Roflumilast 0.3% Cream: a Phosphodiesterase 4 Inhibitor for the Treatment of Chronic Plaque Psoriasis.

BACKGROUND: Plaque psoriasis is a chronic dermatologic autoimmune disease that affects adults and children. Roflumilast 0.3% cream is currently the only topical phosphodiesterase 4 inhibitor indicated for the treatment of plaque psoriasis in patients 12 years or older. PHARMACODYNAMICS AND PHARMACOKINETICS: Roflumilast inhibits phosphodiesterase 4 inhibitor enzyme leading to the accumulation of cyclic adenosine monophosphate, which suppresses the inflammatory mediators interferon-γ and tumor necrosis factor-α. Roflumilast, applied once daily, reaches steady state by day 15 and has a half life of approximately 4 days in adults. Roflumilast undergoes extensive hepatic metabolism by cytochrome P450 enzymes and conjugation. Roflumilast is 99% bound to plasma proteins. CLINICAL TRIALS: Roflumilast efficacy and safety were evaluated in the DERMIS-1 and DERMIS-2 clinical trials. These identically designed, double-blind, vehicle-controlled phase 3 trials randomized 881 patients to roflumilast 0.3% cream or vehicle, applied once daily for 8 weeks. In DERMIS-1, the Investigator Global Assessment success rate was 42.4% with roflumilast 0.3% cream compared with 6.1% with the vehicle (32.3%-46.9%; P <0.001). Similarly, in DERMIS-2, the Investigator Global Assessment success rate was 37.5% with roflumilast 0.3% cream compared with 6.9% with the vehicle (20.8%-36.9%; P <0.001). Of 881 participants, 1% discontinued treatment with roflumilast cream due to adverse reactions compared with 1.3% treated with vehicle. Urticaria at the application site (0.3%) was the most common adverse reaction that led to discontinuation of roflumilast. THERAPEUTIC ADVANCE: To date, topical corticosteroids are the most commonly used agents to treat mild plaque psoriasis. Sensitive areas are often challenging to treat with existing topical therapy, including corticosteroids. Topical roflumilast has shown to be effective in treating sensitive areas, including skin folds, and may be an alternative to systemic therapy for some patients. The Food and Drug Administration approved topical roflumilast for the treatment of plaque psoriasis, including intertriginous areas, for patients 12 years or older.

Venous thromboembolism prophylaxis in medically ill patients: a mixed treatment comparison meta-analysis.

The American College of Chest Physicians guidelines recommend unfractionated heparin (UFH), low molecular weight heparins (LMWHs) or fondaparinux for prevention of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), in medically-ill patients. Direct oral anticoagulants (DOACs) have been evaluated relative to enoxaparin for VTE prophylaxis though head-to-head comparisons of these agents are lacking. Therefore, we conducted a mixed treatment comparisons meta-analysis to evaluate the safety and efficacy of established treatments and DOACs for VTE prophylaxis in medically-ill patients. A comprehensive literature search was conducted to identify randomized trials evaluating UFH, LMWHs or DOACS for the prevention of VTE in medically ill patients. Articles were retrieved and cross-referenced for additional trials, evaluated and entered into ADDIS (version 1.16.6) to generate direct and indirect treatment comparisons for VTE, DVT, PE, death from any cause, and bleeding. Ten articles were included and eight anticoagulants were evaluated in a treatment network representing data on 28,382 patients. We found each treatment had similar efficacy in preventing VTE, DVT, PE, death from any cause and each had similar risk of minor and major bleeding. Overall, placebo was associated with more VTE and DVT events compared to LMWHs and DOACs. We found that UFH, LMWHs and DOACs are comparable in preventing VTE, DVT, PE, and death from any cause and in association with minor and major bleeding. Anticoagulant selection for VTE prophylaxis in medically-ill patients should be individualized by patient characteristics, risks and preferences along with specific pharmacokinetic and pharmacodynamic considerations.

