Retrospective, multicenter analysis of the safety and effectiveness of direct oral anticoagulants for the treatment of venous thromboembolism in obesity.

BACKGROUND: Direct 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. METHODS: This 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. RESULTS: There 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). CONCLUSION: There 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.

Impact of antibiotic choice on readmission in adults experiencing an acute COPD exacerbation.

PURPOSE: The impact of antibiotic therapy in managing acute chronic obstructive pulmonary disease (COPD) exacerbations requiring hospitalization remains unclear. We conducted a study to assess the impact of antibiotic therapy on the rate of 30-day readmission after discharge from a hospital stay for an acute COPD exacerbation. Additional study outcomes analyzed included the effects of antibiotic therapy on hospital length of stay, in-hospital mortality, 90-day and 12-month readmission rates, and time to next COPD exacerbation. METHODS: The study was an institutional review board-approved, retrospective, observational review of adult patients at a tertiary academic medical center. The medical records of patients 18 years of age or older who were hospitalized for an acute COPD exacerbation between January 2008 and December 2014 were evaluated. Included patients were stratified by receipt of guideline-appropriate, guideline-inappropriate, or no antibiotic therapy. Nonparametric data were analyzed using the Kruskal-Wallis test (nonparametric) and categorical data via χ 2 test, respectively. RESULTS: Three hundred twenty-five subjects were included; there were no significant differences in baseline characteristics in the 3 study groups. Sixty-eight percent of patients (n = 223) received antibiotics. The percentage of patients readmitted within 30 days did not differ between cohorts: 11.9% (appropriate therapy) vs 13.2% (nonappropriate therapy) vs 12.2% (no antibiotics) (P = 0.95 for all comparisons). Additionally, no detectable differences in 90-day or 12-month readmission rate, length of hospital day, or in-hospital mortality were found. However, a trend toward increased time to next COPD exacerbation was noted in those receiving antibiotics vs no antibiotics (352 days vs 192 days, P = 0.07). CONCLUSION: Treatment of COPD exacerbations with antibiotics did not impact readmission rates, length of hospital stay, in-hospital mortality, or time to next exacerbation. More investigation is warranted to assess the effect of antibiotics on time to next exacerbation, as well as comparative effectiveness between antibiotic classes.

Update on Treatment Options for Gonococcal Infections.

The incidence of Neisseria gonorrhoeae infections in the United States has grown over the past decade. The most recent data provided by the Centers for Disease Control and Prevention (CDC) indicate that reported cases have increased by almost 10% over the last 5 years. In conjunction with this rise, the presence of multidrug-resistant strains of N. gonorrhoeae has also emerged. The 2015 CDC guidelines recommend dual therapy with intramuscular ceftriaxone and oral azithromycin as first-line treatment, although components of this regimen are met with a high level of resistance. Although ceftriaxone resistance has not yet been reported in the United States, it is only a matter of time before such isolates are detected, thus ushering in a new era of difficult-to-manage uncomplicated gonococcal infection. The potential public health crisis and patient-associated sequelae (e.g., pelvic inflammatory disease, epididymitis, and human immunodeficiency virus infection) linked with untreatable gonorrhea are cause for great concern. To try to stem this tide, a number of new agents targeted against N. gonorrhoeae are being investigated in clinical trials. In this article, we review the various agents, both currently available and under clinical investigation, and provide recommendations for the management of gonococcal infections.

Surface microbiology of the iPad tablet computer and the potential to serve as a fomite in both inpatient practice settings as well as outside of the hospital environment.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Faculty development program models to advance teaching and learning within health science programs.

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.

Providers' perceptions of student pharmacists on inpatient general medicine practice experiences.

OBJECTIVE: To assess health care providers' perceptions of student pharmacists involved as members of a general medicine team. METHODS: 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. RESULTS: 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. CONCLUSIONS: Provider perceptions regarding student pharmacist participation on general medicine practice experiences were mostly positive.

Telaprevir: a hepatitis C NS3/4A protease inhibitor.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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%. CONCLUSION: 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.

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.

'Tech' versus 'talk': a comparison study of two different lecture styles within a Master of Science nurse practitioner course.

BACKGROUND: Generation Y students have a strong preference for technology that has caused educators to re-evaluate their instructional techniques. Limited published literature exists evaluating the benefits of electronic lecture delivery to students enrolled within nursing degree programs, with no publications to date comparing traditional to blended learning modalities. OBJECTIVES: To retrospectively compare student outcomes, including overall course grade and individual examination scores, between two cohorts of students utilizing two distinctly different methods of lecture delivery, traditional and blended. METHODS: IRB approval was granted to retrospectively compare student outcomes from fifty-two students enrolled within Northeastern University's Master of Science Nurse Practitioner degree program. A total of 23 students were enrolled in the traditional section taught in 2010 and 29 students were enrolled in the blended section taught in 2011. Student'st-test was used to compare studied outcomes between each section. A p-value of ≤0.05 was considered to be statistically significant. RESULTS: The students enrolled within blended course scored statistically significantly higher than their counterparts within the traditional course for three of the four studied outcomes, including overall course score. CONCLUSIONS: This study demonstrates that nursing students enrolled within a more technologically advanced course may have improved performance over students enrolled in courses with traditional lecture styles given their generational preferences for learning.

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.

Impact of an institution-specific hospital-acquired pneumonia protocol on the appropriateness of antibiotic therapy and patient outcomes.

STUDY OBJECTIVE: To evaluate the impact of a hospital-acquired pneumonia (HAP) protocol on appropriateness of empiric antibiotic therapy, antibiotic deescalation, antibiotic duration, patient mortality, and length of stay. DESIGN: Before- and after-study of protocol implementation. SETTING: A 450-bed, academic medical center. PATIENTS: One hundred consecutive patients with proven or suspected HAP. INTERVENTION: Implementation of an HAP protocol that was based on the 2005 American Thoracic Society-Infectious Diseases Society of America guidelines and included extensive education of clinicians and monitoring by pharmacists. MEASUREMENTS AND MAIN RESULTS: Before protocol implementation, 50 patients with HAP were evaluated against protocol criteria. After protocol implementation, a second cohort of 50 patients with HAP was evaluated. Compared with the preprotocol group, implementation of the protocol led to an increase in both the proportion of patients who received appropriate empiric antibiotic coverage (17 [34%] vs 31 [62%] patients, p=0.005) and appropriate antibiotic deescalation (21 [42%] vs 36 [72%] patients, p=0.002) according to protocol recommendations but did not affect the appropriateness of empiric antibiotic therapy based on final lung culture data (34 [68%] vs 41 [82%] patients, p=0.11). Compared with the preprotocol group, use of the protocol decreased the duration of intravenous antibiotic therapy (median [range] 9 [2-21] vs 7 [1-16] days, p=0.024), was associated with a trend for a shorter duration of stay in the intensive care unit (median [range] 19 [2-57] vs 11 [3-76] days, p=0.065), and did not significantly affect mortality (5 [10%] vs 8 [16%] patients, p=0.37). Pharmacists performed 59 interventions to support the protocol in 29 patients in the postprotocol group, of which 48% were accepted. CONCLUSIONS: Implementation of an HAP protocol improved appropriate empiric antibiotic use and decreased the duration of antibiotic therapy without adversely affecting patient outcomes.