Public health impact of 2-, 4-, and 9-valent HPV vaccination in females on cervical and noncervical diseases in men and women under different coverage scenarios in China: A simulation study.

The high prevalence of human papillomavirus (HPV) infection in China suggests there would be a substantial positive health impact of widespread vaccination against HPV. We adapted a previously described dynamic transmission model of the natural history of HPV infection and related diseases to the Chinese setting to estimate the public health impact in China of 2-valent (with and without cross-protection), 4-valent, and 9-valent HPV vaccination strategies. The model predicted the incidence and mortality associated with HPV-related diseases, including cervical and noncervical cancers, genital warts, and recurrent respiratory papillomatosis (RRP), based on the various vaccination coverage rate (VCR) scenarios, over a 100-year time horizon. The public health impact of the 4 vaccination strategies was estimated in terms of cases and deaths averted compared to a scenario with no vaccination. Under the assumption of various primary and catch-up VCR scenarios, all 4 vaccination strategies reduced the incidence of cervical cancer in females and noncervical cancers in both sexes, and the 4-valent and 9-valent vaccines reduced the incidence of genital warts and RRP in both sexes. The 9-valent vaccination strategy was superior on all outcomes. The number of cervical cancer cases averted over 100 years ranged from ~ 1 million to ~ 5 million while the number of cervical cancer deaths averted was ~ 345,000 to ~ 1.9 million cases, depending on the VCR scenario. The VCR for primary vaccination was the major driver of cases averted.

Managing the Drug-Drug Interaction With Apixaban and Primidone: A Case Report.

The management of the drug-drug interaction (DDI) between primidone, a moderate to strong cytochrome P-450 (CYP) 3A4 inducer, and apixaban, a direct oral anticoagulant (DOAC) and CYP3A4 substrate is complex and limited evidence exists to guide management. This case report describes a 65-year-old male, receiving primidone for essential tremor who developed an acute venous thromboembolism (VTE) requiring oral anticoagulation. DOACs are preferred over vitamin K antagonists for acute VTE treatment. Based on patient-specific variables, provider preference, and the avoidance of other DDIs, apixaban was selected. Apixaban's package insert recommends avoiding use with concomitant strong P-gp and CYP3A4 inducers due to the decreased exposure to apixaban; however, no recommendations are available for drugs that are moderate to strong CYP3A4 inducers and lack P-gp effects. Given that phenobarbital is an active metabolite of primidone, extrapolation of evidence from such literature is theoretical but provides insight into the management of this multi-faceted DDI. In the absence of the ability to monitor plasma apixaban levels, a management strategy of avoidance with a washout period of primidone based on pharmacokinetic parameters was used in this case. Additional evidence is needed to clearly understand the degree of impact and clinical significance of the DDI between apixaban and primidone.

Evaluating the Impact of a Pharmacist-Led Antimicrobial Stewardship Intervention at Discharge in a Community, Nonteaching Hospital.

INTRODUCTION: Approximately 30% to 50% of hospital discharge antimicrobials are inappropriate. Limited data exist on approaches to improve antimicrobial prescribing practices at the time of discharge from a community hospital. Objective: To assess the impact of a comprehensive pharmacist-led antimicrobial stewardship intervention at discharge. METHODS: We conducted a quasi-experimental, pre-post study. A biphasic intervention took place on 2 medicine units from November 2019 to May 2020 at a community hospital. Baseline data were collected, followed by prescriber education on antimicrobial stewardship to both units (education phase). Next, a pharmacist-led intervention took place on one unit (intervention phase). The primary outcome was composite appropriateness of an oral antimicrobial prescribed to an adult at the time of discharge, defined by narrow spectrum of activity, dosing, and duration of therapy. The primary outcome was assessed using Fisher exact test. RESULTS: Baseline composite appropriateness was 30% (n = 12) on the control unit and 30.8% (n = 20) on the intervention unit. From baseline to posteducation, no significant change in composite appropriateness was found on the control (30% to 26.7%, P = 0.256) or intervention (30.8% to 19.4%, P = 0.09) unit. There was no significant difference between the education to intervention phase (26.7% vs 35%, P = 0.254) on the control unit. On the intervention unit, a significant difference in composite appropriateness was found from the education to intervention phase (19.4% vs 47.8%, P = 0.017). CONCLUSION AND RELEVANCE: A pharmacist-led intervention improved appropriateness of oral antimicrobials prescribed at discharge. One-time education was insufficient for improving antimicrobial stewardship.

