, were also reviewed. STUDY SELECTION AND DATA EXTRACTION: All English-language articles identified from the data sources were evaluated. References from selected articles were used to identify other pertinent citations. Article selection focused on pharmacology, clinical trials, safety analyses, and resistance. Preference was given to human data. DATA SYNTHESIS: Boceprevir is an oral protease inhibitor that binds to the NS3 protein of HCV, ultimately inhibiting viral intracellular replication. Boceprevir displays linear pharmacokinetics and is rapidly absorbed upon oral administration. In clinical studies of treatment-naïve and treatment-experienced patients, boceprevir, in combination with standard of care (pegylated interferon [Peg-IFN]-α-2b with or without ribavirin) achieved greater sustained viral response (SVR) rates compared to standard of care. Safety analyses showed an increased incidence of adverse effects when boceprevir was used with Peg-IFN-α-2b and ribavirin. The most common adverse events reported include fatigue, headache, nausea, dysguesia, and anemia; the incidence of the latter 2 adverse effects may be increased if boceprevir is added to standard therapy. Additional Phase 2 and 3 studies are currently enrolling participants. CONCLUSIONS: Boceprevir should be used in combination with Peg-IFN-α-2b and ribavirin in the treatment of chronic HCV genotype 1 infection. The improved response rates achieved with that combination will make boceprevir a viable option compared with other developing and approved NS3 protease inhibitors for treatment-naïve and treatment-experienced nonresponders/relapsers. Additional data are needed to clarify the potential for resistance and drug interactions.

Tigecycline for the treatment of severe Clostridium difficile infection.

OBJECTIVE: To evaluate the evidence for the use of tigecycline in the treatment of Clostridium difficile infection (CDI). DATA SOURCES: Searches were performed (2004 to June 2011), using the EMBASE and MEDLINE databases, with the terms tigecycline, Tygacil, Clostridium difficile, C. difficile, Clostridium difficile infection, and CDI. STUDY SELECTION: Six case reports that described the use of tigecycline for treatment of CDI were included for review. No clinical trials were identified. DATA SYNTHESIS: In all case reports except 1, tigecycline (alone or in combination with other CDI therapies) was used for the treatment of CDI that was refractory to metronidazole and/or vancomycin. In 6 of the cases, treatment success was reported following initiation of tigecycline therapy; 1 patient died following a complicated hospitalization. The treatment duration with tigecycline was 2-4 weeks. In the cases with successful outcomes, symptoms began to improve within 1 week. None of these patients experienced recurrence during follow-up of various lengths. In vitro studies demonstrated a 90% minimum inhibitory concentration range for tigecycline of 0.016-0.25 mg/L for all C. difficile isolates. Tigecycline exhibited good fecal penetration because of primary biliary excretion of unchanged drug. Up to 59% of the dose is recovered in feces following administration over 4 days in healthy volunteers. CONCLUSIONS: Case reports have suggested that tigecycline may be successful for treatment of severe or severe complicated CDI, when prior therapy has failed. Data demonstrating tigecycline use as initial therapy for CDI are limited; therefore, this option should be reserved for patients in whom other therapeutic options, including metronidazole and vancomycin, have failed. A randomized controlled trial is needed to assess the safety and efficacy of tigecycline in this patient population and better define the drug's role in the treatment of CDI.

Vigabatrin for infantile spasms.

Infantile spasms describe a pediatric epilepsy syndrome characterized by frequent clusters of brief symmetric muscle contractions; the condition is often associated with developmental delay. When infantile spasms are accompanied by hypsarrhythmia on electroencephalogram, the condition is labeled West syndrome. The mainstay of treatment for infantile spasms is adrenocorticotropic hormone; however, vigabatrin, a vinyl derivative of γ-aminobutyric acid, has been used for the treatment of infantile spasms in Europe since 1989. In 2009, vigabatrin was approved by the United States Food and Drug Adminstration (FDA) for use as monotherapy in the treatment of infantile spasms in patients aged 1 month-2 years when the benefits of treatment outweigh the risks. Results from numerous trials examining the role of vigabatrin in infantile spasms have been published; many of these trials were small, open-label, or noncontrolled. Although clinical trials have provided some insight into the utility of vigabatrin for the treatment of infantile spasms, these studies have notable limitations. In addition, vigabatrin is associated with a black-box warning that describes the potential for permanent bilateral concentric visual field defects. Currently, vigabatrin is available through a manufacturer-sponsored program in accordance with its FDA-approved Risk Evaluation and Mitigation Strategy. Although several guidelines recommend vigabatrin as a first-line therapy for infantile spasms, specifically infantile spasms related to tuberous sclerosis, it is still unclear whether vigabatrin should supersede hormone therapy as first-line therapy. Further research comparing the two therapies is needed.

