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Telaprevir is a hepatitis C NS3/4A protease inhibitor approved by the US Food and Drug Administration as part of combination therapy for the management of chronic hepatitis C virus (HCV) genotype 1 infection. The article reviews published literature on telaprevir, including its chemistry, mechanism of action, resistance, pharmacodynamic and pharmacokinetic properties, drug interactions, therapeutic efficacy, HIV/HCV coinfection, pharmacogenomics, adverse events, pharmacoeconomics, and dosing and administration. English-language literature was included. Searches of MEDLINE and BIOSIS databases from 1975 through January 2012 were performed. Emphasis was placed on reference citations involving clinical trials, randomized controlled trials, and research in humans. Additional publications were found by searching the reference lists of identified articles and reviewing abstracts from recent scientific meetings. Search terms included, but were not limited to, telaprevir, VX-950, hepatitis C virus genotype 1, resistance, pharmacology, pharmacokinetics, pharmacodynamics, drug interactions, pharmacogenomics, adverse events, and therapeutic use. Review of the databases revealed 471 publications/abstracts on this subject. Of these, 85 were chosen based on the review criteria. Two Phase III studies investigated the efficacy and tolerability of telaprevir administered for 12 weeks (T12) when used with peginterferon alfa and ribavirin (PR) in treatment-naive subjects. The ADVANCE study reported that patients who had an extended rapid virologic response (eRVR; an undetectable HCV RNA level at both 4 and 12 weeks of treatment) with triple therapy could be treated with PR for a total of 24 weeks (T12PR24 group) versus standard PR treatment for 48 weeks (PR48 group [control]). The proportions of patients who achieved sustained virologic response (SVR; undetectable HCV RNA concentration at 24 weeks after the completion of therapy) in the T12PR24 and PR48 groups were 89% and 44%, respectively. The ILLUMINATE study reported T12PR24 was noninferior to T12PR48 in patients with an eRVR to combination therapy. In the REALIZE study, patients with a history of relapse responded well to T12PR48 compared with PR48 (SVR, 83% vs 24%). Telaprevir is a substrate/inhibitor of cytochrome P450 (CYP3A4) and a substrate/inhibitor of P-glycoprotein and poses an important risk for drug interactions. Adverse drug events (ADEs) reported most commonly with triple therapy compared with the T or PR regimen alone were rash, pruritus, nausea, diarrhea, and anemia. The serious AEs most commonly reported during T + PR therapy were anemia, rash, and pruritus. Two reports concluded that T combined with PR was not cost-effective due to the high cost of telaprevir. One study reported that the combination of T + PR would be cost-effective if the treatment rate of HCV genotype 1 infected patients reached 50%. Including telaprevir as part of triple therapy for the management of chronic HCV genotype 1 infection significantly increases the likelihood of achieving an SVR over standard dual drug therapy (PR) in both treatment-naive and -experienced patients. However, due to the high cost, the use of triple therapy with telaprevir will likely be limited to patient groups known to respond poorly to dual therapy.

The use of tablet computers and other touch screen technology within the healthcare system has rapidly expanded. It has been reported that these devices can harbor pathogens in hospitals; however, much less is known about what pathogens they can harbor when used outside the hospital environment compared to hospital practice. Thirty iPads belonging to faculty with a variety of practice settings were sampled to determine the presence and quantity of clinically-relevant organisms. Flocked nylon swabs and neutralizer solution were used to sample the surface of each iPad. Samples were then plated on a variety of selective agars for presence and quantity of selected pathogens. In addition, faculty members were surveyed to classify the physical location of their practice settings and usage patterns. Continuous variables were compared via an unpaired Student's t test with two-tailed distribution; categorical variables were compared with the Fisher's exact test. Of the iPads sampled, 16 belonged to faculty practicing within a hospital and 14 belonged to a faculty member practicing outside a hospital. More faculty within the hospital group used their iPads at their practice sites (78.6% vs. 31.3%; p = 0.014) and within patient care areas (71.4% vs. 18.8%; p = 0.009) than the non-hospital group. There were no differences in the presence, absence, or quantity of, any of the pathogens selectively isolated between groups. Problematic nosocomial pathogens such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and P. aeruginosa were isolated from both hospital and non-hospital faculty iPads. Gram positive and Gram negative organisms were recovered from the surfaces of iPads regardless of practice setting; these included problematic multidrug-resistant pathogens like MRSA, VRE, and Pseudomonas aeruginosa. Healthcare personnel in all settings should be aware of the potential for tablet computers to serve as a nidus for microorganism transmission.

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. 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. 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. 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. 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.

BackgroundDirect oral anticoagulants (DOACs) are the preferred treatment for venous thromboembolism (VTE). However, DOAC use in patients with a BMI greater than 40 kg/m2 has not been well studied despite the growing prevalence of obesity, and current literature is often underpowered.MethodsThis multicenter, retrospective, observational study evaluated patients 18 years and older who received DOACs for acute VTE treatment. Patients receiving DOACs for recurrent VTE or for failure of another agent were excluded. The primary efficacy outcome was recurrent VTE and the primary safety outcome was major bleeding within 12 months (or one month after stopping anticoagulation therapy). A propensity score analysis was performed to balance patient characteristics and evaluate the primary endpoints by BMI group. Time-to-event outcomes were analyzed using weighted Kaplan-Meier curves.ResultsThere were 165 patients with a BMI of at least 40 kg/m2 and 320 patients with a BMI less than 40 kg/m2. The majority received apixaban (373, 77%). Recurrent VTE occurred in 5 (3.0%) and 13 (4.1%) of patients in the higher and lower BMI groups, respectively (adjusted OR: 0.66; 95% CI: 0.16–2.69). Major bleeding occurred in 5 (3.0%) and 15 (4.7%) of patients in the higher and lower BMI groups, respectively (adjusted OR: 1.19; 95% CI: 0.36–3.92).ConclusionThere was no significant difference in VTE recurrence or major bleeding related to BMI among patients treated with DOACs. This study showed that DOACs may be a safe and effective VTE treatment option in patients with obesity.Key pointsData supporting the use of direct oral anticoagulants (DOACs) for the treatment of venous thromboembolism (VTE) in patients with obesity are limited.This multicenter analysis aimed to evaluate the effectiveness and safety of DOACs in patients with and without obesity.The majority of patients received apixaban.VTE recurrence and rates of major bleeding were not different between patients with a BMI of at least 40 kg/m2 compared to a BMI less than 40 kg/m2.This study adds to the growing body of evidence supporting the use of DOACs, particularly apixaban, in patients with obesity, although future prospective trials and additional data in patients at extremes of body weight will be useful.