Evaluating the Use of Digital Biomarkers to Test Treatment Effects on Cognition and Movement in Patients with Lewy Body Dementia.

BACKGROUND: PRESENCE was a Phase 2 trial assessing mevidalen for symptomatic treatment of Lewy body dementia (LBD). Participants received daily doses (10, 30, or 75 mg) of mevidalen (LY3154207) or placebo for 12 weeks. OBJECTIVE: To evaluate if frequent cognitive and motor tests using an iPad app and wrist-worn actigraphy to track activity and sleep could detect mevidalen treatment effects in LBD. METHODS: Of 340 participants enrolled in PRESENCE, 238 wore actigraphy for three 2-week periods: pre-, during, and post-intervention. A subset of participants (n = 160) enrolled in a sub-study using an iPad trial app with 3 tests: digital symbol substitution (DSST), spatial working memory (SWM), and finger-tapping. Compliance was defined as daily test completion or watch-wearing ≥23 h/day. Change from baseline to week 12 (app) or week 8 (actigraphy) was used to assess treatment effects using Mixed Model Repeated Measures analysis. Pearson correlations between sensor-derived features and clinical endpoints were assessed. RESULTS: Actigraphy and trial app compliance was > 90% and > 60%, respectively. At baseline, daytime sleep positively correlated with Epworth Sleepiness Scale score (p < 0.01). Physical activity correlated with improvement on Movement Disorder Society -Unified Parkinson Disease Rating Scale (MDS-UPDRS) part II (p < 0.001). Better scores of DSST and SWM correlated with lower Alzheimer Disease Assessment Scale -Cognitive 13-Item Scale (ADAS-Cog13) (p < 0.001). Mevidalen treatment (30 mg) improved SWM (p < 0.01), while dose-dependent decreases in daytime sleep (10 mg: p < 0.01, 30 mg: p < 0.05, 75 mg: p < 0.001), and an increase in walking minutes (75 mg dose: p < 0.001) were observed, returning to baseline post-intervention. CONCLUSION: Devices used in the LBD population achieved adequate compliance and digital metrics detected statistically significant treatment effects.

A Continuing Education Activity Durably Addressed Knowledge Gaps Related to Penicillin Allergies Among Pharmacists and Pharmacy Technicians.

Background: Penicillin allergy is one of the most frequent self-reported allergies; however, only about 10% of reported allergies are accurate. Objectives: Through the creation of a continuing pharmacy education (CPE) activity, we sought to assess knowledge gaps and comfort levels in the management of penicillin allergies. Methods: A 1-hour enduring-content CPE activity was offered as an interactive course from September 20, 2019, to September 20, 2020. Participants completed 3 surveys (pre-survey, post-survey, and follow-up survey). Participants were pharmacists and pharmacy technicians who completed, at a minimum, the activity and both pre- and post-surveys. The primary outcome was the percentage of participants scoring >80% on knowledge-based questions on the post-survey compared with the pre-survey. Secondary outcomes included pre-post comparisons on knowledge-based questions, participants' self-report of an allergy, and comfort levels dispensing cephalosporins in a patient with a self-reported penicillin allergy. Results: A total of 389 participants completed the CPE activity, with 176 included for analysis. Significantly more participants scored >80% on knowledge-based questions on the post-survey compared with the pre-survey (71.6% vs 22.7%, P < .001). There was no significant difference between the percentage of participants scoring >80% on the post-survey and the follow-up survey (71.6% vs 65%, P = .119). The majority of participants (74%) felt comfortable dispensing a cephalosporin in a patient with a penicillin allergy on the pre-survey, with similar percentages on the post- and follow-up surveys (77% and 90%, respectively). Conclusion: A targeted continuing education program improved overall knowledge, which was sustained for up to 2 months.

Successful Use of Apixaban for Paget-Schroetter Syndrome in a Pediatric Patient.

