Patient baseline characteristics are summarized in

Table 1. Six women were receiving ART prior to pregnancy. The median (range) time on treatment until the first antepartum pharmacokinetic sampling in these subjects was 125 (23–236) weeks. Five patients were receiving LPV/r-based therapy, whereas one patient initially received nelfinavir but switched to LPV/r at 30 weeks’ gestation as a result of the withdrawal of nelfinavir from the market at this selleck time. Five of the six women had an undetectable pVL at baseline. Forty women (17 treatment-naïve, 16 treatment-experienced and seven of unknown treatment status) initiated LPV/r therapy in pregnancy. All took LPV for at least 2 weeks prior to the first TDM. The median (range) gestational age at the time of treatment initiation in these patients was 25 (15–36) weeks. Forty-four

patients (96%) at baseline were prescribed the LPV/r tablet at the standard dose of 400/100 mg twice daily. However, one patient received four tablets (800/200 mg) once daily and another initially received LPV/r, underwent TDM in the second trimester, but was later (at 28 weeks’ gestation) switched to boosted atazanavir because of nausea. The NRTI backbone was primarily zidovudine+lamivudine (Combivir, GlaxoSmithKline, London, UK) in 41 (89%) patients. LPV (total and unbound) and RTV (total) trough concentrations were determined in three patients in the first trimester, 13 in the second [for the purpose of subsequent statistical analysis pharmacokinetic data from the first and second selleck inhibitor trimesters were combined (n=16), as presented

in Table 2] and 43 patients in the third trimester. Median (range) gestational age at the time of pharmacokinetic sampling was 8 (8–11) weeks in the first trimester, 24 (17–29) weeks in the second trimester and 31 (26–40) weeks in the third trimester. In addition, 12 patients had measurements taken postpartum. Median (range) follow-up time after delivery was 8 (5–12) weeks. At the time nearest to delivery, 32 patients (70%) had undetectable pVL, eight patients clonidine (17%) had detectable pVL [median (range) 80 (56–418) copies/mL] and six patients (13%) were unavailable (two were lost to follow-up, two were transferred to another maternity unit, one had a miscarriage, and one result was not applicable). Eight subjects had pVL measurements taken in conjunction with pharmacokinetic sampling postpartum; all were undetectable. Thirty-one patients (67%) achieved pVL <50 copies/mL at a median (range) of 11 (2–33) weeks. Six patients (13%) had undetectable pVL pre-pregnancy, five of whom were on ART prior to conception. Fourteen patients (30%) remained on ART postpartum for their own health. There were 42 live births (one set of twins) and one miscarriage in the cohort; the remaining four patients transferred to another maternity unit. Of the 42 live births, 27 (64%) were born by spontaneous vaginal delivery (SVD) and 15 (36%) by caesarean section (four elective; 11 emergency).

In the UK, parliament was to legalize physician assisted suicide in December 1997 when a private bill, ‘Doctor Assisted Dying’ was presented VX-809 datasheet by MP Joe Ashton which gained little publicity. The debate continues and there are several organizations seeking public support to legalize euthanasia and PAS. There have been some studies into the views of the medical and nursing profession towards these issues with little involvement

of pharmacists. Considering the diversifying role of the pharmacist and increasing contribution to palliative care, patient safety and medicines use, their input and subsequently attitudes to these practices warrants attention. A questionnaire adapted from Belnacasan purchase literature1 was administered to the level 4 MPharm cohort that investigated their views

on PAS. Students were asked to anonymously rate answers to questions about moral responsibility, personal beliefs, changes in the law and ethical guidance using a Likert scale, i.e. from 1 to 5, where 1 = strongly agree and 5 = strongly disagree . This was followed up by a focus group of a sample of 8 students selected conveniently to explore comments and issues that were found. Transcripts of the focus group were analysed by thematic analysis and constant comparison. Ethics was granted by the Ethics Committee of the University undertaking this research. 93 questionnaires were returned (53% response rate). There was a general consensus (median Mirabegron score 1, interquartile range (IQR) 1–3, 81%, n = 75) that a patient had the right to choose his/her death, and that assistance from their physician should be