Exploring the effect of complex patients on care delivery tasks.

PURPOSE: The needs of complex patients with chronic conditions can be unpredictable and can strain resources. Exploring how tasks vary for different patients, particularly those with complex needs, can yield insights about designing better processes in healthcare. The purpose of this paper is to explore the tasks required to manage complex patients in an anticoagulation therapy context. DESIGN/METHODOLOGY/APPROACH: The authors analyzed interviews with 55 staff in six anticoagulation clinics using the Systems Engineering Initiative for Patient Safety (SEIPS) work system framework. The authors qualitatively described complex patients and their effects on care delivery. FINDINGS: Data analysis highlighted how identifying complex patients and their effect on tasks and organization, and the interactions between them was important. Managing complex patients required similar tasks as non-complex patients, but with greater frequency or more intensity and several additional tasks. After complex patients and associated patient interaction and care tasks were identified, a work system perspective was applied to explore how such tasks are integrated within clinics and the resulting implications for resource allocation. PRACTICAL IMPLICATIONS: The authors present a complex patient management framework to guide workflow design in specialty clinics, to better support high quality, effective, efficient and safe healthcare. ORIGINALITY/VALUE: The complex patient framework presented here, based on the SEIPS framework, suggests a more formal and integrated analysis be completed to provide better support for appropriate resource allocation and care coordination.

A polypill for all? Critical review of the polypill literature for primary prevention of cardiovascular disease and stroke.

OBJECTIVE: To evaluate the efficacy and safety of the polypill for prevention of cardiovascular disease (CVD) and stroke and to present literature related to the polypill components (statin, aspirin, antihypertensive) for primary prevention of CVD and stroke. DATA SOURCES: A literature search was conducted in MEDLINE (1948-January 2011) and EMBASE (1974-January 2011) using the terms polypill and Polycap. When limited to clinical trials, systematic reviews, or meta-analyses, 7 studies were identified. Bibliographies of pertinent review articles and studies were scanned for additional references. A similar search was conducted to identify literature related to the use of polypill components for primary prevention of CVD and stroke. STUDY SELECTION AND DATA EXTRACTION: Studies that evaluated the hypothetical benefits of a polypill and controlled trials that assessed a formulation of the polypill related to prevention of CVD and stroke were included. Studies were assessed for efficacy, safety, drug interactions, and clinical pharmacokinetics. DATA SYNTHESIS: An initial study to predict benefit estimated that a hypothetical polypill would reduce diastolic blood pressure by 11 mm Hg and low-density lipoprotein cholesterol (LDL-C) by 70 mg/dL, thus reducing the relative risks of CVD and stroke by 88% and 80%, respectively. One clinical trial in patients at low risk for CVD and stroke found that diastolic blood pressure was reduced by 1.6 mm Hg and LDL-C was reduced by 17.7 mg/dL, correlating with 44% and 21% reduction in the relative risks of CVD and stroke, respectively. Studies in higher risk patients reported reductions in systolic blood pressure of up to 28.8 mm Hg and in LDL-C of up to 54 mg/dL, correlating with 62% and 60% relative reduction in risks of CVD and stroke, respectively. CONCLUSIONS: Polypill study results have been more modest than originally theorized. However, results show promise in patients at higher risk for CVD and stroke.

Technological resources and personnel costs required to implement an automated alert system for ambulatory physicians when patients are discharged from hospitals to home.