Paget-Schroetter syndrome (PSS) is a rare syndrome that typically develops in young, healthy males subjected to repetitive overhead motions resulting in compression and thrombosis of the subclavian vein. This "effort thrombosis" typically occurs acutely in patients with specific anatomic variations within the thoracic outlet and is treated by a combination of surgical and pharmacologic interventions. There is a paucity of literature regarding this syndrome, particularly surrounding pharmacotherapy, and in the treatment of pediatric patients. This case report documents the pharmacologic treatment of a 17-year-old, male, baseball player with confirmed PSS. Apixaban was selected as the anticoagulant therapy of choice following the determination of its safety and anticipated efficacy for this pediatric patient. Upon admission, anticoagulation was initiated with intravenous heparin and transitioned to warfarin for 1 dose. On day 2, the patient was discharged with apixaban 10 mg twice daily for 7 days, followed by 5 mg twice daily. One week later, he underwent catheter-directed thrombectomy, followed by thoracic outlet decompression with resection of the first rib. Apixaban therapy was continued for 10 weeks after the procedure to diminish the risk of any further thrombotic events. This pediatric patient with PSS was successfully treated with apixaban in conjunction with surgical management. Treatment with apixaban resulted in continued resolution of thrombus after follow-up, with no complications reported thereafter. Further research is needed to definitively determine the safety and efficacy of apixaban for the use of pediatric anticoagulation, particularly in upper extremity deep vein thrombosis.

Impact of a novel preceptor collaborative advanced pharmacy practice experience curriculum on student-perceived ability and confidence.

BACKGROUND AND PURPOSE: A novel teaching collaborative for acute care medicine advanced pharmacy practice experiences (APPEs) was formed by five faculty preceptors. The primary goal of the collaborative model was to ensure that acute care medicine APPEs provided students with opportunities to achieve Accreditation Council of Pharmacy Education Standards 2016, including strengthening students' ability to be practice- and team-ready. EDUCATIONAL ACTIVITY AND SETTING: The collaborative model included group discussions, video modules, patient cases, journal scans, and case presentations among student pharmacists completing an adult or pediatric acute care APPE. Anonymous, voluntary pre-/post-surveys were completed by a cohort of students who participated in the collaborative model from May 2018 to April 2019. Survey questions assessed student-perceived ability/confidence related to interprofessional (IP) relationships and decision-making skills for adult and pediatric patients, as well as value of activities. FINDINGS: From the cohort of 67 students, 54 pre-survey and 45 post-survey responses were obtained. Post-rotation, students showed an increase in confidence to practice pharmacy on an IP team (39% vs. 100%, P < .001). Significant increases were also found for therapeutic decision-making regarding antibiotics, anticoagulants, and pharmacokinetics for adult and pediatric patients. Among students completing the post-survey, video modules were the most valued component of the model. SUMMARY: A collaborative APPE model resulted in consistent increases in student-perceived ability and confidence related to care of adult and pediatric patients. This APPE model could be adapted within different care settings and pharmacy curricula.

Budget impact analysis of multiple varicella vaccination strategies: a Mexico perspective.

A number of live-attenuated varicella vaccines are produced globally that provide protection against the varicella zoster virus. In Mexico, varicella vaccination is not included in the national immunization program and is recommended for use only in high-risk subgroups. We developed a budget impact model to estimate the impact of universal childhood immunization against varicella on the national payer system in Mexico. A scenario of no varicella vaccination was compared to scenarios with vaccination with a single dose at 13 months of age, in alignment with the existing program of immunization with the measles-mumps-rubella vaccine. Nine different vaccination scenarios were envisioned, differing by vaccine type and by coverage. Varicella cases and treatment costs of each scenario were computed in a dynamic transmission model of varicella epidemiology, calibrated to the population of Mexico. Unit costs were based on Mexico sources or were from the literature. The results indicated that each of the three vaccine types increased vaccine acquisition and administration expenditures but produced overall cost savings in each of the first 10 years of the program, due to fewer cases and reduced varicella treatment costs. A highly effective vaccine at 95% coverage produced the greatest cost savings.

Noncarbapenems for the Treatment of Urinary Tract Infections Caused by Extended-Spectrum ß-Lactamase-Producing Bacteria.

