A reflective teaching challenge to motivate educational innovation.

OBJECTIVE: To describe a teaching challenge intended to increase faculty use of evidence-based and student-centered instructional strategies in the demanding school of pharmacy context with technology-savvy students. DESIGN: A teaching challenge was created that required faculty members to incorporate a "new-to-you" innovative teaching method in a class, course, or experiential activity. The method was linked to at least 1 of 7 evidence-based principles for effective teaching. Faculty members were exposed to colleagues' teaching strategies via brief voluntary presentations at department meetings. ASSESSMENT: A post-challenge survey provided assessment data about the challenge. Responses to a baseline survey provided additional information about what faculty members were already doing (52% response rate). Eighty-one percent of faculty respondents completed the challenge. A wide array of new strategies (13 categories such as flipped classrooms and social media) was implemented and 75% included the use of technology. Nearly all respondents (96%) thought that participation in the challenge was worth the effort and planned to participate again the following year. All faculty members intended to continue using their new strategy and 56% planned additional modifications with future implementations. The challenge demonstrated how multiple goals of curricular improvement, faculty development, and student-centered instruction could be achieved together. CONCLUSION: The teaching challenge motivated most of the faculty members to try something new to them. Links between evidence-based principles and day-to-day activities were strengthened. The new-to-you design placed the challenge within reach of faculty members regardless of their background, subject, or experience.

Follow-up assessment of a faculty peer observation and evaluation program.

OBJECTIVE: To assess a previously described peer observation and evaluation program 2 years after implementation. METHODS: An pre-implementation survey assessed faculty needs and attitudes related to peer evaluation. Two years after implementation, the survey was repeated and additional questions asked regarding adherence to peer observation and evaluation policies and procedures, feedback received, and impact on teaching. RESULTS: Faculty attitudes towards peer evaluation stayed the same or improved post-implementation. Adherence to the initial 3 steps of the process was high (100%, 100%, and 94%, respectively); however, step 4, which required a final discussion after student assessments were finished, was completed by only 47% of the respondents. All faculty members reported receiving a balance of positive and constructive feedback; 78% agreed that peer observation and evaluation gave them concrete suggestions for improving their teaching; and 89% felt that the benefits of peer observation and evaluation outweighed the effort of participating. CONCLUSIONS: Faculty members adhered to the policies and procedures of peer observation and evaluation and found peer feedback was beneficial.

Fidaxomicin: the newest addition to the armamentarium against Clostridium difficile infections.

BACKGROUND: Fidaxomicin, a macrolide antibiotic, was the first medication for the management of Clostridium difficile infections (CDI) to be approved by the US Food and Drug Administration in more than 20 years. OBJECTIVE: This article reviews published literature on fidaxomicin for management of CDI, including its chemistry, spectrum of activity, pharmacokinetic properties, pharmacodynamics, therapeutic efficacy, adverse events, dosing, administration, and pharmacoeconomic considerations. METHODS: Pertinent English-language literature was reviewed through searches of MEDLINE, EMBASE, and BIOSIS from 1975 through September 2011. Reference lists of identified publications and published abstracts from the Interscience Conference on Antimicrobial Agents and Chemotherapy meetings were also reviewed. Search terms included, but were not limited to, fidaxomicin, difimicin, lipiarmycin, tiacumicin B, OPT-80, Clostridium spp, and diarrhea. RESULTS: A total of 79 publications were identified and 10 were excluded; 6 review articles and 4 abstracts that were later published as articles. Fidaxomicin's in vitro profile is favorable compared with oral metronidazole and vancomycin, with minimum inhibitory concentrations against C difficile that are 2 dilutions lower. From the 2 published Phase III trials, fidaxomicin was deemed to be noninferior in the treatment of mild to moderate CDI compared with oral vancomycin. Recurrence rates for all strains of CDI were lower with fidaxomicin than vancomycin. Adverse events associated with fidaxomicin were similar to placebo, with nausea and vomiting being the most common. Although no pharmacoeconomic studies have compared fidaxomicin with metronidazole or vancomycin, the current price exceeds $2500 (US) per treatment course. CONCLUSIONS: Reports suggest that fidaxomicin is noninferior to oral vancomycin in the treatment of mild or moderate CDI, although no published comparisons with metronidazole exist to date. Additionally, fidaxomicin improved outcomes compared with oral vancomycin in terms of rates of relapse and recurrent CDI, and in patients who might require concomitant antibiotics. Prospective, randomized studies comparing fidaxomicin with metronidazole in the treatment of mild or moderate CDI, as well as against vancomycin for severe CDI, should be undertaken to clarify the exact role of fidaxomicin in clinical practice.