allowed (median score 1, IQR 1–3, 72% n = 67). However, the use of prescription medicines to achieve premature death was not as acceptable with 52% (n = 48) disagreeing or strongly disagreeing (median score 4, IQR 2–5) and a further 26% (n = 24) unsure of their use for PAS. 40% agreed or strongly agreed (median score 2.5, IQR 1–5, n = 37) to the moral responsibility of the pharmacist to dispense medication for the purpose of PAS, but 78% agreed or strongly agreed (median score 2, IQR 1–4, n = 73) that legislation is required to regulate the practice appropriately, and specifically the GPhC should provide guidance to pharmacists on appropriate protocol for PAS (73%). Students (73%, n = 68) also claimed an encompassing statement within the conscience clause should allow pharmacists to abstain from involvement in this practice. This undergraduate cohort agrees that the practice of PAS should be accepted and legalised within the UK. However, despite agreeing that physicians have a role to play in this, the role of the pharmacist is less clear, with dispensing of medication for the use of PAS not generally accepted.

Grade 3–4 neutropenia was seen in 75% of patients,

with six episodes of grade 3–4 infection. Of note, only two patients received HAART during chemotherapy, three patients received zidovudine monotherapy and G-CSF was optional, given in only 54% of the cycles; all these factors most selleck chemicals llc likely contributing to the very significant toxicity reported in this study [44]. In contrast, in the above-mentioned stage-adapted study, 94% of patients received HAART during chemotherapy and G-CSF was recommended in all those receiving BEACOPP. Patients with early unfavourable HL (13% of the study population) received BEACOPP x4 or ABVD x4 + 30 Gy IF-RT, whereas those with advanced stage received BEACOPP x6–8. The CR/CRu rate was 100% and 86% for the early-unfavourable and the advanced-stage groups, respectively, and the 2-year PFS was 88% for both groups. Treatment-related mortality was 0% in the early-unfavourable group and 6% in the advanced-stage group [36]. We recommend for early-favourable HL: ABVD x2–4 + IFRT 20–30 Gy (level of evidence 1B). We recommend

for early-unfavourable HL: ABVD x4 + IFRT 30 Gy (level of evidence 1B). We recommend for advanced-stage HL: ABVD x6–8 +/− RT (level of evidence 1B). Prior to HAART, the prognosis CX-5461 of HIV-HL was significantly worse than that of the HIV-negative population with reduced CR rates ranging from 44 to 65% [45–47] and median OS of about 18 months. Since HAART, the outcomes for patients with HIV-HL have dramatically improved with CR rates Methocarbamol of 70–80% and EFS that are similar to the HIV-negative population [17,19]. Moreover, in recent studies, 5-year OS rates approach that of the HIV-negative population [17–19]. Higher CD4 cell counts, HL stage appropriate therapy and HAART are key factors that correlate with these improved outcomes [48]. Although HAART and ABVD can be safely co-administered [17–19], patients remain at increased risk for treatment-related toxicities [19]. Similarly, drug–drug interactions

between chemotherapy and specific types of HAART may drive adverse outcomes [19,49–52]. Clinically important adverse events such as additive vinblastine-mediated neurotoxicity and neutropenia in the presence of ritonavir have been described [49,50]. Some of these adverse events, such as increased neutropenia, can cause delays in the chemotherapy schedule thereby compromising CR rates [50]. We recommend patients should receive HAART during chemotherapy (level of evidence 1A). We recommend to avoid PI/ritonavir-boosted regimens (level of evidence 1D). Once again the addition of rituximab to ABVD chemotherapy has been explored mostly in the setting of immunocompetent patients, with no studies in people living with HIV. Rituximab has demonstrated single-agent activity in HL, in spite of the fact that only 20–30% of classical HL expresses CD20.

[98] During RA, chemical mediators in inflamed tissue invade and destroy cartilage and bone. The tissue pathological expansion, invasion and expression of growth factors, cytokines and hypoxic microenvironment which are a feature Veliparib solubility dmso of RA have resulted in the hypothesis that angiogenesis inhibition may be useful in the treatment of RA.[99] Disruption of the new vessel formation would not only prevent delivery of nutrients to the inflammatory site, but could also result in vessel regression and possibly reversal of disease.