An electronic NAPLEX review program for longitudinal assessment of pharmacy students' knowledge.

OBJECTIVES: To track pharmacy student knowledge over time using a proprietary software program in an accelerated program for curricular assessment. METHODS: All students were required to complete a computerized comprehensive diagnostic examination 3 times during the doctor of pharmacy (PharmD) program: at the beginning of the second year, and near the end of the second and third years. The examination was comprised of 100 questions in 3 content areas: pharmacotherapy, preparation and dispensing of medications, and providing health care information. Within-subject differences in mean area and total percent scores were compared. RESULTS: Based on 123 students' data, mean scores for pharmacotherapy and total percent scores for examination 1 were significantly different from examinations 2 and 3. CONCLUSION: The computer-based comprehensive diagnostic examination shows promise for use as a component of a comprehensive assessment plan.

Apricitabine: a nucleoside reverse transcriptase inhibitor for HIV infection.

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of apricitabine, a nucleoside reverse transcriptase inhibitor that is currently under investigation and has fast-track approval status with the Food and Drug Administration. DATA SOURCES: A literature search was conducted using PubMed (1966-June 2009) to retrieve relevant material using the search terms apricitabine, SPD754, and AVX754. References from selected articles were evaluated to identify other pertinent trials. Information was also obtained from the manufacturer. STUDY SELECTION AND DATA EXTRACTION: All English-language in vitro and in vivo studies and abstracts evaluating apricitabine were reviewed and considered for inclusion. Preference was given to human data. DATA SYNTHESIS: Apricitabine is a prodrug that is phosphorylated to its active triphosphate form intracellularly, which ultimately results in chain termination and inhibition of reverse transcription. Apricitabine is administered orally, displays linear pharmacokinetics, and is renally excreted with minimal to no hepatic metabolism. It has demonstrated antiretroviral activity against drug-resistant strains both in vitro and in vivo. In clinical studies, in both antiretroviral-naïve and treatment-experienced patients, apricitabine achieved the primary endpoint of significant reductions in plasma viral load versus comparator. Further Phase 2 and 3 studies are currently enrolling. Safety analysis indicates that apricitabine is well tolerated and has a low potential for causing mitochondrial damage. The most common adverse events reported include headache and rhinitis. Development of resistance or further gene mutations has not been shown in clinical studies to date. CONCLUSIONS: Although the role of apricitabine in the treatment of HIV-1 infection has yet to be established, its activity against resistant HIV-1 strains and its tolerability profile will likely make it a viable second-line treatment option in patients who have failed regimens containing lamivudine or emtricitabine.

Excretion of antimicrobials used to treat methicillin-resistant Staphylococcus aureus infections during lactation: safety in breastfeeding infants.

Community-acquired strains of methicillin-resistant Staphylococcus aureus (MRSA) have become a common cause of skin and soft tissue infections in the United States. These infections sometimes require treatment with antibiotics, and with the increasing resistance of pathogens to these agents, choosing the appropriate drug can be difficult. In lactating women who develop these infections, selecting an antibiotic is even more challenging, as clinicians need to be aware of risks to the infant from the drug excreted during lactation. To our knowledge, no review has addressed the safety of antibiotics in breastfeeding infants when the drugs are used to treat maternal skin and soft tissue infections from MRSA. Thus, we performed a literature search of the PubMed-MEDLINE and EMBASE databases (1974-March 2009), reviewed reference citations from identified publications, researched antibiotic prescribing information, and corresponded with drug manufacturers. Case reports, case series, and both in vivo and in vitro clinical trials were evaluated for the following antibiotics: clindamycin, daptomycin, linezolid, quinupristin-dalfopristin, rifampin, tetracycline, doxycycline, minocycline, tigecycline, trimethoprim-sulfamethoxazole, and vancomycin. Information for the newer antibiotics (linezolid, quinupristin-dalfopristin, tigecycline, and daptomycin) was limited. Despite heterogeneity in the data for the older antibiotics (clindamycin, rifampin, tetracyclines, trimethoprim-sulfamethoxazole, and vancomycin), all appear to be relatively safe in the minimal quantities nursing infants ingest through breast milk. Although the risk to infants seems to be relatively low for most of the agents we explored, the paucity of data indicates a need for close monitoring of breastfed infants whose mothers are receiving an antibiotic for an MRSA skin and soft tissue infection.