Urinary tract infections in the elderly population.

BACKGROUND: Urinary tract infections (UTIs) are a common problem in the elderly population. The spectrum of disease varies from a relatively benign cystitis to potentially life-threatening pyelonephritis. OBJECTIVE: This review covers the management of asymptomatic bacteriuria, acute uncomplicated cystitis, acute uncomplicated pyelonephritis, antibiotic resistance, catheter-associated bacteriuria/symptomatic UTIs, and antibiotic prophylaxis for recurrent infections in elderly men and women. METHODS: Literature was obtained from English-language searches of MEDLINE (1966-April 2011), Cochrane Library, BIOSIS (1993-April 2011), and EMBASE (1970-April 2011). Further publications were identified from citations of resulting articles. Search terms included, but were not limited to, urinary tract infections, asymptomatic bacteriuria, acute uncomplicated cystitis, acute uncomplicated pyelonephritis, antibiotic resistance, catheter associated urinary tract infections, recurrent urinary tract infections, and elderly. RESULTS: The prevalence of UTIs in elderly women depends on the location in which these women are living. For elderly women living in the community, UTIs compromise the second most common infection, whereas in residents of long-term care facilities (LTCFs) and hospitalized subjects, it is the number one cause of infection. The spectrum of patient presentation varies from classic signs and symptoms in the independent elderly population to atypical presentations, including increased lethargy, delirium, blunted fever response, and anorexia. Although there are few guidelines specifically directed toward the management of UTIs in the elderly population, therapy generally mirrors the recommendations for the younger adult age groups. When choosing a treatment regimen, special attention must be given to the severity of illness, living conditions, existing comorbidities, presence of external devices, local antibiotic resistance patterns, and the ability of the patient to comply with therapy. CONCLUSIONS: Improved guidelines for the diagnosis and management of UTIs in the elderly population are needed. Better techniques to evaluate and prevent catheter-associated bacteriuria and UTIs await improved diagnostic modalities and catheter technologies. Alternative methods for prophylaxis of patients who suffer from recurrent infections must be found while minimizing the risk of developing or propagating antibiotic resistance.

Doripenem monohydrate, a broad-spectrum carbapenem antibiotic.

BACKGROUND: Doripenem monohydrate, a broad-spectrum carbapenem antibiotic, has been approved by the US Food and Drug Administration for the treatment of complicated intra-abdominal infections (cIAIs) and complicated urinary tract infections (cUTIs). OBJECTIVE: This article reviews available information on doripenem in the management of patients with complicated bacterial infections, including its chemistry, spectrum of activity, resistance mechanisms, pharmacokinetics, pharmacodynamics, drug interactions, therapeutic efficacy, tolerability, and dosing and administration. Also discussed are pharmacoeconomic considerations associated with doripenem. METHODS: Pertinent English-language literature was identified from searches of MEDLINE (1996-October 2008) and BIOSIS (1993-October 2008). Search terms included, but were not limited to, doripenem, S-4661, spectrum of activity, resistance, pharmacology, pharmacokinetics, pharmacodynamics, adverse events, and therapeutic use. Additional publications were found by searching the reference lists of identified articles and reviewing abstracts from meetings of the Interscience Conference on Antimicrobial Agents and Chemotherapy (2003-2007). RESULTS: Doripenem is a parenteral carbapenem antibiotic with in vitro activity against gram-positive, gram-negative, and anaerobic organisms. It is stable against a wide variety of beta-lactamases, including extended-spectrum and AmpC beta-lactamases; it is, however, inactivated by organisms that produce class A enzymes, KPC enzymes, class B metallo-beta-lactamases, and class D enzymes. Doripenem is eliminated primarily in the urine (68%-80% unchanged). It should be used cautiously in patients receiving valproic acid, as combined use may lead to a precipitous decline in serum concentrations of valproic acid. A large Phase III study in the treatment of cIAIs found doripenem noninferior to meropenem (clinical cure rates, 83.9% and 85.9%, respectively; difference, -2.1; 95% CI, -9.8 to 5.6). A Phase III study in the treatment of cIAIs, including pyelonephritis, found doripenem non-inferior to levofloxacin (clinical cure rates, 95.1% and 90.2%, respectively; 95% CI, 0.2 to 9.6). With respect to the treatment of nosocomial pneumonia, one Phase III study found doripenem noninferior to imipenem (clinical cure rates, 68.3% and 64.8%, respectively; difference, 3.5%; 95% CI, -9.1 to 16.1), and another found it noninferior to piperacillin/tazobactam (clinical cure rates, 81.3% and 79.8%, respectively; difference, 1.5%; 95% CI, -9.1 to 12.1). Adverse events with doripenem were similar to those of other antibiotics with which it has been compared. Adverse events in clinical trials of doripenem have included anaphylaxis and rash (l%-5%), gastrointestinal effects (25%-32%, including nausea [1.1%-12.0%], diarrhea [1.9%-11.0%], and vomiting [1.5%-6.6%]), and central nervous system effects (headache [2.1%-16.0%], insomnia [3.7%], anxiety [2.9%], and, rarely, seizures). CONCLUSIONS: In Phase III studies, doripenem was noninferior to meropenem in the treatment of cIAIs; noninferior to levofloxacin in the treatment of cUTIs; and noninferior to imipenem and piperacillin/tazobactam in the treatment of nosocomial pneumonia. As with all new antibiotics, because of the risk of selecting for resistant organisms, use of doripenem should be reserved for infections in which a multidrug-resistant gram-negative organism, polymicrobial infection, or Pseudomonas aeruginosa is suspected.

