Mitapivat: A Quinolone Sulfonamide to Manage Hemolytic Anemia in Adults With Pyruvate Kinase Deficiency.

BACKGROUND: Pyruvate kinase (PK) deficiency is a rare enzyme-linked glycolytic defect resulting in mild-to-severe chronic persistent erythrocyte hemolysis. The disease is an autosomal recessive trait caused by mutations in the PK liver and red blood cell gene characterized by insufficient erythrocyte PK activity. PK deficiency is most diagnosed in persons of northern European descent and managed with packed red blood cell transfusions, chelation, and splenectomy with cholecystectomy. Mitapivat is the first approved therapy indicated for hemolytic anemia in adults with PK deficiency with the potential for delaying splenectomy in mild-moderate disease. MECHANISM OF ACTION, PHARMACODYNAMICS, AND PHARMACOKINETICS: Mitapivat is a PK activator that acts by allosterically binding to the PK tetramer and increases PK activity. The red blood cell form of PK is mutated in PK deficiency, which leads to reduced adenosine triphosphate, shortened red blood cell lifespan, and chronic hemolysis. The half-life of elimination is 3-5 hours, with 73% bioavailability, 98% plasma protein binding, and a median duration of response of 7 months. CLINICAL TRIALS: Mitapivat has been investigated through various clinical trials for different therapeutic indications. Pivotal trials that serve the primary focus throughout this article are ACTIVATE, ACTIVATE-T, and RISE. ACTIVATE is a phase 3, randomized, double-blind, placebo-controlled study that evaluated the efficacy and safety of mitapivat in adult patients who were not receiving regular blood transfusions. Contrarily, ACTIVATE-T explored the safety and efficacy of mitapivat in adults with PK deficiency who received regular blood transfusions. Both trials demonstrated favorable use of mitapivat in PK deficiency. Focusing on another indication, the ongoing RISE trial investigates the optimal dosage of mitapivat in sickle cell disease. THERAPEUTIC ADVANCE: Mitapivat is an appropriate treatment for adults with PK deficiency requiring transfusions and may be considered for patients with symptomatic anemia who do not require transfusions and/or PK deficiency with compensated hemolysis without overt anemia.

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.

Cost savings impact of a pharmacist-initiated teleservice program for Medicare Part D reviews.

OBJECTIVES: To (a) determine potential cost savings of a pharmacy outreach teleservice program conducting Medicare Part D plan reviews for a large population of beneficiaries allowing for comparison of multiple preferences; and (b) explore client demographic comparisons, plan features, and stratification by cost and number of medications. METHODS: Retrospective cohort evaluation of a Medicare D review service during open enrollment period (October 15 to December 7, 2012). Reviews were conducted at a university-based pharmacy outreach program in Massachusetts and completed by pharmacists (17%), case managers (52%), and students (31%). Recommendations were created by entering medication regimens into the Medicare.gov plan finder, and factors including deductible, premium, and copayment or coinsurance, formulary restrictions, secondary assistance, and annual cost were considered. A comparison of the overall cost of the client's 2012 plan in 2013 with that of a lower-cost plan in the 2013 benefit year determined potential cost savings. RESULTS: Demographic data were available for 1062 individuals, with the majority being women (66%), an overall mean age of 73 years, and most living in a single household. Clients (75%) were taking 5 or more medications. Lower-cost plans were recommended for 61% of clients with a median cost savings valued at $538 per member, per year. Cost was the leading consideration for plan change (87.4%), followed by deductible (32.7%) and premium (30.1%). Cost savings were analyzed by evaluating current plan versus alternate plan by sex, age, client type (repeat vs. referred vs. new), and according to number of medications. Lower-cost plans were identified for 75% of new members. Individuals taking 0-14 medications had a cost savings of approximately $833 per client per year. CONCLUSION: Teleservice pharmacy outreach programs create value by identifying therapeutically comparable alternative plans and reducing plan spending while efficiently consulting for a large number of Medicare Part D beneficiaries statewide.

Acute Pancreatitis Associated With Antipsychotic Medication: Evaluation of Clinical Features, Treatment, and Polypharmacy in a Series of Cases.