BACKGROUND: With the adoption of electronic medical records by medical group practices, there are opportunities to improve the quality of care for patients discharged from hospitals. However, there is little guidance for medical groups outside integrated hospital systems to automate the flow of patient information during transitions in care. OBJECTIVE: To describe the technological resources, expertise and time needed to develop an automated system providing information to ambulatory physicians when their patients are discharged from hospitals to home. DEVELOPMENT: Within a medical group practice, we developed an automated alert system that provides notification of discharges, reminders of the need for follow-up visits, drugs added during inpatient stays, and recommendations for laboratory monitoring of high-risk drugs. We tracked components of the information system required and the time spent by team members. We used USA national averages of hourly wages to estimate personnel costs. APPLICATION: Critical components of the information system are notifications of hospital discharges through an admission, discharge and transfer registration (ADT) interface, linkage to the group's scheduling system, access to information on pharmacy dispensing and lab tests, and an interface engine. Total personnel cost was $76,314. Nearly half (47%) was for 614 hours by physicians who developed content, provided overall project management, and reviewed alerts to ensure that only 'actionable' alerts would be sent. CONCLUSION: Implementing a system to provide information about hospital discharges requires strong internal informatics expertise, cooperation between facilities and ambulatory providers, development of electronic linkages, and extensive commitment of physician time.

Effect of a Multifaceted Clinical Pharmacist Intervention on Medication Safety After Hospitalization in Persons Prescribed High-risk Medications: A Randomized Clinical Trial.

Importance: The National Action Plan for Adverse Drug Event (ADE) Prevention identified 3 high-priority, high-risk drug classes as targets for reducing the risk of drug-related injuries: anticoagulants, diabetes agents, and opioids. Objective: To determine whether a multifaceted clinical pharmacist intervention improves medication safety for patients who are discharged from the hospital and prescribed medications within 1 or more of these high-risk drug classes. Design, Setting, and Participants: This randomized clinical trial was conducted at a large multidisciplinary group practice in Massachusetts and included patients 50 years or older who were discharged from the hospital and prescribed at least 1 high-risk medication. Participants were enrolled into the trial from June 2016 through September 2018. Interventions: The pharmacist-directed intervention included an in-home assessment by a clinical pharmacist, evidence-based educational resources, communication with the primary care team, and telephone follow-up. Participants in the control group were provided educational materials via mail. Main Outcomes and Measures: The study assessed 2 outcomes over a 45-day posthospital discharge period: (1) adverse drug-related incidents and (2) a subset defined as clinically important medication errors, which included preventable or ameliorable ADEs and potential ADEs (ie, medication-related errors that may not yet have caused injury to a patient, but have the potential to cause future harm if not addressed). Clinically important medication errors were the primary study outcome. Results: There were 361 participants (mean [SD] age, 68.7 [9.3] years; 177 women [49.0%]; 319 White [88.4%] and 8 Black individuals [2.2%]). Of these, 180 (49.9%) were randomly assigned to the intervention group and 181 (50.1%) to the control group. Among all participants, 100 (27.7%) experienced 1 or more adverse drug-related incidents, and 65 (18%) experienced 1 or more clinically important medication errors. There were 81 adverse drug-related incidents identified in the intervention group and 72 in the control group. There were 44 clinically important medication errors in the intervention group and 45 in the control group. The intervention did not significantly alter the per-patient rate of adverse drug-related incidents (unadjusted incidence rate ratio, 1.13; 95% CI, 0.83-1.56) or clinically important medication errors (unadjusted incidence rate ratio, 0.99; 95% CI, 0.65-1.49). Conclusions and Relevance: In this randomized clinical trial, there was not an observed lower rate of adverse drug-related incidents or clinically important medication errors during the posthospitalization period that was associated with a clinical pharmacist intervention. However, there were study recruitment challenges and lower than expected numbers of events among the study population. Trial Registration: ClinicalTrials.gov Identifier: NCT02781662.

In the Eye of the Storm: The Role of the Pharmacist in Medication Safety during the COVID-19 Pandemic at an Urban Teaching Hospital.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease (COVID-19) pandemic, has challenged practitioners with complex clinical scenarios as well as conflicting and scarce data to support treatment strategies. The pandemic has also placed strains on institutions due to drug shortages, alterations in medication use processes, economic losses, and staff exposure to the virus. This article provides pharmacist-led suggestions and strategies to various case questions, describing some of the challenges faced by practitioners at an urban teaching hospital during the COVID-19 pandemic. The strategies suggested can be explored at other institutions.

