Effect of outpatient pharmacists' non-dispensing roles on patient outcomes and prescribing patterns.

BACKGROUND: The roles of pharmacists in patient care have expanded from the traditional tasks of dispensing medications and providing basic medication counseling to working with other health professionals and the public. Multiple reviews have evaluated the impact of pharmacist-provided patient care on health-related outcomes. Prior reviews have primarily focused on in-patient settings. This systematic review focuses on services provided by outpatient pharmacists in community or ambulatory care settings. This is an update of the Cochrane review published in 2000. OBJECTIVES: To examine the effect of outpatient pharmacists' non-dispensing roles on patient and health professional outcomes. SEARCH STRATEGY: This review has been split into two phases. For Phase I, we searched the Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register (January 1966 through March 2007). For Phase II, we searched MEDLINE/EMBASE (January 1966 through March 2008). The Phase I results are reported in this review; Phase II will be summarized in the next update. SELECTION CRITERIA: Randomized controlled trials comparing 1. Pharmacist services targeted at patients versus services delivered by other health professionals; 2. Pharmacist services targeted at patients versus the delivery of no comparable service; 3. Pharmacist services targeted at health professionals versus services delivered by other health professionals; 4. Pharmacist services targeted at health professionals versus the delivery of no comparable service. DATA COLLECTION AND ANALYSIS: Two authors independently reviewed studies for inclusion, extracted data, and assessed risk of bias of included studies. MAIN RESULTS: Forty-three studies were included; 36 studies were pharmacist interventions targeting patients and seven studies were pharmacist interventions targeting health professionals. For comparison 1, the only included study showed a significant improvement in systolic blood pressure for patients receiving medication management from a pharmacist compared to usual care from a physician. For comparison 2, in the five studies evaluating process of care outcomes, pharmacist services reduced the incidence of therapeutic duplication and decreased the total number of medications prescribed. Twenty-nine of 36 studies reported clinical and humanistic outcomes. Pharmacist interventions resulted in improvement in most clinical outcomes, although these improvements were not always statistically significant. Eight studies reported patient quality of life outcomes; three studies showed improvement in at least three subdomains. For comparison 3, no studies were identified meeting the inclusion criteria. For comparison 4, two of seven studies demonstrated a clear statistically significant improvement in prescribing patterns. AUTHORS' CONCLUSIONS: Only one included study compared pharmacist services with other health professional services, hence we are unable to draw conclusions regarding comparisons 1 and 3. Most included studies supported the role of pharmacists in medication/therapeutic management, patient counseling, and providing health professional education with the goal of improving patient process of care and clinical outcomes, and of educational outreach visits on physician prescribing patterns. There was great heterogeneity in the types of outcomes measured across all studies. Therefore a standardized approach to measure and report clinical, humanistic, and process outcomes for future randomized controlled studies evaluating the impact of outpatient pharmacists is needed. Heterogeneity in study comparison groups, outcomes, and measures makes it challenging to make generalised statements regarding the impact of pharmacists in specific settings, disease states, and patient populations.

Discrimination of common and unique RNA-binding activities among Fragile X mental retardation protein paralogs.

Fragile X mental retardation is caused by loss-of-function of a single gene encoding FMRP, an RNA-binding protein that harbors three canonical RNA-binding domains, two KH-type and one RGG box. Two autosomal paralogs of FMRP, FXR1P and FXR2P, are similar to FMRP in their overall structure, including the presence of putative RNA-binding domains, but to what extent they provide functional redundancy with FMRP is unclear. Although FMRP has been characterized as a polyribosome-associated regulator of translation, less is known about the functions of FXR1P and FXR2P. For example, FMRP binds intramolecular G-quadruplex and kissing complex RNA (kcRNA) ligands via the RGG box and KH2 domain, respectively, although the RNA ligands of FXR1P and FXR2P are unknown. Here we demonstrate that FXR1P and FXR2P KH2 domains bind kcRNA ligands with the same affinity as the FMRP KH2 domain although other KH domains do not. RNA ligand recognition by this family is highly conserved, as the KH2 domain of the single Drosophila ortholog, dFMRP, also binds kcRNA. kcRNA was able to displace FXR1P and FXR2P from polyribosomes as it does for FMRP, and this displacement was FMRP-independent. This suggests that all three family members recognize the same binding site on RNA mediating their polyribosome association, and that they may be functionally redundant with regard to this aspect of translational control. In contrast, FMRP is unique in its ability to recognize G-quadruplexes, suggesting the FMRP RGG domain may play a non-redundant role in the pathophysiology of the disease.

Kissing complex RNAs mediate interaction between the Fragile-X mental retardation protein KH2 domain and brain polyribosomes.

Fragile-X mental retardation is caused by loss of function of a single gene encoding the Fragile-X mental retardation protein, FMRP, an RNA-binding protein that harbors two KH-type and one RGG-type RNA-binding domains. Previous studies identified intramolecular G-quartet RNAs as high-affinity targets for the RGG box, but the relationship of RNA binding to FMRP function and mental retardation remains unclear. One severely affected patient harbors a missense mutation (I304N) within the second KH domain (KH2), and some evidence suggests this domain may be involved in the proposed role of FMRP in translational regulation. We now identify the RNA target for the KH2 domain as a sequence-specific element within a complex tertiary structure termed the FMRP kissing complex. We demonstrate that the association of FMRP with brain polyribosomes is abrogated by competition with the FMRP kissing complex RNA, but not by high-affinity G-quartet RNAs. We conclude that mental retardation associated with the I304N mutation, and likely the Fragile-X syndrome more generally, may relate to a crucial role for RNAs harboring the kissing complex motif as targets for FMRP translational regulation.