Matthew A. Silva

Cost and Clinical Analysis of Autologous Hematopoietic Stem Cell Mobilization with G-CSF and Plerixafor Compared to G-CSF and Cyclophosphamide

Plerixafor plus granulocyte-colony stimulating factor (G-CSF) has been shown to mobilize more CD34(+) cells than G-CSF alone for autologous hematopoietic stem cell transplantation (HSCT). However, many centers use chemotherapy followed by G-CSF to mobilize CD34(+) cells prior to HSCT. We performed a retrospective study of patients who participated in the expanded access program (EAP) of plerixafor and G-CSF for initial mobilization of CD34(+) cells, and compared outcomes to matched historic controls mobilized with cyclophosphamide 3-5 g/m(2) and G-CSF at 2 centers that participated in the EAP Control patients were matched for age, sex, disease, disease stage, and number of prior therapies. Mobilization costs were defined to be the costs of medical procedures, resource utilization, and medications. Median national CMS reimbursement rates were used to establish the costs of procedures, hospitalization, provider visits, apheresis, CD34(+) cell processing and cryopreservation. Average sale price was used for G-CSF, plerixafor, cyclophosphamide, MESNA, antiemetics, and antimicrobials. A total of 33 patients from the EAP and 33 matched controls were studied. Two patients in the control group were hospitalized for neutropenic fever during the mobilization period. Apheresis started on the scheduled day in 33 (100%) study patients and in 29 (88%) control patients (P = 0.04). Sixteen (48%) control patients required weekend apheresis. There was no difference in number of CD34(+) cells collected between the groups, and all patients proceeded to HSCT with no difference in engraftment outcomes. Median total cost of mobilization was not different between the plerixafor/G-CSF and control groups (

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

14,224 versus

Plerixafor: A chemokine receptor-4 antagonist for mobilization of hematopoietic stem cells for transplantation after high-dose chemotherapy for non-hodgkin's lymphoma or multiple myeloma

18,824; P = .45). In conclusion, plerixafor/G-CSF and cyclophosphamide/G-CSF for upfront mobilization of CD34(-) cells resulted in similar numbers of cells collected, costs of mobilization, and clinical outcomes. Additionally, plerixafor/G-CSF mobilization resulted in more predictable days of collection, no weekend apheresis procedures, and no unscheduled hospital admissions.

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

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 Antiplatelet Agents for Secondary Prevention of Stroke Using Mixed Treatment Comparison Meta-analysis

BACKGROUND Autologous hematopoietic stem cell (HSC) transplantation is used to facilitate hematopoietic recovery after administration of high-dose chemotherapy in patients with Hodgkins disease, non-Hodgkins lymphoma (NHL), multiple myeloma (MM), leukemias, and some solid tumors. There are limitations to the existing methods of mobilizing CD34+ HSC with chemotherapy and/or granulocyte colony-stimulating factor (G-CSF). Plerixafor, a bicyclam molecule that acts as a pure antagonist of chemokine receptor-4, is approved by the US Food and Drug Administration for use in combination with G-CSF for mobilization of CD34+ HSC in patients with NHL or MM. OBJECTIVE This review presents information on plerixafor, including its mechanism of action in mobilizing stem cells, pharmacokinetics, clinical efficacy, adverse effects, and pharmacoeconomic considerations. METHODS MEDLINE, EMBASE (1996-June 2009), and International Pharmaceutical Abstracts (1970-June 2009) were searched on July 9, 2009, using the key words plerixafor and AMD3100 for reports relating to HSC mobilization. The search was updated on September 20, 2009, and again on January 30, 2010. The reference lists of identified articles were examined for additional abstracts and other sources of information. The journal Blood was searched online to identify abstracts presented at Annual Meetings of the American Society of Hematology. RESULTS After administration of plerixafor, HSC migrate from the bone marrow into the peripheral blood, permitting collection by apheresis. Clinical trials in humans have found that the combination of G-CSF + plerixafor facilitates mobilization of HSC. In patients with MM without extensive previous treatment who were undergoing a first mobilization, the use of G-CSF + plerixafor was reported to double counts of circulating peripheral CD34+ HSC and thus double the number of CD34+ HSC collected in half as many apheresis procedures, although rates of engraftment, graft durability, transplantation, and survival outcomes were not significantly improved. In patients with Hodgkins disease or NHL, in whom limited success in mobilization is expected, G-CSF + plerixafor also facilitated or improved mobilization with improved apheresis yields, again without significant improvement in outcomes. Common (> or = 20%) adverse events of plerixafor used in combination with G-CSF include diarrhea (37%), nausea (34%), injection-site reactions (34%), fatigue (27%), and headache (22%). Plerixafor 0.24 mg/kg SC is administered on the evening of the fourth day of G-CSF dosing, approximately 11 hours before the first apheresis session. Daily doses of plerixafor can be repeated up to 3 times on consecutive days to achieve adequate HSC collection. The average wholesale price of a 24-mg vial of plerixafor is

