Sensitivity of patient outcomes to pharmacist interventions. Part III: systematic review and meta-analysis in hyperlipidemia management.

BACKGROUND: Hyperlipidemia increases the risk of cardiovascular diseases, and control is pivotal for preventing disease complications. Multidisciplinary interventions, including those performed by pharmacists, are important for improving patients' outcomes. OBJECTIVE: To quantify the impact of pharmacist interventions in enhancing patients' outcomes. METHODS: Two reviewers searched International Pharmaceutical Abstracts, MEDLINE, EMBASE, The Cochrane Central Register of Controlled Trials, 3rd Quarter, and Cumulative Index to Nursing and Allied Health Literature (all from inception to July 2007) for pharmacist interventions in hyperlipidemia. Quality was assessed using the Downs-Black scale. Data extracted included the number of patients enrolled; study characteristics; intervention type; and pre- and postintervention measures for low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, total cholesterol, adherence, and quality of life. A random effects meta-analysis combined data. Heterogeneity of effects was tested using chi(2) analysis. Publication bias was assessed using funnel plots and the Begg-Mazumdar statistic. RESULTS: Forty-eight studies were found; 23 met inclusion criteria. Study settings included medical clinic/center (n = 12), community pharmacy (n = 8), hospital (n = 2), and patient homes (n = 1). Article quality was good (71% +/- 7.0%). Patient education (78%) and medication management (74%) were the most common interventions. Total cholesterol was significantly reduced from baseline (mean +/- SD; 34.3 +/- 10.3 mg/dL; p < 0.001) and above that for controls (22.0 +/- 10.4 mg/dL; p = 0.034). LDL-C was reduced significantly from baseline (32.6 +/- 11.3 mg/dL; p = 0.004), but not significantly more than controls (17.5 +/- 10.9 mg/dL; p = 0.109). A clinically relevant but not statistically significant reduction in triglycerides was found. No impact on HDL-C levels was found. Patients' adherence to pharmacotherapeutic regimens and quality of life were considered possibly not sensitive and possibly sensitive to pharmacist interventions, respectively. CONCLUSIONS: Total cholesterol is sensitive to pharmacist interventions, while LDL-C and triglyceride levels are possibly sensitive to those interventions. Further research is required for these outcomes.

Sensitivity of patient outcomes to pharmacist interventions. Part II: Systematic review and meta-analysis in hypertension management.

BACKGROUND: Hypertension is a major health concern worldwide due to its deleterious impact. Few studies have quantitatively assessed pharmacists' interventions in hypertensive patients. OBJECTIVES: To identify and quantify outcomes sensitive to pharmacists' interventions. METHODS: International Pharmaceutical Abstracts, MEDLINE, Cochrane Central, and EMBASE were searched from inception through December 2006. Two independent reviewers identified articles; results were compared and resolved through consensus. Data extracted included intervention type, patient numbers, demographics, study characteristics, instruments used, data compared, and outcomes reported. A random effects meta-analysis was used to combine data. Study quality was assessed using the Downs-Black scale. RESULTS: Of 203 potential articles identified, 98 were selected and their abstracts were read. Nine of these were reviewed full-text and 19 more were identified from references, resulting in a total of 28 articles. Research designs included 18 randomized controlled trials, 6 single-arm clinical trials, 3 nonrandomized comparative trials, and 1 database study. Average quality score was 66% +/- 12% (fair). Medication management (82%) and hypertension education (68%) were the interventions most used. Thirty-nine study results (57% of all outcomes evaluated) were sensitive to pharmacists' interventions. Meta-analysis of 2246 patients in 13 studies found that pharmacists' interventions significantly reduced systolic blood pressure (10.7 +/- 11.6 mm Hg; p = 0.002), while controls remained unchanged (3.2 +/- 12.1 mm Hg; p = 0.361). Pharmacists' interventions further reduced systolic blood pressure (6.9 +/- 12.1 mm Hg; p = 0.047) over controls. Nonsensitive results included further reduction in diastolic blood pressure (3.6 +/- 3.7 mm Hg; p = 0.06), quality of life (1 of 8 significant), and adherence (5 of 13 significant). CONCLUSIONS: Systolic blood pressure is sensitive to pharmacists' interventions. Other outcomes may also be sensitive; however, more high-quality studies are needed for a comprehensive quantitative assessment.