There are several specific and non-specific angiogenesis inhibitors that have been FDA-approved or are currently being assessed in clinical trials which are safe for humans usage; however, their effects on RA remain untested.[100] The first line of angiostatic agents includes antagonists of VEGF, Ang and αvβ3 integrin and also non-specific angiogenesis inhibitors, including traditional disease-modifying anti rheumatic drugs (DMARDs), anti-TNF biologics, endostatin, angiostatin, fumagillin analogues or thalidomide.[101] However, their adverse effects (other than anti-TNF therapy) such as increased aminotransferase levels, hypertension, congestive heart failure, gastro-intestinal perforation, Idelalisib neutropenia, increased risk of serious infections, variations

in the gammaglobulin profile and high cost are major concerns.[16, 102] These drugs include anti-VEGF neutralizing BCKDHA monoclonal antibodies (bevacizumab), anti-sense VEGF cDNA, chimeric proteins consisting of the extracellular domain of VEGFR-1 and VEGFR-2 joined to the Fc portion of IgG, soluble VEGFRs, adenoviral expression of soluble VEGFRs and molecules that act through the inhibition of VEGF signaling.[103-106] In tumor research, VEGF signaling inhibitors stop angiogenesis

and destroy or change tumor vessels. Inhibition of VEGF and its receptors causes the loss of endothelial fenestrations, regression of tumor vessels and decrease in diameter, permeability and inflection of tumor vessels.[107, 108] Considering the important role of VEGF/VEGFR in regulating vascular function in RA, inhibitors of VEGF signaling could be beneficial. Norisoboldine (NOR), administered orally, significantly reduced the number of blood vessels and expression of growth factors in the synovium of adjuvant-induced arthritis (AIA) rats. NOR is able to stop synovial angiogenesis, which could be a supposedly new mechanism responsible for its anti-rheumatoid effect. The anti-angiogenesis activity of NOR was possibly achieved by decreasing the Notch-1 pathway-related endothelial tip cell phenotype with potential action of Notch-1 transcription complex.[109] In a recent study, Wei et al. suggest that NOR can also alleviate joint destruction in AIA rats by reducing RANKL, IL-6, PGE2, and MMP-13 expression via the p38/ERK/AKT/AP-1 pathway.

As expected, MALDI-TOF MS showed that SapB was not secreted by ramR or ramS mutant strains, irrespective of medium composition, whereas the wild-type strain secreted SapB in R5 medium, but not in the case of minimal mannitol medium (Fig. 1f). Taken together, these data show that SapB is unconditionally secreted by aerial hyphae of the wild type, whereas secretion of SapB by vegetative hyphae depends on medium composition. Previously, the existence of a regulatory mechanism called the sky pathway was proposed that operates after the bld cascade to control expression of aerial hyphae-specific genes such as those encoding the rodlins, chaplins, and

NepA (Claessen et al., 2004, 2006; de Jong et al., 2009). We propose that SapB production KU-57788 ic50 by vegetative hyphae is under the control of the bld cascade, while the sky pathway controls production of SapB by aerial structures. The fact that SapB is produced by aerial hyphae after their emergence infers an additional, yet

elusive role, during the later stages of morphological differentiation. Perhaps SapB contributes to spore wall assembly providing protection to the spores. Alternatively, it could contribute to providing a hydrated compartment involved in transport of nutrients up into the air, as suggested previously (Chater & Chandra, 2006; Chater Natural Product Library cost et al., 2010). Complete media used for growing S. coelicolor, such as R2YE or R5 medium, contain 10.3% sucrose, which is absent in minimal mannitol medium. We here addressed whether the presence of this sugar causes the SapB-dependent differentiation. To this end, the wild-type strain and the ramR and ramS strains were grown on minimal mannitol medium with or without 10.3% sucrose. In the absence of 10.3% sucrose, all mutant strains developed like the wild type (Fig. 2a). In contrast, sucrose strongly delayed development of the ramR and ramS mutants (Fig. 2b). This indicates that SapB has a direct or indirect role in formation of aerial hyphae under this condition.

In agreement, MALDI-TOF MS showed that SapB was present in the culture medium of the wild-type strain when the Fludarabine purchase medium was supplemented with 10.3% sucrose (Fig. 2d). To study the effect of sucrose on the interfacial surface tension, the pendant droplet technique was used, which is based on the geometry of a droplet (Thiessen & Man, 1999; Claessen et al., 2003; Sawyer et al., 2011). These data showed that 10.3% sucrose hardly, if at all, reduced the surface tension of R5 medium (values with or without sucrose: 66 ± 1.2 and 64 ± 1.1 mJ m−2, respectively) and minimal mannitol medium (73 ± 1.8 and 70 ± 1.4 mJ m−2, respectively). Moreover, sucrose did not alter the capacity of chaplins to assemble at the medium-air interface as was assessed by measuring ThT fluorescence (data not shown). These data indicate that the effect of sucrose is exerted, directly or indirectly, via a reduced turgor pressure in the hyphae.