BACKGROUND: Antipsychotic-associated acute pancreatitis presents like pancreatitis from other causes, requiring clinical judgment, tests, and decision support to establish the diagnosis. Many new cases of atypical antipsychotic pancreatitis have been established, and current decision supports are out of date as antipsychotic polypharmacy is being recognized. Given the population frequency of psychosis and frequency of antipsychotic prescribing, we reviewed published cases summarizing common clinical findings and antipsychotics associated with acute pancreatitis to updating earlier decision support. METHODS: Case reports of antipsychotic pancreatitis from 1990 to 2015 were reviewed and abstracted by independent reviewers. Demographic, clinical features, management, and Naranjo and probability scores were abstracted and reviewed for associations. Appropriate statistical tests were selected for normally and non-normally distributed data. RESULTS: We summarized 41 cases of acute pancreatitis associated with antipsychotics, and cases were younger men (59%) (mean age, 39 years). Alcohol, diabetes, and previous lithiasis appeared in 27%; polypharmacy was associated with 53% of cases, and 80% had concomitant use of other medication linked to pancreatitis.The median lipase, amylase, and alkaline phosphate during acute presentation were 1210 IU/L (range, 243-5482 IU/L), 492 IU/L (range, 3-2916 IU/L), and 152 IU/L (range, 119-367 IU/L), respectively. Median exposure to antipsychotics were 49 days (range, 5-3,650 days); most were mild (63%, n = 26), several severe (27%, n = 11), and few fatal (10%, n = 4). DISCUSSION: We identified 41 reports of antipsychotic-related acute pancreatitis, many associated with antipsychotic polypharmacy. Olanzapine, risperidone, quetiapine, aripiprazole, and ziprasidone are associated with acute pancreatitis and often in combination with mood stabilizers.

Pharmacist telehealth in an underserved urban population with type 2 diabetes mellitus.

BACKGROUND: During the pre-vaccine months of the COVID-19 pandemic, pharmacists providing comprehensive medication management to underserved patients with type 2 diabetes mellitus at an urban Federally Qualified Healthcare Center shifted to telephone-based telehealth. OBJECTIVES: This retrospective, observational cohort study evaluated the effectiveness of clinical pharmacist telehealth while identifying associations between patient characteristics and efficacy measures. METHODS: Patients with uncontrolled type 2 diabetes (hemoglobin A1c (HbA1c) ≥ 8%) with a clinical pharmacist visit between April 1 and August 31, 2020, were included. Telehealth effectiveness was measured by the proportions of: 1) patients reached, 2) appointments completed, and 3) the median change in HbA1c from baseline. Interventions by the clinical pharmacist were analyzed as a secondary outcome. RESULTS: There were 181 patients scheduled and 172 (95%) of those patients kept at least one appointment. Of the 667 appointments scheduled, 73% were kept. Median HbA1c was reduced from 10.2% to 9.2% over 5 months of follow-up, and 24.6% of patients achieved a HbA1c < 8% (n = 138, p < 0.0001 for each). Greater HbA1c changes were associated with higher baseline blood glucose (p = 0.01), higher baseline HbA1c (p < 0.0001), non-insulin medications at baseline (p = 0.007) and among those with more kept visits (p = 0.03). The healthcare quality impact of interventions during each appointment was favorable; 83.3% brought care to a higher standard, 1.9% averted major organ dysfunction and 0.4% prevented death. CONCLUSIONS: Clinical pharmacist telehealth was effective for providing patient-centered diabetes care when in-person office visits were not an option.

Partnering for health: collaborative leadership between a community health center and the YWCA central Massachusetts.

BACKGROUND: A collaborative partnership among community-based organizations (CBOs)-a community-health center, a YWCA, and 2 academic health centers-developed and implemented open access to physical activity for health center patients. OBJECTIVE: To describe partnership approach taken by 2 CBOs; determine staffs' views of this unique partnership, highlight aspects of the partnership that contributed to its success, identify challenges and mechanisms for overcoming them, and note lessons learned. Assess health center patients' use of YWCA facility. METHODS: Usage data were obtained from YWCA records. Staff were interviewed using primarily open-ended questions. Inductive approach was used to analyze qualitative data. RESULTS: The approach to partnership was largely organic, without formal working documents; nevertheless, the partnership reflected the organizations' missions. Over 4 years, 1134 health center patients made more than 23 000 visits to the YWCA. Responses of health center staff and provider interviewees about partnership processes sorted into the following categories: partnership description and results, partnership benefits, challenges, lessons learned, and advice to other CBOs. YWCA staff interviewee responses reflected the categories: staffing, clientele, and public face. Comments also included challenges, lessons learned, and advice to other YWCAs. CONCLUSIONS: This partnership achieved notable successes largely because (a) it formed to serve a specific purpose that met both agencies' goals, (b) leaders made sustained commitments, and (c) it managed conflict. The partnership has taken on new projects over time; new ideas for improving access and service to underserved patients continue to emerge. Interorganizational trust and allegiance have been key to addressing challenges; nevertheless, the organic nature of the partnership's origins and the challenges of success have meant that the partnership has restructured its agreement and, to avoid being overwhelmed, limited new patient use.