OBJECTIVES: Urinary tract infections (UTIs) caused by extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae are resistant to many conventional therapies, including third-generation cephalosporins. Carbapenems are considered first-line agents for ESBL infections, but their use is associated with increased multidrug resistance and should be reserved when absolutely necessary. Because of the increased rates of UTIs caused by ESBL-producing organisms and incidence of carbapenem resistance, safe and effective alternatives to carbapenems are needed. This study was conducted to evaluate the outcomes associated with the treatment of ESBL UTIs with noncarbapenem antibiotics. METHODS: A retrospective cohort study of adults with ESBL UTIs was conducted at a community hospital. Patients were categorized as those receiving definitive carbapenem therapy and those receiving definitive noncarbapenem therapy. Calculated measurements included infection-related mortality, length of hospital stay, and duration of definitive antibiotic therapy. Microbiological failure was assessed as a secondary outcome. Data on the safety of antibiotic therapy were not collected. P < 0.05 was considered significant. RESULTS: Fifty patients met inclusion criteria for the study, divided evenly between the two cohorts. No statistical differences were observed for length of hospital stay (P = 0.601), duration of therapy (P = 0.398), or rate of microbiological failure between the groups (P = 0.115). CONCLUSIONS: Noncarbapenems did not demonstrate significant differences compared with carbapenems in the treatment of adults with ESBL UTIs. In certain patient populations, noncarbapenems that demonstrate in vitro activity may be appropriate for UTIs caused by ESBL-producing organisms.

Cost-effectiveness analysis of universal varicella vaccination in Turkey using a dynamic transmission model.

BACKGROUND: In 2013, Turkey introduced one-dose universal varicella vaccination (UVV) at 12 months of age. Inclusion of a second dose is being considered. METHODS: We developed a dynamic transmission model to evaluate three vaccination strategies: single dose at 12 months (1D) or second dose at either 18 months (2D-short) or 6 years of age (2D-long). Costs and utilization were age-stratified and separated into inpatient and outpatient costs for varicella and herpes zoster (HZ). We ran the model including and excluding HZ-related costs and impact of exogenous boosting. RESULTS: Five years post-introduction of UVV (1D), the projected varicella incidence rate decreases from 1,674 cases pre-vaccine to 80 cases/100,000 person-years. By 25 years, varicella incidence equilibrates at 39, 12, and 16 cases/100,000 person-years for 1D, 2D-short, and 2D-long strategies, respectively, using a highly effective vaccine. With or without including exogenous boosting impact and/or HZ-related costs and health benefits, the 1D strategy is least costly, but 2-dose strategies are cost-effective considering a willingness-to-pay threshold equivalent to the gross domestic product. The model predicted a modest increase in HZ burden during the first 20-30 years, after which time HZ incidence equilibrates at a lower rate than pre-vaccine. CONCLUSIONS: Our findings support adding a second varicella vaccine dose in Turkey, as doing so is highly cost-effective across a wide range of assumptions regarding the burden associated with varicella and HZ disease.

The Importance of Authentic Leadership to all Generations Represented within Academic Pharmacy.

Academic pharmacy spans several generations including traditionalists, baby boomers, Generation X, and Generation Y, commonly referred to as millennials. It has been suggested that leadership styles must change to accommodate these generational differences in academic pharmacy, yet there are no data of which we are aware, that support this assertion. We contend that leadership styles are derived from one's authentic self and are based on core beliefs and values; therefore, leadership styles must not change to accommodate a specific generation or other subset of academic pharmacy. Instead, effective leaders must change tactics (ie, methods or processes) to reach and influence a specific cohort. This article develops and supports the argument that leadership styles should not change to accommodate generational differences in academic pharmacy.

The role of adenotonsillectomy in the treatment of primary nocturnal enuresis in children: A systematic review.

INTRODUCTION: Primary nocturnal enuresis (PNE) is a challenging condition for physicians, patients and families. Although the etiology remains unclear, sleep-disordered breathing (SDB) and sleep apnea have been suggested to play an important role. Recent research has suggested a potential therapeutic benefit of adenotonsillectomy (T&A) and surgical management of upper airway obstruction in the treatment of PNE. OBJECTIVE: The aim was to conduct a systematic review of relevant literature to determine the effectiveness of T&A in treating children aged 2-19 years with PNE. STUDY DESIGN: This was a systematic review using a comprehensive electronic search strategy that included PubMed, Embase, CINAHL, Cochrane Library, conference proceedings, and the gray literature up to July 2015. We included all studies of children aged 2-19 years with PNE and SDB who underwent T&A. The primary outcome was resolution of PNE following surgery. Observational studies and randomized trials were reviewed. Risk of bias assessment and meta-analyses of included studies were performed. RESULTS: We screened 3254 citations; following title and abstract screening, 42 studies were selected for full-text screening by two independent reviewers. We included 18 studies (890 patients) in our final analysis. All studies were observational and only one included a control group. Meta-analysis of proportions of all (18) studies revealed a pooled complete resolution rate of 51% (43-60%), with significant heterogeneity among studies (I2 = 82.2%). Partial resolution was seen in 20% (14-27%), with similar heterogeneity to the complete resolution group. Sensitivity analysis including only studies with a low risk of bias and with patients ≥5 years (n = 244 patients) yielded a complete resolution rate of 43% (36-49%) with minimal heterogeneity (I2 = 0%; figure). CONCLUSION: In our systematic review, T&A resulted in improvement of nocturnal enuresis in more than 60% of patients, with complete resolution rates in excess of 50%. Findings were persistent on meta-analysis focused only on studies including older patients (≥5 years) and those with short follow-up after surgery (≤3 months), which imply a higher cure rate than would be expected based on natural history alone. The limitations of this review include the lack of controlled trials, the overall quality of the evidence reviewed and the heterogeneity between included studies. The role for systematic investigation and treatment of sleep disorders in patients with PNE should be scrutinized further, since a near 50% complete resolution rate for PNE may be expected with T&A in some settings.