This project was partly funded by The Danish Council for Independent Research (grant no. 10-093725). We thank Bodil Madsen for excellent technical assistance. “
“The temporal and cell density-dependent regulation of expression of virtually all the Staphylococcus aureus virulon is under the control of the agr (accessory gene regulatory) operon. The expression of the agr

operon is subject to transcriptional regulation by the AgrA/C two-component response regulator/sensor kinase pair. During bacteraemia, a frequent syndrome caused by methicillin-resistant S. aureus (MRSA), the transcriptional downregulation of agr expression has been attributed to the sequestration of the quorum-signalling molecule auto-inducing peptide (AIP) by the human serum component apolipoprotein B as part of an innate immune response to infection. However, it is not known whether click here transcriptional downregulation Inhibitor Library cell assay of agr expression during growth in human serum is additionally subjected to regulation by transcription regulatory proteins that either directly or indirectly affect transcription from the agr operon promoters. Here, using chromosomal fluorescence reporters of agr expression in

S. aureus, we show that the transcriptional downregulation of agr expression in human serum can be overcome using constitutive active mutant forms of AgrC. Therefore, it seems that the sequestration of the AIP is likely to be the only mechanism by which the host innate immune response limits agr expression at the transcriptional level to maintain the host–pathogen balance towards a noninvasive outcome. “
“Tenacibaculum maritimum (formerly Flexibacter maritimus) is a filamentous, biofilm-forming member of the Cytophaga–Flavobacterium–Bacteroides group (or Bacteroidetes), which causes the widely distributed marine fish disease tenacibaculosis. A search for N-acylhomoserine lactones (AHLs) quorum-sensing (QS)

signals in the culture media of nine representative strains of this species using different biosensor strains revealed the presence of short-type AHL activity in all of them. N-butyryl-l-homoserine lactone (C4-HSL) was identified in T. maritimum NCIMB2154T by LC-MS. A degradation activity for long-acyl AHLs (C10-HSL) Niclosamide was subsequently demonstrated in T. maritimum NCIMB2154T. The acidification of the culture medium after degradation did not allow the recovery of C10-HSL, which indicates a possible acylase-type degradation activity. Even though the physiological processes under the control of AHL-mediated QS in T. maritimum need to be further characterized, this discovery extends the paradigm of AHL-mediated QS signalling beyond the Proteobacteria and reinforces its ecological significance. Many bacterial species coordinate responses to environmental changes using complex cell–cell communication mechanisms in a cell-density-dependent manner.

Asymptomatic people who have an estimated selleckchem multifactorial CVD risk >20% over 10 years.

People with diabetes mellitus (type 1 or 2). People with elevated blood pressure >160 mmHg systolic or >100 mmHg diastolic, or lesser degrees of blood pressure elevation with target organ damage. People with elevated total cholesterol to high-density lipoprotein cholesterol ratio >6.0. People with familial dyslipidaemia. NICE does not recommend a specific CVD risk calculation for the UK population [186]. Cohort data have demonstrated that the observed myocardial infarction (MI) rates in HIV-seropositive people in developed countries paralleled those predicted by the Framingham risk equation [187] but the extent to which this can be extrapolated to women and men of non-European ethnicity is unknown. Therefore, there is insufficient evidence to recommend a specific CVD risk calculation for the population of HIV-positive adults in UK. The Framingham CVD risk calculator works reasonably well in HIV-positive populations, although it is worth noting that it was not developed for use in non-white find more groups. Other

algorithms may be better suited to these populations. A CVD risk calculator has been developed for use in HIV-positive populations (http://www.chip.dk/TOOLS) [188], although it should be noted that this provides 5-year risk estimates rather than the usual 10-year estimates. Alternatively, the QRISK calculator (http://www.qrisk.org) or the QIntervention tool (http://qintervention.org), which also provides an estimate of the risk of developing type II diabetes, can be used. There are insufficient data to inform whether CVD risk should affect the decision to start ART. The SMART trial provides the only randomized data about the effect of ART on CVD risk, but was not powered for a CVD endpoint. Fewer major CVD events were observed in the viral suppression arm but the difference was not statistically significant [189]. In a post hoc analysis, HIV VL <400 copies/mL was associated with fewer CVD events