Meta-analysis of venous thromboembolism prophylaxis in medically Ill patients.

BACKGROUND: Venous thromboembolism (VTE) prophylaxis in medically ill patients has received a level 1A recommendation in previously published clinical guidelines. Pharmacologic prophylaxis for VTE includes unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), and fondaparinux. Few direct comparisons between anticoagulants exist in medically ill patients. OBJECTIVE: This meta-analysis was conducted to assess UFH and LMWH (including the selective factor Xa inhibitor fondaparinux) in the reduction of in-hospital VTE in unselected medically ill patients. METHODS: We searched MEDLINE, EMBASE, and the Cochrane Controlled Trials Registry databases from January 1981 through September 2007 (English language) for randomized controlled trials using the following terms: dalteparin, enoxaparin, fondaparinux, nadroparin, and heparin. References of included articles and key review papers for additional studies were also searched. Data from studies were included in the analysis if the studies included medically ill patients with risk factors for VTE who had been followed up for 7 to 21 days. RESULTS: A total of 12,391 patients (of whom 8357 were in placebo-controlled trials) from 9 studies were included. Mean age for the entire cohort was 72.8 years; mean (SD) body mass index, 25.6 kg/m2; and mean (SD) actual body weight, 68.2 kg. Deep vein thrombosis (DVT) was significantly reduced with the addition of an LMWH compared with placebo (odds ratio [OR], 0.60; 95% CI, 0.47-0.75; P < or = 0.001), but rates of DVT were similar when comparing LMWH with UFH (OR, 0.92; 95% CI, 0.56-1.52). No significant differences in pulmonary embolism (PE) or death were found among the UFH, LMWH, and placebo groups. LMWH was associated with a significant increased risk for minor bleeding compared with placebo (OR, 1.64; 95% CI, 1.18-2.29; P = 0.003). However, no significant difference was found between LMWH and UFH (OR, 0.68; 95% CI, 0.27-1.70). Major bleeding events were similar among all groups: LMWH/fondaparinux versus placebo, OR, 1.65 (95% CI, 0.8-3.4); LMWH/fondaparinux versus UFH, OR, 0.69 (95% CI, 0.29-1.68); LMWH/fondaparinux versus UFH or placebo, OR, 1.16 (95% CI, 0.66-2.04). CONCLUSIONS: This analysis suggests that VTE prophylaxis with an LMWH (including fondaparinux) or UFH is effective in reducing the rate of DVT, but this benefit did not extend to enhanced protection against PE. Additionally, LMWH and UFH had similar bleeding outcomes.

A Pilot Health Information Technology-Based Effort to Increase the Quality of Transitions From Skilled Nursing Facility to Home: Compelling Evidence of High Rate of Adverse Outcomes.

OBJECTIVES: Older adults are often transferred from hospitals to skilled nursing facilities (SNFs) for post-acute care. Patients may be at risk for adverse outcomes after SNF discharges, but little research has focused on this period. DESIGN: Assessment of the feasibility of a transitional care intervention based on a combination of manual information transmission and health information technology to provide automated alert messages to primary care physicians and staff; pre-post analysis to assess potential impact. SETTING: A multispecialty group practice. PARTICIPANTS: Adults aged 65 and older, discharged from SNFs to home; comparison group drawn from SNF discharges during the previous 1.5 years, matched on facility, patient age, and sex. MEASUREMENTS: For the pre-post analysis, we tracked rehospitalization within 30 days after discharge and adverse drug events within 45 days. RESULTS: The intervention was developed and implemented with manual transmission of information between 8 SNFs and the group practice followed by entry into the electronic health record. The process required a 5-day delay during which a large portion of the adverse events occurred. Over a 1-year period, automated alert messages were delivered to physicians and staff for the 313 eligible patients discharged from the 8 SNFs to home. We compared outcomes to those of individually matched discharges from the previous 1.5 years and found similar percentages with 30-day rehospitalizations (31% vs 30%, adjusted HR 1.06, 95% CI 0.80-1.4). Within the adverse drug event (ADE) study, 30% of the discharges during the intervention period and 30% of matched discharges had ADEs within 45 days. CONCLUSION: Older adults discharged from SNFs are at high risk of adverse outcomes immediately following discharge. Simply providing alerts to outpatient physicians, especially if delivered multiple days after discharge, is unlikely to have any impact on reducing these rates.