Correlation of inhibition of platelet aggregation after clopidogrel with post discharge bleeding events: assessment by different bleeding classifications.

AIMS: To correlate inhibition of platelet aggregation (IPA) with bleeding events assessed by TIMI, GUSTO, and BleedScore scales in a large cohort of patients with coronary artery disease (CAD) and ischaemic stroke (IS) treated with chronic low-dose aspirin plus clopidogrel. Data from recent trials and registries suggest a link between increased risk of bleeding and cardiovascular mortality. However, the potential association of bleeding risk and IPA is not established. It may play a critical role for the safety of more aggressive platelet inhibition or/and individual tailoring of antiplatelet strategies. METHODS AND RESULTS: Secondary post hoc analyses of 5 microM ADP-induced IPA and bleeding complications assessed by TIMI, GUSTO, and BleedScore scales in a combined data set consisting of patients with documented CAD (n = 246) and previous IS (n = 117). Demographic characteristics differ substantially depending on the underlying vascular disease; however, IPA and bleeding risks were similar between CAD and IS. All three bleeding scales adequately captured serious haemorrhagic events, where the TIMI scale was the most exclusive, whereas BleedScore was the most inclusive. Over half of all patients experienced superficial event(s), most commonly occurring during two to three distinct bleeding episodes. There was no correlation between IPA and duration of antiplatelet therapy. Inhibition of platelet aggregation >50% strongly correlates with minor (r(2) = 0.58, P < 0.001; c-statistic = 0.92), but not severe (r(2) = 0.11, P = 0.038; c-statistic = 0.57), bleeding events. CONCLUSION: Chronic oral combination antiplatelet regimens are associated with a very high (56.5-60.7%) prevalence of superficial bleeding episodes, which are grossly underestimated in trials and registries. The role of such frequent mild complications for the overall benefit of antiplatelet therapy is entirely unknown, as is their effect on compliance. Although IPA is well suited for defining the risk of minor complications, prediction of more severe bleeding events may be challenging.

Evaluation of group concept mapping during advanced pharmacy practice experiences.

BACKGROUND AND PURPOSE: Concept mapping is an active learning tool associated with meaningful learning. In the pharmacy education literature, most evaluations of concept mapping focused solely on students' perceptions of mapping without evaluating its effectiveness on students' ability to apply the information learned. This article describes an evaluation of the effectiveness of group concept mapping during advanced pharmacy practice experiences (APPEs) by evaluating both application of the knowledge gained and students' reflections on the process. EDUCATIONAL ACTIVITY AND SETTING: Ambulatory care APPE students created group concept maps on pain management based on provided focus questions during a single session. Students completed pre-session and post-session tests comprised of the same multiple-choice questions that were derived from chapters on pain within licensure exam preparatory books. Additionally, students completed a survey after the group concept mapping session that assessed their thoughts on concept mapping. FINDINGS: Most students (92%) reported that concept mapping was an effective approach to learning, though there was not a statistically significant improvement in scores on the multiple-choice test. More than half (55%) of the students indicated the greatest gain in individual learning when actively discussing pain treatment related concepts amongst their group during concept map creation. Over 40% of students identified misconceptions related to pain management. SUMMARY: Using group concept mapping as a framework for discussions led to student integration of both concrete and abstract patient care concepts with individualized awareness of learning.

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.

Statin-related adverse events: a meta-analysis.