Novel oral anticoagulants for heparin-induced thrombocytopenia.

To review the use of the novel oral anticoagulant (NOAC) agents for the treatment of heparin-induced thrombocytopenia (HIT) from relevant clinical trial data. A MEDLINE, International Pharmaceutical Abstracts, ClinicalTrials.gov, and Google-Scholar searches (1966-March 2016) were conducted using the keywords: thrombocytopenia, NOACs, dabigatran, apixaban, rivaroxaban, edoxaban, Xa inhibitor, direct thrombin inhibitor. Articles evaluating the new oral anticoagulants for thrombocytopenia published in English and using human subjects were selected. Eight clinical trials were identified. References cited in identified articles were used for additional citations. Approximately 12 million hospitalized patients each year are exposed to heparin for thromboprophylaxis. HIT, an immune-mediated, prothrombotic adverse reaction is a potential complication of heparin therapy. As a result, heparin products must be immediately withdrawn and replaced by alternative anticoagulants to compensate for the thrombotic risk associated with HIT. Limitations exist with the only currently FDA approved heparin alternative, argatroban. NOACs have been considered as potential alternatives to traditional agents based on their pharmacologic activity. Case reports have indicated positive results in patients, with clinical outcomes and tolerability supporting the use of the NOACs as alternative agents in the treatment of HIT. Positive results have been reported for the use of NOACs in the treatment of HIT. Further robust studies are needed for definitive decision making by clinicians.

Time to Guideline-Based Empiric Antibiotic Therapy in the Treatment of Pneumonia in a Community Hospital: A Retrospective Review.

PURPOSE: The 2005 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines for hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and health care-associated pneumonia (HCAP) stress the importance of initiating prompt appropriate empiric antibiotic therapy. This study's purpose was to determine the percentage of patients with HAP, VAP, and HCAP who received guideline-based empiric antibiotic therapy and to determine the average time to receipt of an appropriate empiric regimen. METHODS: A retrospective chart review of adults with HAP, VAP, or HCAP was conducted at a community hospital in suburban Birmingham, Alabama. The hospital's electronic medical record system utilized International Classification of Diseases, Ninth Revision (ICD-9) codes to identify patients diagnosed with pneumonia. The percentage of patients who received guideline-based empiric antibiotic therapy was calculated. The mean time from suspected diagnosis of pneumonia to initial administration of the final antibiotic within the empiric regimen was calculated for patients who received guideline-based therapy. RESULTS: Ninety-three patients met the inclusion criteria. The overall guideline adherence rate for empiric antibiotic therapy was 31.2%. The mean time to guideline-based therapy in hours:minutes was 7:47 for HAP and 28:16 for HCAP. For HAP and HCAP combined, the mean time to appropriate therapy was 21:55. CONCLUSION: Guideline adherence rates were lower and time to appropriate empiric therapy was greater for patients with HCAP compared to patients with HAP.

Enzymatic Stability of Alteplase Solution for Injection: Effect of Various Methods of Thawing Frozen Solutions.