Development of a peer teaching-assessment program and a peer observation and evaluation tool.

OBJECTIVES: To develop a formalized, comprehensive, peer-driven teaching assessment program and a valid and reliable assessment tool. METHODS: A volunteer taskforce was formed and a peer-assessment program was developed using a multistep, sequential approach and the Peer Observation and Evaluation Tool (POET). A pilot study was conducted to evaluate the efficiency and practicality of the process and to establish interrater reliability of the tool. Intra-class correlation coefficients (ICC) were calculated. RESULTS: ICCs for 8 separate lectures evaluated by 2-3 observers ranged from 0.66 to 0.97, indicating good interrater reliability of the tool. CONCLUSION: Our peer assessment program for large classroom teaching, which includes a valid and reliable evaluation tool, is comprehensive, feasible, and can be adopted by other schools of pharmacy.

Telbivudine for the management of chronic hepatitis B virus infection.

BACKGROUND: Telbivudine (LdT) is an L-nucleoside that is structurally related to lamivudine. It is highly selective for hepatitis B virus (HBV) and inhibits viral DNA synthesis. LdT was approved by the US Food and Drug Administration on October 25, 2006, for the treatment of chronic HBV infection in adults who have active viral replication and either elevations in liver transaminases or signs of active liver disease on histologic examination. OBJECTIVE: This article reviews the pharmacology, pharmacokinetics, and therapeutic efficacy of LdT. Potential drug interactions and adverse events associated with the use of LdT are also reviewed. METHODS: Relevant publications were identified from searches of MEDLINE (1996-June 2007), the Cochrane Library, and BIOSIS (1993-June 2007). Search terms included, but were not limited to, telbivudine, beta-L-thymidine, LdT, pharmacology, pharmacokinetics, adverse events, resistance, drug interactions, hepatitis B, and therapeutic use. Additional publications were identified from the reference lists of the identified papers, meeting abstracts, and correspondence with the manufacturer of LdT. RESULTS: After 52 weeks of therapy in the Phase III GLOBE study, HBV resistance (breakthrough and resistance mutations) to LdT occurred in 3% of patients who were hepatitis B e antigen (HBeAg) positive and 2% of patients who were HBeAg negative. After 104 weeks of therapy, 17.8% to 21.6% of HBeAg-positive and 7.3% to 8.6% of HBeAg-negative LdT-treated patients had a rebound in HBV DNA associated with breakthrough and resistance mutations. After 24 weeks of treatment, the risk of resistance was greater in patients with HBV DNA titers >3 log(10) copies/mL than in those with lower numbers of copies. LdT is not active against lamivudine-resistant HBV. The proportion of HBeAg-positive patients with undetectable HBV DNA (by polymerase chain reaction assay) after 104 weeks of therapy in the GLOBE study was significantly greater with LdT compared with lamivudine (56% vs 39%, respectively; P < 0.05). After 104 weeks of therapy, the corresponding proportions of HBeAg-negative patients with undetectable HBV DNA were 82% and 57% (P < 0.05). Patients who failed lamivudine therapy in the GLOBE study showed cross-resistance to LdT. The most common adverse events associated with LdT are upper respiratory tract infection (14%-17%), fatigue and malaise (12%-14%), nasopharyngitis (11%-15%), headache (11%-12%), and abdominal pain (6%-12%). Grade 3/4 adverse events included elevations in serum creatine kinase, which were more common in patients receiving LdT than in those receiving lamivudine (9% vs 3%, respectively). Elevations in creatine kinase are typically asymptomatic; however, myopathy has been reported in 3 of 680 patients receiving LdT. CONCLUSIONS: LdT joins the increasing number of antiviral agents for the management of chronic HBV infection. Questions concerning the optimal length of therapy and long-term efficacy await the results of on-going clinical trials. Concerns about increasing resistance over time may relegate LdT to second-line status in the management of chronic HBV infection. The role of LdT in combination therapy is under investigation.

