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.

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.

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.

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.

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.

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.

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.

Teplizumab for treatment of type 1 diabetes mellitus.

OBJECTIVE: To review the pharmacology, pharmacokinetics, safety, and efficacy of teplizumab and evaluate relevant clinical trial data. DATA SOURCES: Searches of MEDLINE, International Pharmaceutical Abstracts, ClinicalTrials.gov, American Diabetes Association scientific posters, and Google Scholar (1966-May 2012) were conducted using the key words teplizumab, anti-CD3 monoclonal antibody, MGA031, and hOKT3γ1 (Ala-Ala). Searches were limited to articles published in English. STUDY SELECTION AND DATA EXTRACTION: Clinical trials evaluating teplizumab for type 1 diabetes mellitus (T1DM) published in English were selected from the data sources. All published relevant abstracts were included. References cited in identified articles were used for additional citations. DATA SYNTHESIS: T1DM accounts for up to 10% of all cases of diabetes mellitus. T1DM is characterized as a chronic and progressive autoimmune disease leading to the destruction of insulin-producing ß-cells of the pancreas. Teplizumab is a humanized Fc-mutated anti-CD3 monoclonal antibody that alters the function of the T-lymphocytes that mediate the destruction of the insulin-producing ß-cells. While clinical data are limited, both Phase 2 and Phase 3 studies have demonstrated preserved C-peptide response as a measure of insulin production, decreased exogenous insulin use, and improved glycemic control following a 12- to 14-day teplizumab infusion in patients diagnosed with T1DM within the previous 6 weeks. However, 1 Phase 3 trial failed to find the same benefits in those diagnosed with T1DM within the previous 12 weeks when a lower cumulative teplizumab dose was used. Initial studies indicated that teplizumab is well tolerated, with a self-limiting rash as the most commonly reported adverse effect. CONCLUSIONS: Teplizumab is an anti-CD3 human monoclonal antibody with promising activity in treatment of patients with T1DM. Results from Phase 3 trials are needed to further determine safety, efficacy, and dosing frequency.

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.

Milnacipran for treatment of fibromyalgia.

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of milnacipran and evaluate relevant clinical trial data. DATA SOURCES: MEDLINE, International Pharmaceutical Abstracts, and Google Scholar searches (1966-June 2010) were conducted using the key words fibromyalgia, milnacipran, and serotonin-norepinephrine reuptake inhibitor. Searches were limited to articles published in English. STUDY SELECTION AND DATA EXTRACTION: All available English-language articles of human studies were evaluated. One pharmacokinetic study reviewed included animal data. References cited in identified articles were used for additional evaluation. DATA SYNTHESIS: Milnacipran is a serotonin-norepinephrine reuptake inhibitor with a 3-fold increased selectivity for norepinephrine compared to serotonin. It is well absorbed with 85-90% bioavailability. Maximum concentrations are achieved 2-4 hours after administration. Milnacipran does not undergo cytochrome P450 metabolism and has a half-life of 6-8 hours. Fifty-five percent of each dose is excreted unchanged in the urine. Dose adjustment is needed in patients with an estimated creatinine clearance of <30 mL/min. Clinical trials indicated that twice-daily dosing at 100 mg/day or 200 mg/day was superior to single-daily dosing. Studies further established the effectiveness of both doses in the treatment of fibromyalgia pain utilizing patient self-reported pain scores, as well as on a visual analog scale, Patient Global Impression of Change scale, and the Short-Form 36 Physical Component Summary. A 6-month extension trial, which evaluated patients continued on milnacipran for up to 1 year, demonstrated continued pain relief. The most common adverse drug reaction associated with milnacipran was nausea, which was reduced with slow-dose titration and administration with food. CONCLUSIONS: Milnacipran is an effective treatment option for patients with fibromyalgia. More head-to-head clinical trials are necessary to assess its ultimate place in therapy.

Assessing the clinical efficacy of sildenafil for the treatment of female sexual dysfunction.