Sensitivity of patient outcomes to pharmacist interventions. Part I: systematic review and meta-analysis in diabetes management.

BACKGROUND: Pharmacists participate in managing diabetes therapy. Despite many reviews, few have quantified the impact of pharmacists' interventions. OBJECTIVES: To identify outcomes sensitive to pharmacists' interventions and quantify their impact through critical literature review. METHODS: All original research describing the impact of pharmacists' interventions in the management of diabetic pharmacotherapy was sought in International Pharmaceutical Abstracts, MEDLINE, Embase, Cochrane Register, and Cumulative Index to Nursing & Allied Health Literature from inception through 2006. Two independent reviewers identified articles, compared results, and settled differences through consensus. The Downs-Black scale was used to assess quality. Data included intervention type, patient numbers, demographics, study characteristics, instruments used, data compared, and outcomes reported. A random-effects meta-analysis combined amenable results. RESULTS: Of 302 articles identified, 108 involved pharmacists' interventions; 36 addressed diabetes (14 medical clinics, 11 community pharmacies, 7 ambulatory care clinics, 4 hospital wards, 1 physician's office, 1 prison, and 3 in both medical clinics and community pharmacies; 1 did not describe its practice site). Research designs included randomized (n = 18) and nonrandomized (n = 9) controlled trials, pre- and postobservational cohorts (n = 2), retrospective cohort study (n = 1), chart reviews (n = 5), and database study (n = 1). Diabetes education (69%) and medication management (61%) were the most frequently used interventions. Mean +/- SD quality was 62 +/- 11% (fair). Fifty-one (69%) study results were sensitive. Meta-analysis of data from 2247 patients in 16 studies found a significant reduction in hemoglobin A1C (A1C) levels in the pharmacists' intervention group (1.00 +/- 0.28%; p < 0.001) but not in controls (0.28 +/- 0.29%; p = 0.335). Pharmacists' interventions further reduced A1C values 0.62 +/- 0.29% (p = 0.03) over controls. CONCLUSIONS: A1C is sensitive to pharmacists' interventions. Several potentially sensitive outcomes were identified, but too few studies were available for quantitative summaries. More research is needed.

Pharmacokinetics of dihydroergocristine and its major metabolite 8'-hydroxy-dihydroergocristine in human plasma.

Dihydroergocristine (DHEC) is a semi-synthetic drug mainly used for age-related cognitive impairment. In this study, its major metabolite 8'-hydroxy-dihydroergocristine (8'-OH-DHEC) was produced in incubates of a bovine liver preparation using dihydroergocristine mesylate (DHECM) as substrate. Purification was achieved by flash silica gel column and reverse phase liquid chromatographies, and identification was based on accurate molecular mass measurements, mass fragmentation spectra and NMR ((1)H/(13)C) chemical shifts. By using the substance produced in vitro, a fast, sensitive, specific and robust LC/MS/MS method for the simultaneous determination of DHEC and its major metabolite in human plasma was developed and validated. Bromocriptine was used as internal standard and limits of quantification for DHEC and 8'-OH-DHEC were 10 pg/ml and 20 pg/ml, respectively. Pharmacokinetic parameters were investigated on 12 male healthy volunteers to whom a single dose of 18 mg DHECM was administered in tablets (Iskevert). The peak of DHEC was 0.28 +/- 0.22 microg/l, the t(max) 0.46 +/- 0.26 h, the AUC(last) 0.39 +/- 0.41 microg/l.h and the terminal elimination half-life 3.50 +/- 2.27 h. The peak of 8'-OH-DHEC was 5.63 +/- 3.34 microg/l, the t(max) 1.04 +/- 0.66 h, the AUC(last) 13.36 +/- 5.82 microg/l.h and the terminal elimination half-life 3.90 +/- 1.07 h. Dosing of 18 mg DHECM was well tolerated, causing no adverse events.