Dose response with onabotulinumtoxinA for post-stroke spasticity: a pooled data analysis.

Clinical trials demonstrate that onabotulinumtoxinA reduces upper limb post-stroke spasticity, with therapeutic response influenced by injected dose. Individual studies provide limited insight regarding muscle group-specific dose-response relationships. Our objective was to characterize dose-response relationships between onabotulinumtoxinA and muscle tone in specific upper limb muscles. Individual patient data from seven multicenter, randomized, double-blind, placebo-controlled trials were pooled. Of 544 post-stroke patients enrolled, 362 received onabotulinumtoxinA and 182 received placebo, injected into the flexor carpi radialis (FCR), flexor carpi ulnaris (FCU), flexor digitorum superficialis (FDS), flexor digitorum profundus (FDP), and/or biceps brachii (BB). Ashworth Scale score change at week 6 (AshworthCBL) was the primary outcome measure for muscle tone. For a broader analysis of response, AshworthCBL/onabotulinumtoxinA dosage relationships were characterized using three techniques: (1) AshworthCBL plotted as a function of onabotulinumtoxinA dose in Units (U) [dose-response curve]; (2) mean AshworthCBL per onabotulinumtoxinA dose depicting the responses seen with specific dose injection clusters/groups for each specific muscle group; and (3) onabotulinumtoxinA dose estimated to produce a mean 1-point decrease in AshworthCBL as an indicator of clinically meaningful benefit of treatment. Increasing onabotulinumtoxinA doses produced greater AshworthCBLs (muscle tone improvements). The maximal week 6 response (E(max)) model indicated a saturating dose-response relationship, with mean E(max) AshworthCBL values of -1.48, -1.48, -0.63, -0.77, and -0.61 in the FCR, FCU, FDS, FDP, and BB, respectively. OnabotulinumtoxinA doses estimated to produce a mean 1-point decrease in AshworthCBL were: 22.5U, 18.4U, 66.3U, 42.5U in the FCR, FCU, FDS, and FDP, respectively, and not determinable in the BB. These analyses demonstrate a saturating effect of greater muscle tone improvements with increasing onabotulinumtoxinA doses in post-stroke spasticity patients. These findings suggest potentially effective onabotulinumtoxinA doses in selected muscle groups in this study population.

Cost-justification of a clinical pharmacist-managed anticoagulation clinic.

A cost-benefit evaluation of a clinical pharmacist-managed anticoagulation clinic (AC) was performed. Outpatient and hospital records were examined for 26 patients in the treatment group with an AC clinic and 26 patients in the control group. Therapeutic prothrombin times were maintained within the treatment group to a significantly greater extent than within the control group (p<0.001). The AC was successful in preventing hospitalizations resulting from hemorrhage or thromboembolic admissions (p<0.05, p<0.005, respectively). Patients were hospitalized 3.22 days and .048 days per patient-treatment-year in the control and treatment groups, respectively. The net savings in reduced hospitalization costs per year in the treatment group was $211,776. The benefit:cost ratio (B:C) was 6.55, suggesting the program is socially valuable. This clinical pharmacist-managed AC was effective in maintaining therapeutic prothrombin times, and reducing the incidence of hospitalizations resulting from anticoagulation complications, and can be cost-justified based on a cost-benefit analysis.

Widespread use of fluoroquinolones versus emerging resistance in pneumococci.

During the past decade, respiratory-tract pathogens have shown an increase in resistance to all classes of antimicrobial agents. Although the increasing prevalence of penicillin-resistant Streptococcus pneumoniae has resulted in an increased reliance on newer classes of agents, such as the fluoroquinolones, the broad use of these agents has contributed to increasing prevalence of strains with in vitro fluoroquinolone resistance, which are associated with treatment failures, nosocomial outbreaks, and patient fatalities. Strategies to limit this emerging dilemma and preserve the clinical utility of these agents are needed.