OBJECTIVE: To review the clinical data regarding the efficacy and safety of sildenafil for the treatment of female sexual dysfunction (FSD). DATA SOURCES: A MEDLINE search from 1950 to February 2009 was conducted using the key words sildenafil and female sexual dysfunction. Human studies and publication in English were used as primary limits. A combination of several publication-type limits was used to locate the clinical trials (eg, clinical trial, controlled clinical trial, randomized clinical trial). A bibliographic search was also performed of all located articles. STUDY SELECTION AND DATA EXTRACTION: Clinical trials involving sildenafil treatment of premenopausal and postmenopausal women with FSD and women with FSD due to concomitant medications and/or disease states were reviewed. DATA SYNTHESIS: An increasing number of clinical trials have been published regarding the treatment of FSD with sildenafil. Eight studies demonstrated a possible benefit from treatment for FSD in patients receiving sildenafil, regardless of dose, while 4 trials did not show any significant differences with treatment. It appears that sildenafil might be beneficial for women with FSD caused by diseases such as multiple sclerosis, type 1 diabetes, spinal cord injury, and use of antidepressant medications. CONCLUSIONS: Although data suggest a possible role of sildenafil for the treatment of FSD, the information should be interpreted cautiously, as many of the studies included small sample sizes, used inappropriate statistical tests, and used nonvalidated assessment tools. A better FSD classification system and consistent use of validated assessment tools might help alleviate differences among clinical trials and provide a more cohesive foundation for assessing the safety and efficacy of sildenafil for the treatment of FSD.

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.

Oral varenicline for smoking cessation.

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of varenicline and provide a review of relevant clinical data. DATA SOURCES: A MEDLINE search (2001-December 2006) was conducted using the key words varenicline and nicotine replacement therapy for clinical trials limited to human subjects and published in English. STUDY SELECTION AND DATA EXTRACTION: All available human trials of varenicline were selected for review. References cited in identified articles were used for additional citations. DATA SYNTHESIS: Varenicline selectively targets the alpha4beta2 nicotine receptors in the brain that are responsible for cravings and withdrawal associated with nicotine use and dependence. Maximal plasma concentration occurs within 3-4 hours after administration and, after multiple doses, a steady-state concentration is reached within 4 days. Varenicline has a half-life of 24 hours. Oral bioavailability is not affected by food or time of administration. It exhibits linear pharmacokinetics and low plasma protein binding (< or =20%) regardless of a patient's age and renal status. It can be administered once daily. Dosage adjustments are not required in patients with hepatic insufficiency, but adjustments may be necessary in patients with severe renal insufficiency. Clinically significant drug-drug interactions have not been observed with varenicline or co-inhibitors of the human organic cation transporter, which mediates renal secretion of varenicline. Substrates such as warfarin, digoxin, cimetidine, metformin, bupropion, and transdermal nicotine do not alter pharmacokinetic parameters when coadministered with varenicline. In vitro studies have not demonstrated alterations in cytochrome P450 enzyme parameters. Varenicline's safety with coadministration of nicotine replacement products has not been well established. CONCLUSIONS: Varenicline is an effective oral agent for smoking cessation.

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.

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.

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.

Clinical versus statistical significance: interpreting P values and confidence intervals related to measures of association to guide decision making.

Pharmacists need to apply outcomes from studies to reduce risk and improve patient care. Interpretation of outcomes is based on a variety of assessment tools, such as P values and confidence intervals (CIs). P values determine statistical significance of data, while CIs suggest the degree of clinical application. Many health care providers might not have the skill set required to carefully examine and interpret statistical results and then are required to assume that the researchers of the study correctly interpreted and presented the statistical results. The reluctance to examine statistical data often reflects a misconception that concepts such as P values and CIs are difficult to understand, while in reality, both can be interpreted once basic definitions and applications are understood. Measures of association such as number needed to treat can serve as effective tools for quantifying important parameters that ultimately affect patient care. A basic understanding of how to interpret and apply P values and CIs enhances one's ability to effectively assess the validity of results from the literature. An informed reader, armed with tools for critical analysis, is in the best position to evaluate studies and thereby discern which information is applicable to a specific patient care decision.