Patient satisfaction with warfarin- and non-warfarin-containing thromboprophylaxis regimens for atrial fibrillation.

OBJECTIVE: To compare patient-reported limitations, concerns, and burdens in those receiving and not receiving warfarin for thromboprophylaxis in atrial fibrillation (AF). METHODS: We conducted a cross-sectional survey study of patients with AF receiving thromboprophylaxis for stroke prevention. Patients were administered the validated Anti-Clot Treatment Scale (ACTS). Mean scores of patients receiving and not receiving warfarin were compared for each ACTS item, and for the Burden and Benefit subscales. RESULTS: From July 2010 to August 2011, 80 patients with AF were administered the survey, with 65 patients receiving a regimen containing warfarin and 15 patients not receiving a regimen containing warfarin. Six of the 17 individual questions depicting patient- perceived limitations in physical activity due to bleeding, limitations on diet, feelings of inconvenience of occasional aspects of thromboprophylaxis therapy, and frustration, and burden had less favorable scores in the warfarin-managed patients compared with the patients not receiving warfarin (P < 0.05 for all). Mean ACTS Burden scores were more favorable in the no-warfarin group (44.5 ± 6.4) compared with the warfarin group (39.8 ± 8.0; P = 0.003). No difference was seen between the 2 groups on the ACTS Benefits score (11.1 ± 3.4 vs 10.4 ± 3.7; P = 0.38). CONCLUSION: Patients with AF receiving warfarin may have less favorable feelings regarding thromboprophylaxis versus those receiving non-warfarin thromboprophylaxis. Patients report having more limitations and having greater feelings of burden on warfarin.

Efficacy and safety of innovator versus generic drugs in patients with epilepsy: a systematic review.

Generic antiepileptic drugs achieve blood concentrations similar to those of innovator drugs in healthy volunteers, but their comparative effectiveness has not been well evaluated. Thus, we assessed the efficacy, tolerability, and safety of innovator versus generic antiepileptic drugs. We searched the MEDLINE database, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Web of Science for studies that evaluated innovator and generic antiepileptic drugs in patients with epilepsy and reported data on prespecified outcomes. We extracted data on study design, interventions, quality criteria, study population, baseline characteristics, and outcomes. Compared with initiation of innovator antiepileptic drugs, initiation of generic antiepileptic drugs did not significantly alter seizure occurrence (relative risk [RR] 0.87, 95% confidence interval [CI] 0.64-1.18; strength of evidence: low) or frequency (standardized mean difference 0.03, 95% CI -0.08-0.14; strength of evidence: low), withdrawals due to lack of efficacy (RR 1.02, 95% CI 0.41-2.54; strength of evidence: low) or adverse events (RR 0.79, 95% CI 0.28-2.20; strength of evidence: low), pharmacokinetic concentrations (maximum, minimum, or area under the curve [strength of evidence: low]), or a myriad of adverse events (strength of evidence: low or insufficient) in clinical trials. In qualitatively evaluated observational studies, switching between forms of antiepileptic drug (innovator to generic, generic to generic) may increase the risk of hospitalization (strength of evidence: low), hospital stay duration (strength of evidence: low), and a composite end point of medical service utilization (strength of evidence: insufficient) but may not increase outpatient service utilization (strength of evidence: low). Data are limited predominantly to carbamazepine, phenytoin, and valproic acid. Clinical trials are limited by small sample size, short-term nature, and lack of specification of A-rated generic products (generics that the United States Food and Drug Administration has deemed bioequivalent to the innovator drug). Observational trials lack full accounting for confounders and have inherent limitations. With a low strength of evidence, it appears that initiating an innovator or generic antiepileptic drug will provide similar efficacy, tolerability, and safety but that switching from one form to the other may be associated with more hospitalizations and longer hospital stays.

Effect of pharmacist intervention on glycemic control in diabetes.

AIM: To conduct a meta-analysis evaluating the effect of pharmacist intervention on glycemic control. METHODS: A systematic search of Medline and CENTRAL was conducted from the earliest possible date through June 2010. Trials were included if they were randomized controlled trials in a diabetic population, evaluated any form of pharmacist intervention and reported data on hemoglobin A1C (A1C). A random-effects model was used to calculate weighted mean differences (WMDs) and 95% confidence intervals. RESULTS: Fourteen trials (n = 2073) evaluating the effect of pharmacist intervention on glycemic control were identified. Pharmacist intervention significantly lowered A1C (n = 14 trials, WMD -0.76%, 95%CI -1.06 to -0.47) and fasting blood glucose (FBG) (n = 4 trials, WMD -29.32 mg/dL, 95%CI -39.54 to -19.10). A moderate to high degree of statistical heterogeneity was observed in these analyses (I(2) ≥ 44.1% for both). CONCLUSIONS: Our findings demonstrate statistically and clinically significant associations between pharmacist intervention and improvement in glycemic control.

Recombinant human growth hormone in the treatment of patients with cystic fibrosis.