Objective: To modify and evaluate an established chromogenic assay protocol for measuring plasminogen activator inhibitor type-1 (PAI-1) activity to measure tissue plasminogen activator (tPA) activity and compare the enzymatic activity of alteplase as a function of the conditions under which it is thawed. Methods: A 50 mg vial of alteplase was reconstituted with sterile water to make a 1 mg/mL stock solution (nominal concentration). Plastic syringes were loaded with 0.5 mL of alteplase stock solution and stored at -20°C. After 8 days, samples were thawed by 3 methods - via body temperature (37°C), room temperature (20°C), or in a refrigerator (2°C). Thaw times were recorded. The thawed solutions, along with a freshly prepared alteplase solution, were assayed using the modified protocol of the Spectrolyse PAI-1 kit to determine residual tPA enzyme activity. Results: Validation of the modified protocol for the Spectrolyse PAI-1 kit used to measure tPA activity produced a linear response with coefficients of determination (R2) of greater than 0.9977 when assayed on 2 separate days, which corresponded to an enzymatic activity accuracy between 98.3% and 108.3%. The average percent residual tPA enzyme activity of samples from each group compared to the freshly prepared solution was 106%, 98.7%, and 91.5% for samples thawed at body temperature, room temperature, and refrigerated, respectively. Conclusion: Modifications to the standard procedure for the Spectrolyse PAI-1 kit allows for accurate determination of tPA activity in aqueous based reconstituted solutions of alteplase. Under thawed conditions, alteplase retained greater than 91% enzyme activity as compared to a freshly prepared control.

A review of the efficacy and safety of canagliflozin in elderly patients with type 2 diabetes.

OBJECTIVE: To review the efficacy and safety of canagliflozin (CAN) in elderly patients with type 2 diabetes mellitus (T2DM). DATA SOURCES: Studies were identified using PubMed, International Pharmaceutical Abstracts, MEDLINE, Academic Search Premier, SCOPUS, and Google Scholar from 2011 to August 2013. The following key words were reviewed: canagliflozin, canagliflozin elderly, canagliflozin geriatrics, dapagliflozin, sodium glucose cotransporter 2 (SGLT2) inhibitors, and SGLT2 receptor inhibitors. DATA EXTRACTION: Articles evaluating CAN for diabetes that were published in English and used human subjects were selected. Fifteen clinical trials were identified and evaluated. STUDY SELECTION: Of 15 identified articles, 2 articles, 2 published posters, and unpublished information from the manufacturer were chosen based on the mean age of the study subjects. DATA SYNTHESIS: Evidence that elderly patients with T2DM have less A1C reduction with CAN is presented; the benefit on A1C is significant. Systolic blood pressure (SBP) and body weight reduction in the elderly were consistent with younger patients. Adverse effects such as increased urinary frequency, genital mycotic infections, and urinary tract infections may discourage the use of CAN in the elderly patient. CONCLUSION: Treatment with CAN improves A1C levels, reduces SBP and body weight, and is overall well tolerated in older subjects with T2DM. Risks and benefits of treatment with CAN should be assessed in geriatric patients on a case-by-case basis. Safety in elderly patients was consistent with that of other phase 3 trials in the general population. Additional longterm cardiovascular studies are needed.

Aclidinium bromide for the treatment of chronic obstructive pulmonary disease.

PURPOSE: The safety and efficacy of the second U.S.-approved long-acting inhaled anticholinergic for controlling bronchospasm in patients with chronic obstructive pulmonary disease (COPD) are reviewed. SUMMARY: Aclidinium bromide (Tudorza, Forest Pharmaceuticals) is indicated for long-term maintenance therapy for COPD-associated bronchospasm. It is marketed as a 60-dose metered-dose inhaler to be used twice daily. In Phase II and III clinical trials involving a total of more than 3000 patients, daily use of aclidinium bromide was found to significantly improve selected key indicators of lung function (trough values for forced expiratory volume at one second [FEV1] and other FEV1 outcome measures) compared with placebo use. Other benefits of aclidinium bromide therapy, including a significant reduction in nighttime COPD symptoms, were demonstrated for up to one year. However, aclidinium bromide has not been consistently demonstrated to be more effective than the other currently available long-acting inhaled anticholinergic, tiotropium bromide. Furthermore, the clinical trials indicated no significant difference between aclidinium bromide and tiotropium bromide with regard to rates of systemic adverse effects. For some patients, aclidinium bromide may offer advantages over tiotropium bromide (e.g., a faster time to peak FEV1, lower cost of therapy). CONCLUSION: Aclidinium bromide is an inhaled anticholinergic that improves lung function measures in patients with COPD. The most common adverse effects during clinical trials of the drug were headache, nasopharyngitis, and cough, none of which occurred at significantly higher rates than were seen with placebo use.