suggesting that suppression of viraemia may have been protective; CD4 cell count was not significantly associated with CVD events [190, 191]. Several cohort studies have examined changes in rate of cardiovascular events in HIV-positive populations over time since the heptaminol introduction of ART but no clear protective effect was found [192-195]. In the HIV Outpatients Study cohort, baseline CD4 cell count <350 cells/μL was associated with increased CVD risk, but 350–500 cells/μL and use of ART were not; in a parallel case–control study, cases were more likely to have a current (but not baseline or nadir) CD4 cell count of 350–500 cells/μL [196]. The Data Collection on Adverse events of Anti-HIV Drugs (D:A:D) study found that untreated patients had a lower incidence of MI than those on ART [197] and risk increased with longer exposure to combination therapy [198].

Similar results have been obtained for the binding sites of Rhodobacter sphaeroides PrrA (Eraso & Kaplan, 2009) and Vibrio fischeri LuxR (Antunes et al., 2008). Like the C24T mutation, transitions (pyrimidine–pyrimidine and purine–purine substitutions) often had less severe effects than transversions (pyrimidine–purine and purine–pyrimidine RO4929097 substitutions), suggesting that the respective nucleotides are not exclusively involved in direct interactions with a regulator, but in addition, influence promoter topology. (6) Thymidine 21 is invariant

in all R. capsulatus Mo-boxes (Fig. 1a), suggesting its importance for Mo-dependent regulation. Surprisingly, mutation T21C neither abolished Mo repression of anfA (Fig. 2c) nor binding by MopA and MopB (Fig. 3). In contrast to T21C, substitution of key nucleotides in other cis-regulatory elements often abolishes binding of the respective regulators including Salmonella typhimurium MetR (Byerly et al., 1991), Pseudomonas aeruginosa VqsR (Li et al., 2007), or Bacillus subtilis CAP (Weickert & Chambliss, 1990). Thus, we conclude that the anfA-Mo-box is a highly flexible regulator-binding site that even tolerates the substitution of a conserved nucleotide. (7) As expected, the JAK inhibitor anfAmop hybrid promoter was not bound by MopB (Fig. 3). Unexpectedly, however, binding by MopA was also (almost) completely abolished. Expression of the hybrid

promoter was no longer Mo regulated Sinomenine and threefold lower as compared with the expression of the wild-type promoter under derepressing conditions (Fig. 2a and c). This finding suggests that the interplay between anfA-Mo-box and flanking sequences is important for proper binding of RNA polymerase. (8) Consistent with the previously shown redundant function of MopA and MopB on anfA regulation (Wiethaus et al., 2006), all anfA-Mo-box mutations

analyzed in this study equally affected regulation and binding by both regulators, MopA and MopB (Figs 2 and 3). As outlined above for the Mo-repressed anfA-Mo-box, the effects of mutations on the Mo-activated mop-Mo-box were analyzed by lacZ reporter fusions (Fig. 4) and DNA mobility shift assays (Fig. 5). The effects of Mo-box mutations on mop gene activation and regulator binding may be summarized as follows. (1) The wild-type mop promoter was activated in the R. capsulatus wild-type background (column 1) and in the mopB mutant strain (column 3). No expression was observed in strains defective for mopA (Fig. 4b; columns 2 and 4), thus confirming that mop activation strictly depends on MopA (Wiethaus et al., 2006, 2009). Accordingly, MopA weakly shifted the wild-type mop promoter, while MopB did not bind the mop promoter at all (Fig. 5). As observed earlier (Wiethaus et al., 2006), gel shifts with the mop promoter did not produce distinct shifted bands, suggesting that promoter–activator complexes were disrupted during gel electrophoresis.