Entecavir for the treatment of chronic hepatitis B virus infection.

OBJECTIVE: This article reviews the pharmacology/pharmacokinetics and therapeutic efficacy of entecavir, which was approved on March 29, 2005, for the management of adult patients with chronic hepatitis B virus (HBV) infection who have active viral replication and/or elevations in liver transaminases or signs of active liver disease on histologic examination. Potential drug interactions and adverse events associated with the use of entecavir are also reviewed. METHODS: Relevant literature was identified through searches of MEDLINE (1996-July 2005) and BIOSIS (1993-July 2005). Search terms included, but were not limited to, entecavir, BMS-200475, hepatitis B, pharmacology, pharmacokinetics, adverse events, and therapeutic use. Further publications were identified from the reference lists of the identified articles and through correspondence with the manufacturer of entecavir. RESULTS: Entecavir is highly selective for the HBV and inhibits all 3 steps of viral replication. Results of early studies indicated a 6% resistance potential after 48 weeks of therapy, although the potential may be higher in patients who harbor lamivudine-resistant mutants. The approved dosage in treatment-naive patients is 0.5 mg/d p.o., administered on an empty stomach; in patients who have failed lamivudine therapy or are known to harbor lamivudine-resistant mutants, the approved dosage is 1.0 mg/d p.o.. The oral tablet and solution can be used interchangeably. Entecavir is well absorbed orally, achieving a dose-related Cmax between 0.6 and 1.5 hours after administration. It is metabolized to a small extent and is not a substrate for the cytochrome P450 enzyme system. The mean elimination t(1/2) ranges from 77 to 149 hours in patients with normal kidney function. Entecavir is eliminated primarily in the urine via glomerular filtration and tubular secretion (62%-73%). No dose adjustment appears to be necessary in patients with moderate to severe liver disease alone. The potential for drug interactions with entecavir appears to be minimal, although medications that inhibit tubular secretion of drugs (eg, probenecid) may be expected to prolong serum concentrations of entecavir. One of the Phase III studies of entecavir found statistically significant benefits compared with lamivudine in terms of improvements in liver histology after 48 weeks of therapy (72% vs 62%, respectively; P<0.009), the proportions of patients with undetectable HBV DNA titers on branched DNA signal amplification assay after 48 weeks of therapy (91% vs 65%; P<0.001), and the proportion with undetectable HBV DNA on polymerase chain reaction (PCR) assay after 48 weeks of therapy (69% vs 38%; P<0.001). In another Phase III study, patients who had failed to respond to lamivudine therapy responded to entecavir: after 48 weeks of therapy, significant differences between entecavir and lamivudine were seen in histologic improvement (55% vs 28%; P<0.001) and the proportion of patients with undetectable HBV DNA on PCR assay (21% vs 1%; P<0.001). Adverse events associated with entecavir therapy were similar in character, severity, and incidence to those associated with placebo or lamivudine therapy. The most common adverse events in clinical trials of entecavir were headache (17%-23% of patients), upper respiratory tract infection (18%-20%), cough (12%-15%), nasopharyngitis (9%-14%), fatigue (10%-13%), dizziness (9%), upper abdominal pain (9%-10%), and nausea (6%-8%). CONCLUSIONS: Entecavir is a new antiviral agent for the management of chronic HBV infection. Questions concerning the ideal length of therapy, long-term efficacy, and resistance rates over time await the results of ongoing clinical trials.