Research fellowship programs as a pathway for training independent clinical pharmacy scientists.

The American College of Clinical Pharmacy (ACCP) Research Affairs Committee published a commentary in 2013 on training clinical pharmacy scientists in the context of changes in economic, professional, political, and research environments. The commentary centered on the opportunities for pharmacists in clinical/translational research including strategies for ACCP, colleges of pharmacy, and the profession to increase the number and impact of clinical pharmacy scientists. A postdoctoral fellowship is cited as a current training pathway, capable of producing independent and productive pharmacy researchers. However, a decline in the number of programs, decreased funding availability, and variability in fellowship program activities and research focus have brought into question the relevance of this research training pathway to meet demand and opportunities. In response to these points, this commentary examines the state of research fellowship training including the current ACCP research fellowship review process, the need for standardization of research fellowship programs, and strategies to strengthen and promote research fellowships as relevant researcher training pathways.

Dissemination of Evidence-Based Antipsychotic Prescribing Guidelines to Nursing Homes: A Cluster Randomized Trial.

OBJECTIVES: To evaluate the effectiveness of efforts to translate and disseminate evidence-based guidelines about atypical antipsychotic use to nursing homes (NHs). DESIGN: Three-arm, cluster randomized trial. SETTING: NHs. PARTICIPANTS: NHs in the state of Connecticut. MEASUREMENTS: Evidence-based guidelines for atypical antipsychotic prescribing were translated into a toolkit targeting NH stakeholders, and 42 NHs were recruited and randomized to one of three toolkit dissemination strategies: mailed toolkit delivery (minimal intensity); mailed toolkit delivery with quarterly audit and feedback reports about facility-level antipsychotic prescribing (moderate intensity); and in-person toolkit delivery with academic detailing, on-site behavioral management training, and quarterly audit and feedback reports (high intensity). Outcomes were evaluated using the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework. RESULTS: Toolkit awareness of 30% (7/23) of leadership of low-intensity NHs, 54% (19/35) of moderate-intensity NHs, and 82% (18/22) of high-intensity NHs reflected adoption and implementation of the intervention. Highest levels of use and knowledge among direct care staff were reported in high-intensity NHs. Antipsychotic prescribing levels declined during the study period, but there were no statistically significant differences between study arms or from secular trends. CONCLUSION: RE-AIM indicators suggest some success in disseminating the toolkit and differences in reach, adoption, and implementation according to dissemination strategy but no measurable effect on antipsychotic prescribing trends. Further dissemination to external stakeholders such as psychiatry consultants and hospitals may be needed to influence antipsychotic prescribing for NH residents.

Use of atypical antipsychotics in nursing homes and pharmaceutical marketing.