BACKGROUND: The absolute frequencies of adverse events (AEs) between statins and placebo are very low in clinical trials, making clinical interpretation and application difficult. OBJECTIVES: This meta-analysis was intended to synthesize the collective AE data observed in prospective randomized clinical trials to facilitate clinical interpretation. METHODS: Using the search terms atorvastatin, simvastatin,pravastatin, rosuvastatin, fluvastatin, lovastatin, prospective trial, and randomized trial, the MEDLINE/EMBASE and the Cochrane Collaboration databases were reviewed for prospective randomized primary and secondary prevention trials of statin monotherapy. Nonrandomized uncontrolled studies and those missing AE data were excluded. The Mantel-Haenszel test for fixed and random effects was used to calculate odds ratios (ORs) and log ORs. RESULTS: Eighteen trials including 71,108 persons, and 301,374 person-years of follow-up were represented in this analysis. There were 36,062 persons receiving a statin and 35,046 receiving a placebo. Statin therapy increased the risk of any AE by 39% (OR = 1.4; 95% CI, 1.09-1.80; P = 0.008; NNH [number needed to harm] = 197) compared with placebo. Statins were associated with a 26% reduction in the risk of a clinical cardiovascular event (OR = 0.74; 95% CI, 0.69-0.80; P < 0.001; number needed to treat = 27). Treating 1000 patients with a statin would prevent 37 cardiovascular events, and 5 AEs would be observed. Serious events (creatine phosphokinase >10 times the upper limit of normal or rhabdomyolysis) are infrequent (NNH = 3400) and rhabdomyolysis, although serious, is rare (NNH = 7428). Atorvastatin was associated with the greatest risk of AEs and fluvastatin with the least risk. Simvastatin, pravastatin, and lovastatin had similar odds of AEs. Nonurgent AEs such as myalgia and liver function elevations were responsible for approximately two thirds of AEs reported in trials. CONCLUSIONS: Statin therapy was associated with greater odds of AEs compared with placebo but with substantial clinical benefit. Similar rates of serious AEs were observed between statin and placebo.

Platelet inhibitors in non-ST-segment elevation acute coronary syndromes and percutaneous coronary intervention: glycoprotein IIb/IIIa inhibitors, clopidogrel, or both?

The role of glycoprotein (Gp) IIb/IIIa receptor antagonists remains controversial and these agents are infrequently utilized during non-ST-segment elevation acute coronary syndromes (NSTE-ACS) despite American Heart Association/American College of Cardiology guidelines. Despite recommendations, the NRMI-4 (National Registry of Myocardial Infarction 4) and CRUSADE (Can rapid risk stratification of unstable angina patients suppress adverse outcomes with early implementation of the ACC/AHA guidelines?) registries observed that only 25%-32% of eligible patients received early Gp IIb/IIIa therapy, despite a 6.3% absolute mortality reduction in NRMI-4 and a 2% absolute mortality reduction in CRUSADE. A pooled analysis of Gp IIb/IIIa data from these registries suggest a major reduction in mortality (Odds Ratio = 0.43, 95% Confidence Index 0.25-0.74, p = 0.002) with early Gp IIb/IIIa therapy, yet clinicians fail to utilize this option in NSTE-ACS. The evidence-based approach to NSTE-ACS involves aspirin, clopidogrel, low-molecular weight heparins, or unfractionated heparin in concert with Gp IIb/Ila receptor antagonists, however, newer percutaneous coronary intervention (PCI)-based trials challenge current recommendations. Novel strategies emerging in NSTE-ACS include omitting Gp IIb/Ila inhibitors altogether or using Gp IIb/IIIa inhibitors with higher doses of clopidogrel in selected patients. The ISAR-REACT (Intracoronary stenting and antithrombotic regimen-Rapid early action for coronary treatment) and ISAR-SWEET (ISAR-Is abciximab a superior way to eliminate elevated thrombotic risk in diabetics) trials question the value of abciximab when 600 mg of clopidogrel concurrently administered during PCI. The CLEAR-PLATELETS (Clopidogrel loading with eptifibatide to arrest the reactivity of platelets) and PEACE (Platelet activity extinction in non-Q-wave MI with ASA, clopidogrel, and eptifibatide) trials suggest more durable platelet inhibition when Gp IIb/IIIa inhibitors are used with higher doses clopidogrel. The ISAR-COOL (ISAR: Cooling off strategy) trial found no difference in ischemic outcomes when Gp IIb/IIIa inhibitors were excluded and ARMYDA-2 (Antiplatelet therapy for reduction of myocardial damage during angioplasty) suggested higher doses of clopidogrel are more appropriate during PCI when Gp IIb/IIIa inhibitors are not utilized. This constellation of new trials forces reconsideration of current recommendations in regards to patient risk stratification, choice of antithrombotic therapy, doses, and timing. These new data will impact emerging guidelines and updates are currently in progress.