Peginterferon alfa-2a: a review of approved and investigational uses.

BACKGROUND: In October 2002, the US Food and Drug Administration approved peginterferon alfa-2a for the management of chronic hepatitis C virus (HCV) infection. The addition of polyethylene glycol (PEG) moiety to the interferon (IFN) molecule results in a product with altered pharmacokinetic properties. OBJECTIVE: The aim of this article is to review the pharmacology, medications interactions, adverse events (AEs), and approved or investigational uses of PEG-IFN alfa-2a for viral hepatitis and oncologic conditions. METHODS: Relevant articles were identified through searches of MEDLINE (1980-July 2003) and EMBASE (1980-July 2003). Search terms included, but were not limited to, peginterferon alfa-2a, pharmacokinetics, pharmacology, pharmacodynamics, and therapeutic use, as well as terms for specific disease states and AEs. Further publications were identified from citations of resulting papers. RESULTS: Pegylation of IFN alfa-2a results in major changes in the pharmacokinetics of the product. Absorption is prolonged and serum concentrations are sustained over the dosing regimen. PEG-IFN alfa-2a has been shown to be more effective with or without ribavirin (RBV), in the management of treatment-naive patients with chronic HCV infection, than unmodified IFN alfa-2a with or without RBV. Results in other disease states are still preliminary. AEs are similar, in incidence and severity, to those occurring with unmodified IFN. They include earlier hematologic symptoms and fewer influenza-like symptoms. Drug-drug interactions are the same as those occurring with the unmodified IFN product. CONCLUSIONS: The pharmacokinetic profile of IFN alfa-2a is improved by pegylation, which enables less frequent administration and results in improved efficacy with a similar side-effect profile. Combination of PEG-IFN alfa-2a with RBV is associated with a greater chance of achieving a sustained virologic response in treatment-naive patients with chronic HCV, compared with unmodified IFN alfa-2a/RBV combinations. Documentation of efficacy in other conditions awaits results of controlled clinical trials.

Thalidomide: a review of approved and investigational uses.

BACKGROUND: Thalidomide is best known as a major teratogen that caused birth defects in up to 12,000 children in the 1960s. More recently, this agent has been approved by the US Food and Drug Administration for the treatment of erythema nodosum leprosum (ENL) through a restricted-use program. Its immunomodulatory, anti-inflammatory, and antiangiogenic properties are currently under study in a number of clinical conditions. OBJECTIVE: This article reviews the pharmacology of thalidomide; its approved and off-label uses in dermatologic, oncologic, and gastrointestinal conditions; and adverse events associated with its use. METHODS: Relevant articles were identified through searches of MEDLINE (1966-June 2002), International Pharmaceutical Abstracts (1970-June 2002), and EMBASE (1990-June 2002). Search terms included but were not limited to thalidomide, pharmacokinetics, pharmacology, therapeutic use, and teratogenicity, as well as terms for specific disease states and adverse events. Further publications were identified from the reference lists of the reviewed articles. Abstracts of recent symposia were obtained from the American Society of Clinical Oncology Web site. RESULTS: Thalidomide is thought to exert its therapeutic effect through the modulation of cytokines, particularly tumor necrosis factor-alpha. In addition to its approved indication for ENL, thalidomide has been studied in various other conditions, including graft-versus-host disease, discoid lupus erythematosus, sarcoidosis, relapsed/refractory multiple myeloma, Waldenstrom's macroglobulinemia, myelodysplastic syndromes, acute myeloid leukemia, myelofibrosis with myeloid metaplasia, renal cell carcinoma, malignant gliomas, prostate cancer, Kaposi's sarcoma, colorectal carcinoma, oral aphthous ulcers, Behçet's disease, Crohn's disease, and HIV/AIDS-associated wasting. Adverse events most frequently associated with its use include somnolence, constipation, rash, peripheral neuropathy, and thromboembolism. CONCLUSIONS: Use of thalidomide is limited by toxicity, limited efficacy data, and restricted access. Evidence of its efficacy in conditions other than ENL awaits the results of controlled clinical trials.