OBJECTIVES: To describe the current extent and type of pharmaceutical marketing in nursing homes (NHs) in one state and to provide preliminary evidence for the potential influence of pharmaceutical marketing on the use of atypical antipsychotics in NHs. DESIGN: Nested mixed-methods, cross-sectional study of NHs in a cluster randomized trial. SETTING: Forty-one NHs in Connecticut. PARTICIPANTS: NH administrators, directors of nursing, and medical directors (n = 93, response rate 75.6%). MEASUREMENTS: Quantitative data, including prescription drug dispensing data (September 2009-August 2010) linked with Nursing Home Compare data (April 2011), were used to determine facility-level prevalence of atypical antipsychotic use, facility-level characteristics, NH staffing, and NH quality. Qualitative data, including semistructured interviews and surveys of NH leaders conducted in the first quarter of 2011, were used to determine encounters with pharmaceutical marketing. RESULTS: Leadership at 46.3% of NHs (n = 19) reported pharmaceutical marketing encounters, consisting of educational training, written and Internet-based materials, and sponsored training. No association was detected between level of atypical antipsychotic prescribing and reports of any pharmaceutical marketing by at least one NH leader. CONCLUSION: NH leaders frequently encounter pharmaceutical marketing through a variety of ways, although the impact on atypical antipsychotic prescribing is unclear.

Evaluation of oral anticoagulants for the extended treatment of venous thromboembolism using a mixed-treatment comparison, meta-analytic approach.

PURPOSE: Target-specific oral anticoagulants (apixaban, rivaroxaban, and dabigatran) are widely available for the treatment of venous thromboembolism (VTE). Although analyses comparing these agents to placebo or warfarin exist, direct comparisons of these agents for extended VTE treatment have not been conducted. Therefore, this network meta-analysis aimed to evaluate the efficacy and tolerability of VKA and target-specific oral anticoagulants for extended VTE treatment using a mixed-treatment comparison, meta-analytic approach. METHODS: A comprehensive literature search of EMBASE and MEDLINE was conducted to identify relevant randomized, controlled trials published in English between 1960 and November 2013. Eligible studies investigated the extended use (≥6 months) of oral anticoagulants (apixaban, dabigatran, rivaroxaban, and/or warfarin [conventional or low dose]) and placebo in patients with confirmed VTE. Search terms included extension or extended treatment or therapy, venous thromboembolism (or VTE), deep vein thrombosis (or DVT), pulmonary embolism (or PE), and anticoagulant or anticoagulant agent. Key articles were cross-referenced for additional studies. The efficacy end points evaluated were recurrent VTE or death from any cause, DVT, and nonfatal pulmonary embolism PE. Tolerability end points included major bleeding and nonmajor or clinically relevant bleeding. The data were screened, evaluated, and entered into statistical software to generate direct and indirect comparisons of the various anticoagulants across each study. The data are reported as rate ratios and 95% credible intervals. FINDINGS: Ten trials were analyzed and aggregated, representing data from >14,000 patients. With respect to efficacy end points, no statistically significant between-treatment differences in the composite end point of VTE or death, nonfatal PE, or DVT were found. Major bleeding was significantly greater with warfarin versus apixaban (rate ratio, 4.24; credible interval, 1.28-25.0), and the risk for major bleeding varied somewhat with warfarin and greatly with rivaroxaban. The assessment of nonmajor or clinically relevant bleeding did not identify any meaningful differences between these agents. IMPLICATIONS: The majority of the data represented in this study were derived from noninferiority trials. In the present meta-analysis, efficacy end points in the extended treatment of VTE with apixaban, dabigatran, rivaroxaban, warfarin (conventional and low dose), and placebo were not significantly different. Elevated bleeding risks were identified with rivaroxaban and warfarin; however, the wide credible intervals with rivaroxaban prevent the interpretation of these increased risks.

An electronic health record-based intervention to increase follow-up office visits and decrease rehospitalization in older adults.