Meta-analysis of Ivabradine in Patients With Stable Coronary Artery Disease With and Without Left Ventricular Dysfunction

7500. CONCLUSIONS Plerixafor is an effective agent for mobilizing CD34+ HSC. Long-term treatment outcomes are being studied in patients undergoing autologous transplantation of HSC mobilized with G-CSF + plerixafor.

Improving Population Health Through Integration of Primary Care and Public Health: Providing Access to Physical Activity for Community Health Center Patients

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.

Evaluation of Oral Anticoagulants for the Extended Treatment of Venous Thromboembolism Using a Mixed-Treatment Comparison, Meta-Analytic Approach

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.

Creating open access to exercise for low-income patients through a community collaboration for quality improvement: if you build it, they will come.

PURPOSE Ivabradine is a novel If-channel antagonist that controls heart rate and may be helpful in treating patients with left ventricular dysfunction (LVD) who are unable to tolerate β-blockers or achieve a heart rate of 70 beats/min with standard therapy. Three landmark trials were used for the approval of ivabradine in the United States. These trials tested ivabradine in addition to a standard of care (including β-blockers) in patients with stable coronary artery disease (CAD) and found modest benefit in those with established LVD unable to tolerate β-blockers. The goal of this review was to pool data from ivabradine studies in all patients with stable CAD to compare cardiovascular and safety-related outcomes. METHODS Three randomized, double-blind, placebo-controlled trials of ivabradine added to standard treatment (including β-blockers) in patients with stable CAD with and without LVD were reviewed for effects on mortality, cardiovascular outcomes, and adverse events. Data were independently abstracted by 2 reviewers; the Oxford quality scoring system was used to evaluate randomization, blinding, withdrawals, and dropouts; and a Mantel-Haenszel random effects pairwise meta-analysis was used to combine data into odds ratios. FINDINGS The initial search identified 116 trials; 3 of these trials, representing 36,524 patients with stable CAD, met inclusion criteria. According to the pooled results, ivabradine did not consistently reduce all-cause mortality (odds ratio [OR], 1.00 [95% CI, 0.91-1.11]; P = 0.98], cardiovascular death (OR, 1.02 [95% CI, 0.91-1.15]; P = 0.74), or hospitalization for worsening or new onset heart-failure in patients with stable CAD (OR, 0.94 [95% CI, 0.71-1.25]; P = 0.69). Ivabradine did not increase serious adverse drug reactions (OR, 0.99 [95% CI, 0.88-1.13]; P = 0.93) or cardiac disorders (OR, 1.03 [95% CI, 0.87-1.22]; P = 0.74). However, it was associated with drug-specific effects, including new-onset atrial fibrillation (OR, 1.35 [95% CI, 1.19-1.53]; P < 0.001], bradycardia (OR, 6.54 [95% CI, 3.30-12.9]; P < 0.001), phosphenes (OR, 7.77 [95% CI, 4.12-14.63]; P < 0.001), and blurry vision (OR, 3.07 [95% CI, 2.18-4.32]; P < 0.001). IMPLICATIONS Unselective use of ivabradine in patients with stable CAD is not supported by evidence and can be associated with new-onset atrial fibrillation, bradycardia, and drug-related nuisance adverse events.

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

OBJECTIVES Our community health center attempted to meet public health goals for encouraging exercise in adult patients vulnerable to obesity, diabetes, hypertension, and other chronic diseases by partnering with a local YMCA. METHODS During routine office visits, providers referred individual patients to the YMCA at no cost to the patient. After 2 years, the YMCA instituted a