The analysis of the organization of the genes involved in the conjugative transfer of the plasmids from sphingomonads

suggested that these genes are inherited independently from the rep/par systems. This was also SAHA HDAC datasheet confirmed by sequence comparisons between the genes encoding the pilins (traA, trbC or virB2), pore-forming proteins from the outer membrane (traL, trbD or virB3) or the coupling proteins (traD, traG or virD4). Thus, it was found that according to the pilins, the conjugative systems can be clearly separated as the pilins from plasmids pCAR3, pNL1 (‘Mega-RepAC’), pISP1 (‘Mega-RPA’), pLA1 and pSWIT01 (‘Mega-Rep3’) consist of 247–262 aa. In contrast, the pilins from plasmids pSWIT02 (‘Mega-RepAC’), pCHQ1, pSLPG, pSPHCH01, pISP0 (‘Mega-Rep3’) and pLA2 are composed

of only 100–115 amino acids. This difference resulted in the respective phylogenetic trees Cobimetinib mouse in the formation of two clearly separated branches (Fig. 4a). Rather similar phylogenetic trees are also obtained for the comparisons of the pore-forming proteins and the coupling proteins (Fig. 4b and c). The ‘degradative megaplasmids’ from sphingomonads can be differentiated according to their rep and par genes into three major groups, which presumably represent different incompatibility groups. The DNA sequences suggest that most of these plasmids are conjugative and that Amisulpride the transfer functions evolve largely independently from the respective plasmid replication systems. The rep/par- and tra/vir-systems of these plasmids are clearly homologous to isofunctional systems found in other Gram-negative bacteria. This suggests that factors independent of the basic functions of plasmid transfer and maintenance are responsible for the specific occurrence of these ‘megaplasmids’ among the sphingomonads. A possible explanation for

the restricted transfer of these plasmids to other bacterial groups might be related to the specific prevalence of sphingolipids in the outer membranes of sphingomonads, which might interfere with the conjugative transfer of plasmid DNA to nonsphingomonads. “
“Paddy rice has been of particular interest as a forage crop in Japan. In this study, the isolated strains TO1000, TO1001, TO1002, and TO1003 were characterized by phenotypic and genotypic approaches. These strains were identified as Lactobacillus plantarum subsp. plantarum by species-specific PCR. Phenotypic characteristics varied among different strains of the same subspecies, and the strains represented unique and diverse phenotypes related to fermentation factors, such as carbohydrate assimilation and range of pH and temperature allowing growth. PCR analysis revealed that the patterns of presence/absence of known plantaricin genes differed in a strain-specific manner.

[1,18,19] Integration of electronic prescribing in hospital, community and aged-care settings has been trialled, and national implementation, in line with the development

GSK2118436 datasheet of national electronic health records, is currently under review.[20] However, the implementation of electronic prescribing requires training for healthcare staff, funding, technological resources and compatibility with the existing medication recording system,[1,19,20] limiting the potential for expansion in rural areas. Relevant exploratory research for implementation in rural areas is lacking. It is crucial to review medication orders or prescriptions for compliance with legislative or PBS requirements and clinical appropriateness prior to supply or administration of the medication, a task commonly undertaken by pharmacists. The Regulation specifies that pharmacists must follow Quality CHIR-99021 order Standards during dispensing of medications to consumers (section 4A).[5] The standards that apply are the Pharmaceutical Society of Australia (PSA) Professional Practice Standards.[21] Specifically, the pharmacist should review the medication order by considering the patient’s medication history, drug interactions or appropriateness of dosing regimen when dispensing the prescribed medication.[2,21,22] Studies have shown that the support from a pharmacist in reviewing prescribing decisions is perceived

by prescribers as valuable.[19,23–25] Electronic transfer of prescriptions (under development

in Australia) has integrated computer-based Selleckchem Baf-A1 clinical decision-support systems for checking of the patient’s medication history for interactions, allergies and duplicate ordering, to enhance appropriate prescribing and patient safety.[1,8,19,26] Although studies exploring such systems have been limited to certain settings or institutions,[1,26] the implementation of nationwide electronic health records will allow a consistent and complete set of patients’ medication records to improve provision of healthcare.[20] While the benefits of support systems in assisting with prescribing have been reported, some of the shortcomings identified in the literature were blocking features for privacy, excessive or inappropriate alerting systems and variability or inconsistencies across products.[1,19,20] Although research and evidence is lacking in terms of the superiority of computerised systems as opposed to pharmacotherapeutic knowledge of an actual healthcare provider, such as a pharmacist, adjunct use of such support systems has the potential to improve the process of reviewing medication orders. No reports were identified involving non-pharmacists’ review of prescribing decisions in a rural setting, although nursing staff were reported to perform occasional clarification of medication orders.