OBJECTIVES: To assess the effect of an electronic health record-based transitional care intervention involving automated alerts to primary care providers and staff when older adults were discharged from the hospital. DESIGN: Randomized controlled trial. SETTING: Large multispecialty group practice. PARTICIPANTS: Individuals aged 65 and older discharged from hospital to home. INTERVENTION: In addition to notifying primary care providers about the individual's recent discharge, the system provided information about new drugs added during the inpatient stay, warnings about drug-drug interactions, recommendations for dose changes and laboratory monitoring of high-risk medications, and alerts to the primary care provider's support staff to schedule a posthospitalization office visit. MEASUREMENTS: An outpatient office visit with a primary care provider after discharge and rehospitalization within 30 days after discharge. RESULTS: Of the 1,870 discharges in the intervention group, 27.7% had an office visit with a primary care provider within 7 days of discharge. Of the 1,791 discharges in the control group, 28.3% had an office visit with a primary care provider within 7 days of discharge. In the intervention group, 18.8% experienced a rehospitalization within the 30-day period after discharge, compared with 19.9% in the control group. The hazard ratio for an office visit with a primary care physician did not significantly differ between the intervention and control groups. The hazard ratio for rehospitalization in the 30-day period after hospital discharge in the intervention versus the control group was 0.94 (95% confidence interval = 0.81-1.1). CONCLUSION: This electronic health record-based intervention did not have a significant effect on the timeliness of office visits to primary care providers after hospitalization or risk of rehospitalization.

Evaluation of antiplatelet agents for secondary prevention of stroke using mixed treatment comparison meta-analysis.

BACKGROUND: The current guidelines recommend various antiplatelet agents used alone or in combination for secondary prevention of noncardioembolic stroke. OBJECTIVE: The purpose of this study was to conduct a mixed treatment comparison meta-analysis to determine which antiplatelet or combination of antiplatelet agents is most efficacious and tolerable in patients with prior stroke. METHODS: A comprehensive literature search was conducted in MEDLINE (1945 through March 2012), EMBASE (1974 through March 2012), and the Cochrane Controlled Trials Registry (1975 through April 2012) to identify randomized trials evaluating the role of various antiplatelet agents and combinations for the secondary prevention of stroke. Key articles were cross-referenced for additional studies. Data were screened and evaluated to generate direct and indirect comparisons for recurrent stroke and overall hemorrhagic events. Data were reported as rate ratios (RRs) and 95% CIs. RESULTS: A total of 24 articles were included in the analysis. Eleven antiplatelet regimens were compared in >88,000 patients. The combination of acetylsalicylic acid (ASA) plus dipyridamole (DP) was more protective against recurrent stroke than ASA alone (RR = 0.78; 95% CI, 0.64-0.93), and no differences were found in all other direct and indirect comparisons with active treatment. ASA plus DP was associated with more overall hemorrhagic events than DP (RR = 1.83; 95% CI, 1.17-2.81), cilostazol (RR = 2.12; 95% CI, 1.21-3.48), and triflusal (RR = 1.67; 95% CI, 1.05-2.78) but fewer events than the combination of ASA plus clopidogrel (RR = 0.38; 95% CI, 0.25-0.56). The combination of ASA plus clopidogrel was associated with an excess of overall hemorrhagic events compared with clopidogrel (RR = 2.81; 95% CI, 1.96-4.10), cilostazol (RR = 5.56; 95% CI, 3.03-9.66), DP (RR = 4.78; 95% CI, 2.80-8.21), sarpogrelate (RR = 3.59; 95% CI, 1.96-6.45), terutroban (RR = 2.13; 95% CI, 1.21-3.61), ticlopidine (RR = 2.80; 95% CI, 1.69-5.00), and triflusal (RR = 4.36; 95% CI, 2.62-7.81). CONCLUSION: We found that ASA plus DP was more protective than ASA alone for preventing recurrent stroke; however, no difference was found between most direct and indirect comparisons of antiplatelet agents and combinations. More overall hemorrhagic events seemed to occur with the combination of ASA and clopidogrel than with other treatments. Selection of antiplatelet therapy for the secondary prevention of stroke must be individualized according to patient comorbidities, including risk of stroke recurrence and bleeding.

Mixed treatment comparison meta-analysis of aspirin, warfarin, and new anticoagulants for stroke prevention in patients with nonvalvular atrial fibrillation.