Dolutegravir: An Integrase Strand Transfer Inhibitor for the Treatment of Human Immunodeficiency Virus 1 in Adults.

Objective: To review the efficacy, safety, pharmacokinetics, pharmacodynamics, administration, drug interactions, and cost of dolutegravir (Tivicay), a third in class integrase strand transfer inhibitor (INSTI), for the treatment of human immunodeficiency virus (HIV-1) in adults. Data Sources: MEDLINE, International Pharmaceutical Abstracts, ClinicalTrials.gov, and Google Scholar searches (January 2000 to May 2014) were conducted for articles published in English and limited to human subjects, using the key words antiretroviral drugs, HIV integrase strand transfer inhibitors, dolutegravir, DTG, and S/GSK1349572. Study Selection and Data Extraction: Following MEDLINE, International Pharmaceutical Abstracts, ClinicalTrials.gov, and Google Scholar searches, 6 clinical trials were identified and included in this review. Phase III/IV studies evaluating the safety and efficacy of dolutegravir in humans were selected and evaluated. Data Synthesis: In treatment naïve and experienced patients dolutegravir was noninferior to raltegravir at suppressing viral load when added to background therapy. Abacavir/lamivudine/dolutegravir was noninferior to efavirenz/emtricitabine/tenofovir disoproxil fumarate and darunavir/ritonavir plus background therapy at suppressing viral load. In patients with multiple-class antiretroviral resistance at baseline, dolutegravir decreased HIV RNA by 1.4 log10 copies/mL at day 8, 63% of patients had achieved virologic suppression at week 8, and retained potency in treatment-experienced INSTI-resistant patients up to week 48 or 96 of follow-up. Conclusion: Dolutegravir is a safe, effective, and well-tolerated treatment option for adults with HIV-1, even in the setting of resistance to other antiretrovirals.

Avanafil for erectile dysfunction.

OBJECTIVE: To review the pharmacology, pharmacokinetics, safety, and efficacy of avanafil and evaluate relevant clinical trial data. DATA SOURCES: A MEDLINE, International Pharmaceutical Abstracts, ClinicalTrials.gov, and Google Scholar searches (1966 to July 2013) were conducted using the key words: avanafil, erectile dysfunction, and phosphodiesterase type 5 (PDE5) inhibitor. STUDY SELECTION AND DATA EXTRACTION: Articles evaluating avanafil for erectile dysfunction (ED) published in English and using human subjects were selected. Five clinical trials were identified. References cited in identified articles were used for additional citations. DATA SYNTHESIS: Avanafil is a highly selective PDE5 inhibitor that is a competitive antagonist of cyclic guanosine monophosphate. Specifically, avanafil has a high ratio of inhibiting PDE5 as compared with other PDE subtypes allowing for the drug to be used for ED while minimizing adverse effects. Absorption occurs quickly following oral administration with a median Tmax of 30 to 45 minutes and a terminal elimination half-life of 5 hours. Additionally, it is predominantly metabolized by cytochrome P450 3A4. As such, avanafil should not be co-administered with strong cytochrome P450 3A4 inhibitors. Dosage adjustments are not warranted based on renal function, hepatic function, age or gender. Five clinical trials suggest that avanafil 100 and 200 mg doses are effective in improving the Sexual Encounter Profile and the Erectile Function Domain scores among men as part of the International Index of Erectile Function. A network meta-analysis comparing the PDE5 inhibitors revealed avanafil was less effective on Global Assessment Questionnaire question 1 while safety data indicated no major differences among the different PDE5 inhibitors. The most common adverse effects reported from the clinical trials associated with avanafil were headache, flushing, nasal congestion, nasopharyngitis, sinusitis, and dyspepsia. CONCLUSIONS: Avanafil is a potent PDE5 inhibitor and is an effective treatment option for ED.

A review of warfarin dosing with concurrent acetaminophen therapy.

Warfarin is frequently used for the prevention and treatment of thromboembolism, yet it is associated with numerous drug interactions. Regarding over-the-counter pain medications, the preferred analgesic for those patients who are taking warfarin is acetaminophen. There are, however, reports of elevation in the international normalized ratio (INR) in those patients taking concurrent warfarin and acetaminophen. For those practitioners who manage warfarin therapy, there is little guidance regarding management of the drug-drug interaction between warfarin and acetaminophen. This review seeks to evaluate the drug interaction between warfarin and acetaminophen and provides recommendations for concurrent use of these drugs.