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 β-lactamases, including extended-spectrum and AmpC β-lactamases; it is, however, inactivated by organisms that produce class A enzymes, KPC enzymes, class B metallo-β-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.

Within health science programs there has been a call for more faculty development, particularly for teaching and learning. The primary objectives of this review were to describe the current landscape for faculty development programs for teaching and learning and make recommendations for the implementation of new faculty development programs. A thorough search of the pertinent health science databases was conducted, including the Education Resource Information Center (ERIC), MEDLINE, and EMBASE, and faculty development books and relevant information found were reviewed in order to provide recommendations for best practices. Faculty development for teaching and learning comes in a variety of forms, from individuals charged to initiate activities to committees and centers. Faculty development has been effective in improving faculty perceptions on the value of teaching, increasing motivation and enthusiasm for teaching, increasing knowledge and behaviors, and disseminating skills. Several models exist that can be implemented to support faculty teaching development. Institutions need to make informed decisions about which plan could be most successfully implemented in their college or school.

The harlequin bug, Murgantia histrionica (Hahn), is an agricultural pest in the continental United States, particularly in southern states. Reliable gene sequence data are especially useful to the development of species-specific, environmentally friendly molecular biopesticides and effective biolures for this insect. Here, mRNAs were sampled from whole insects at the 2nd and 4th nymphal instars, as well as sexed adults, and sequenced using Illumina RNA-Seq technology. A global assembly of these data identified 72,540 putative unique transcripts bearing high levels of similarity to transcripts identified in other taxa, with over 99% of conserved single-copy orthologs among insects being detected. Gene ontology and protein family analyses were conducted to explore the functional potential of the harlequin bug’s gene repertoire, and phylogenetic analyses were conducted on gene families germane to xenobiotic detoxification, including glutathione S-transferases, carboxylesterases and cytochrome P450s. Genic content in harlequin bug was compared with that of the closely related invasive pest, the brown marmorated stink bug, Halyomorpha halys (Stål). Quantitative analyses of harlequin bug gene expression levels, experimentally validated using quantitative real-time PCR, identified genes differentially expressed between life stages and/or sexes.

To assess health care providers' perceptions of student pharmacists involved as members of a general medicine team. A brief, anonymous, online survey instrument was distributed to 134 health care providers at 4 major medical centers in Massachusetts who interacted with Northeastern University student pharmacists during inpatient general medicine advanced pharmacy practice experiences beginning in March 2011. The survey instrument assessed health care provider perception of student pharmacists' involvement, preparedness, clinical skills, and therapeutic recommendations. Of the 79 providers who responded, 96.2% reported that student pharmacists were prepared for medical rounds and 87.3% reported that student pharmacists were active participants in patient care. Also, 94.9% and 98.7% of providers indicated that student pharmacist recommendations were appropriate and accurate, respectively. The majority (61.8%) of providers believed that student pharmacist involvement on internal medicine teams was beneficial. Provider perceptions regarding student pharmacist participation on general medicine practice experiences were mostly positive.

Objective. To implement and assess the curricular integration of the Pharmacists’ Patient Care Process (PPCP) in a course series for second- and third-year pharmacy students. Methods. The five-step PPCP was integrated within a four-semester pharmacotherapy course starting with the introductory course lectures. Beginning in the spring of 2015, the five steps of the PPCP were delivered to 129 P2 students, along with rollout of curricular integration within corresponding classroom and seminar activities and assessments. Integration focused on the development of course-specific lecture and seminar materials, a faculty guidance strategy and templates, and evaluation approaches for course assessments. Student comprehension and utilization of the PPCP were assessed via 61 unique assessments (12 examinations and 49 quizzes). Faculty incorporation and perception of the PPCP were evaluated via survey. Results. Overall, students demonstrated the most understanding on the lowest levels of the PPCP: 83.6% and 82.2% for the Collect and Implement components, respectively, compared to the higher-level components of Planning (78.0%) and Follow-up (76.0%). Faculty understanding, integration, and utilization of the PPCP in course materials were assessed approximately 6 months after implementation. Twenty-two faculty (96% of course instructors) participated in the survey. Eighteen (82%) have modified instructional materials to incorporate PPCP and among these, 89% agreed/strongly agreed that they possessed a clear understanding of the PPCP. Conclusion. Implementing a successful curricular change such as the integration of the PPCP across multiple courses requires a multi-faceted approach. The development of faculty templates and provision of support through various methods are necessary to ensure consistent and comprehensive integration across the curriculum. Additionally, evaluation of student performance and achievement of intended outcomes should be used to guide curricular assessments and continuous quality improvements throughout the process.