BACKGROUND: Warfarin and aspirin are used to prevent stroke in patients with atrial fibrillation (AF). There are inherent challenges with both treatments, including variable and inconsistent benefit and increased bleeding risks. The availability of new anticoagulants offers some alternatives. OBJECTIVE: A mixed treatment comparison meta-analysis to evaluate direct and indirect treatment data including aspirin, warfarin apixaban, dabigatran, edoxaban, and rivaroxaban for the prevention of primary or secondary stroke in patients with AF. METHODS: A comprehensive, systematic literature search was conducted to identify randomized trials comparing aspirin, warfarin, apixaban, dabigatran, edoxaban, and rivaroxaban in patients with AF requiring treatment for stroke prevention. Open-label and blinded designs were included if they evaluated any stroke or any bleeding event. Data on stroke and bleeding events were abstracted, verified, evaluated, scored, and entered into Aggregate Data Drug Information System version 1.16 to generate a mixed treatment comparison meta-analysis. Direct and indirect comparisons were evaluated, and we looked for inconsistency in closed loop structures. Data are reported as rate ratios with 95% credible intervals. In addition, we reviewed variance statistics and explored variance with node-splitting models. RESULTS: Our literature search yielded 30 articles, 21 of which were included. All treatments except aspirin reduced the risk of any stroke compared with placebo. Warfarin (0.43 [0.33-0.57]), apixaban (0.37 [0.27-0.54]), dabigatran (0.34 [0.21-0.57]), rivaroxaban (0.36 [0.22-0.60]), and aspirin with clopidogrel (0.73 [0.53-0.99]) were more protective than aspirin alone. Warfarin and the new anticoagulants were similar in the reduction of stroke, vascular death, and mortality. There was no difference in major bleeding between any treatment group. There were more nonmajor bleeding events when comparing warfarin and apixaban (1.83 [1.05-4.03]); no other differences between warfarin and the other new anticoagulants were found. CONCLUSIONS: This mixed treatment comparison meta-analysis found similarity between warfarin and the new anticoagulants with the exception of one comparison, in which warfarin was associated with more non-major bleeding than apixaban. Thus, the new anticoagulants are therapeutically comparable when warfarin is inappropriate.

Adverse drug events after hospital discharge in older adults: types, severity, and involvement of Beers Criteria Medications.

OBJECTIVES: To characterize adverse drug events (ADEs) occurring within the high-risk 45-day period after hospitalization in older adults. DESIGN: Clinical pharmacists reviewed the ambulatory records of 1,000 consecutive discharges. SETTING: A large multispecialty group practice closely aligned with a Massachusetts-based health plan. PARTICIPANTS: Hospitalized individuals aged 65 and older discharged home. MEASUREMENTS: Possible drug-related incidents occurring during the 45-day period after hospitalization were identified and presented to a pair of physician-reviewers who classified incidents as to whether an ADE was present, whether the event was preventable, and the severity of the event. Medications implicated in ADEs were further characterized according to their inclusion in the 2012 Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. RESULTS: At least one ADE was identified during the 45-day period in 18.7% (n = 187) of the 1,000 discharges. Of the 242 ADEs identified, 35% (n = 84) were deemed preventable, of which 32% (n = 27) were characterized as serious, and 5% (n = 4) as life threatening. More than half of all ADEs occurred within the first 14 days after hospitalization. The percentage of ADEs in which Beers Criteria medications were implicated was 16.5% (n = 40). Beers criteria medications with both a high quality of evidence and strong strength of recommendation were implicated in 6.6% (n = 16) of the ADEs. CONCLUSION: ADEs are common and often preventable in older adults after hospital discharge, underscoring the need to address medication safety during this high-risk period in this vulnerable population. Beers criteria medications played a small role in these events, suggesting that efforts to improve the quality and safety of medication use during this critical transition period must extend beyond a singular focus on Beers criteria medications.