Using personal digital assistants to document pharmacist cognitive services and estimate potential reimbursement.

The use of personal digital assistants (PDAs) to document pharmacist cognitive services and estimate potential reimbursement was studied. Between September 2001 and February 2002, four pharmacy residents and four clinical pharmacists used PDAs for documenting cognitive services. Interventions recorded on paper during the same six-month period one year earlier were reviewed for comparison. Potential reimbursement for these services was calculated by linking current procedural terminology codes and charges to the electronically documented services. Over the six-month study period, pharmacists recorded 7319 interventions with PDAs, compared with 5028 documented on paper during the earlier six-month period. Potential claims for pharmacists' cognitive services documented with PDAs amounted to more than $1 million in the six months, assuming a 100% reimbursement rate. PDAs provide a simple, efficient paperless system for documenting pharmacists' clinical services and generating reimbursement claims.

HMG-CoA reductase inhibitors for lowering elevated levels of C-reactive protein.

PURPOSE: Clinical trials evaluating the effectiveness of therapy with hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors for reducing elevated C-reactive protein (CRP) levels and associated coronary events are reviewed. SUMMARY: Atherosclerotic plaque growth may be attenuated with therapy aimed at minimizing inflammation. Because increased levels of CRP have been associated with arterial-wall inflammation, statins can prevent ischemia by both inhibiting deposition of lipids and decreasing inflammation. Evaluation of recent clinical trials, including WOSCOPS, PRINCE, AFCAPS/ TexCAPS, MIRACL, CURVES, REVERSAL, and JUPITER, demonstrated the correlation of statin therapy with decreased levels of CRP. WOSCOPS found that patients with CRP values of > 4.59 mg/L at baseline were at the highest risk of coronary events. The PRINCE trial evaluated the antiinflammatory effects of pravastatin and found a mean 16.9% reduction in CRP levels after 24 weeks of therapy. AFCAPS/TexCAPS researchers found that lovastatin provded a 14.8% reduction in the median levels of CRP (p < 0.001). The MIRACL study showed that atorvastatin reduced CRP levels by 83% (p < 0.001). Researchers in the CURVES study found a significant reduction in CRP levels with pravastatin, simvastatin, and atorvastatin compared with baseline (p < 0.025). Results of the REVERSAL study linked atorvastatin with a 36.4% decrease in CRP levels, while pravastatin was associated with a 5.2% decrease (p < 0.0001). JUPITER is ongoing and will determine whether long-term use of rosuvastatin can reduce the rate of coronary events. CONCLUSION: The lowering of elevated CRP levels by statins may reduce the risk of coronary events independently of the effect of statins on lipid levels.

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.

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.

Pharmacy student impact on inappropriate prescribing of acid suppressive therapy.

OBJECTIVE: To examine the impact that having pharmacy students on internal medicine patient care teams had on inappropriate prescribing of acid suppressive therapy (AST). METHODS: In this observational cohort study, internal medicine patients who received care from teams with a pharmacy student were compared to patients who received care from teams without a pharmacy student. The primary endpoint was proportion of patients on inappropriate AST. RESULTS: The overall proportion of patients receiving inappropriate AST was 24.4%. There was no significant difference between patients seen by teams with a pharmacy student and those seen by teams without a pharmacy student. The proportion of patients discharged with new inappropriate AST prescriptions was lower after pharmacy student review, though not significantly (6.1% vs. 9.4%, p = 0.07). Pharmacy student reviews shortened the median duration of inappropriate AST by 1.5 days (6 vs. 8.5 days, p = 0.025). CONCLUSIONS: Patient care teams on which pharmacy students performed medication reviews had a reduced duration of inappropriate use of AST in patients.

Post-PharmD industry fellowship opportunities and proposed guidelines for uniformity.

The focus of this paper is to examine the surge in the development of post-PharmD industry fellowships (ie, pharmacy fellowship programs sponsored by the biopharmaceutical or pharmaceutical industry). These post-PharmD training programs do not fit the currently accepted definition of a pharmacy fellowship; therefore, the authors propose a new and distinct definition to encompass these fellowships. The authors provide program examples to showcase the establishment of the post-PharmD industry fellowship institutional centers. Finally, the authors provide recommendations to create uniformity in the programs of this relatively new category of post-PharmD training.