CONTEXT: Recombinant human growth hormone (rhGH) improves growth in patients with growth hormone deficiency or idiopathic short stature. Its role in patients with cystic fibrosis (CF) is unclear. OBJECTIVE: To review the effectiveness of rhGH in the treatment of patients with CF. METHODS: Medline and the Cochrane Central Register of Controlled Trials were searched from the earliest date through April 2010. Randomized controlled trials, observational studies, systematic reviews/meta-analyses, or case reports were included if rhGH therapy was administered to patients with CF and data on prespecified harms, intermediate outcomes, or final health outcomes were reported. When applicable, end points were pooled by using a random-effects model. The overall body of evidence was graded for each outcome as insufficient, low, moderate, or high. RESULTS: Ten unique controlled trials (n = 312) and 8 observational studies (n = 58) were included. On quantitative synthesis of controlled trials, several markers of pulmonary function, anthropometrics, and bone mineralization were significantly improved versus control. Results of single-arm observational studies for the aforementioned outcomes were generally supportive of findings in clinical trials. There is insufficient evidence to determine the effect of rhGH on intravenous antibiotic use during therapy, pulmonary exacerbations, health-related quality-of-life, bone consequences, or total mortality, but moderate evidence suggests that rhGH therapy reduces the rate of hospitalization versus control. CONCLUSIONS: rhGH improved almost all intermediate measures of pulmonary function, height, and weight in patients with CF. Improvements in bone mineral content are also promising. However, with the exception of hospitalizations, the benefits on final health outcomes cannot be directly determined at this time.

Effect of noninsulin antidiabetic drugs added to metformin therapy on glycemic control, weight gain, and hypoglycemia in type 2 diabetes.

CONTEXT: Metformin is the recommended initial drug therapy for patients with type 2 diabetes mellitus (DM). However, the optimal second-line drug when metformin monotherapy fails is unclear. OBJECTIVE: To determine the comparative efficacy, risk of weight gain, and hypoglycemia associated with noninsulin antidiabetic drugs in patients with type 2 DM not controlled by metformin alone. DATA SOURCES: A literature search via MEDLINE (beginning in January 1950) and Cochrane CENTRAL through January 2010 and a manual search of references for additional relevant studies. STUDY SELECTION: Randomized controlled trials (RCTs) with at least 3 months' duration, evaluating noninsulin antidiabetic drugs added to metformin in patients experiencing an inadequate response to maximized and stable (> or = 4 weeks at > or = 1500 mg or maximally tolerated dose) metformin therapy. DATA EXTRACTION: Inclusion/exclusion criteria; duration of patient follow-up; drug, dose, and schedule used; use of concurrent lifestyle modification; and baseline characteristics (age, sex, anthropometrics, glycated hemoglobin A(1c) [HbA(1c)], duration of DM, and metformin dose). End points collected included mean change in HbA(1c), proportion of patients achieving HbA(1c) goal of less than 7%, change in weight, and incidence of hypoglycemia. Mixed-treatment comparison meta-analysis was used to calculate the weighted mean difference for changes from baseline in HbA(1c) and body weight and relative risk (RR) of HbA(1c) goal attainment and hypoglycemia, with associated 95% credible intervals. DATA SYNTHESIS: Overall, 27 RCTs (n = 11 198) were included. Mean (range) trial duration was 32 (12-52) weeks. The different classes of drugs were associated with similar HbA(1c) reductions (range, 0.64%-0.97%) compared with placebo. Although use of thiazolidinediones, sulfonylureas, and glinides were associated with weight gain (range, 1.77-2.08 kg), glucagon-like peptide-1 analogs, alpha-glucosidase inhibitors, and dipeptidyl peptidase-4 inhibitors were associated with weight loss or no weight change. Sulfonylureas and glinides were associated with higher rates of hypoglycemia than with placebo (RR range, 4.57-7.50). CONCLUSION: When added to maximal metformin therapy, all noninsulin antidiabetic drugs were associated with similar HbA(1c) reductions but differed in their associations with weight gain and risk of hypoglycemia.

The effect of adding plant sterols or stanols to statin therapy in hypercholesterolemic patients: systematic review and meta-analysis.

OBJECTIVE: To characterize the effect of plant sterols/stanols on serum lipids in hypercholesterolemic patients on concurrent statin therapy, we conducted a meta-analysis of randomized controlled trials. METHODS: A systematic literature search of MEDLINE, EMBASE, Cochrane CENTRAL, and the Natural Medicines Comprehensive Database was conducted from the earliest possible date through May 2008. Trials were included in the analysis if they were randomized controlled trials evaluating the use of plant sterols/stanols in combination with statins in hypercholesterolemic patients that reported efficacy data on total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, or triglycerides. The weighted mean difference (WMD) of the change from baseline (in mg/dL) with 95% confidence interval (CI) was calculated as the difference between the mean in the plant sterol/stanol groups and the control groups, using a random-effects model. RESULTS: Eight studies (n = 306 patients) met the inclusion criteria. Upon meta-analysis, the use of plant sterols/stanols in combination with statin therapy significantly lowered total cholesterol (WMD, -14.01 mg/dL [95% CI, -18.66 to -9.37], p < 0.0001) and LDL cholesterol (WMD, -13.26 mg/dL [95% CI, -17.34 to -9.18], p < 0.0001) but not HDL cholesterol or triglycerides. CONCLUSIONS: Based upon the current literature, we can only say that plant sterols/stanols, when administered in addition to statins, favorably affect total and LDL cholesterol with 95% confidence. Randomized trials examining the impact of plant sterols/stanols in combinatation with statins on patient morbidity and mortality are needed.