The impact of a closed-loop electronic prescribing and automated dispensing system on the ward pharmacist’s time and activities

Objective To assess the impact of a closed-loop electronic prescribing and automated dispensing system on the time spent providing a ward pharmacy service and the activities carried out. Setting Surgical ward, London teaching hospital. Method All data were collected two months pre- and one year post-intervention. First, the ward pharmacist recorded the time taken each day for four weeks. Second, an observational study was conducted over 10 weekdays, using two-dimensional work sampling, to identify the ward pharmacist's activities. Finally, medication orders were examined to identify pharmacists' endorsements that should have been, and were actually, made. Key findings Mean time to provide a weekday ward pharmacy service increased from 1 h 8 min to 1 h 38 min per day (P = 0.001; unpaired t-test). There were significant increases in time spent prescription monitoring, recommending changes in therapy/monitoring, giving advice or information, and non-productive time. There were decreases for supply, looking for charts and checking patients' own drugs. There was an increase in the amount of time spent with medical and pharmacy staff, and with 'self'. Seventy-eight per cent of patients' medication records could be assessed for endorsements pre- and 100% post-intervention. Endorsements were required for 390 (50%) of 787 medication orders pre-intervention and 190 (21%) of 897 afterwards (P < 0.0001; chi-square test). Endorsements were made for 214 (55%) of endorsement opportunities pre-intervention and 57 (30%) afterwards (P < 0.0001; chi-square test). Conclusion The intervention increased the overall time required to provide a ward pharmacy service and changed the types of activity undertaken. Contact time with medical and pharmacy staff increased. There was no significant change in time spent with patients. Fewer pharmacy endorsements were required post-intervention, but a lower percentage were actually made. The findings have important implications for the design, introduction and use of similar systems.

Holocene vegetation dynamics in the northeastern Rub' al-Khali desert, Arabian Peninsula: a phytolith, pollen and carbon isotope study

The Holocene vegetation history of the Arabian Peninsula is poorly understood, with few palaeobotanical studies to date. At Awafi, Ras al-Khaimah, UAE, a 3.3 m lake sediment sequence records the vegetation development for the period 8500 cal. yr BP to similar to3000 cal. yr BP. delta(13)C isotope, pollen and phytolith analyses indicate that C3 Pooid grassland with a strong woody element existed during the early Holocene (between 8500 and 6000 cal. yr BP) and became replaced by mixed C3 and C4 grasses with a strong C4 Panicoid tall grass element between 5900 and 5400 cal. yr BP. An intense, arid event Occurred at 4100 cal. yr BP when the lake desiccated and was infilled by Aeolian sand. From 4100 cal. yr BP the vegetation was dominated by C4 Chloridoid types and Cyperaceae, suggesting an incomplete vegetation cover and Aeolian dune reactivation owing to increased regional aridity. These data outline the ecosystem dynamics and carbon cycling in response to palaeomon-soon and north-westerly variability during the Holocene. Copyright (C) 2004 John Wiley Sons, Ltd.

The effects of electronic prescribing on the quality of prescribing

Aims To investigate the effects of electronic prescribing (EP) on prescribing quality, as indicated by prescribing errors and pharmacists' clinical interventions, in a UK hospital. Methods Prescribing errors and pharmacists' interventions were recorded by the ward pharmacist during a 4 week period both pre- and post-EP, with a second check by the principal investigator. The percentage of new medication orders with a prescribing error and/or pharmacist's intervention was calculated for each study period. Results Following the introduction of EP, there was a significant reduction in both pharmacists' interventions and prescribing errors. Interventions reduced from 73 (3.0% of all medication orders) to 45 (1.9%) (95% confidence interval (CI) for the absolute reduction 0.2, 2.0%), and errors from 94 (3.8%) to 48 (2.0%) (95% CI 0.9, 2.7%). Ten EP-specific prescribing errors were identified. Only 52% of pharmacists' interventions related to a prescribing error pre-EP, and 60% post-EP; only 40% and 56% of prescribing errors resulted in an intervention pre- and post-EP, respectively. Conclusions EP improved the quality of prescribing by reducing both prescribing errors and pharmacists' clinical interventions. Prescribers and pharmacists need to be aware of new types of error with EP, so that they can best target their activities to reduce clinical risk. Pharmacists may need to change the way they work to complement, rather than duplicate, the benefits of EP.

The impact of a closed-loop electronic prescribing and administration system on prescribing errors, administration errors and staff time: a before-and-after study

Objectives: To assess the impact of a closed-loop electronic prescribing, automated dispensing, barcode patient identification and electronic medication administration record (EMAR) system on prescribing and administration errors, confirmation of patient identity before administration, and staff time. Design, setting and participants: Before-and-after study in a surgical ward of a teaching hospital, involving patients and staff of that ward. Intervention: Closed-loop electronic prescribing, automated dispensing, barcode patient identification and EMAR system. Main outcome measures: Percentage of new medication orders with a prescribing error, percentage of doses with medication administration errors (MAEs) and percentage given without checking patient identity. Time spent prescribing and providing a ward pharmacy service. Nursing time on medication tasks. Results: Prescribing errors were identified in 3.8% of 2450 medication orders pre-intervention and 2.0% of 2353 orders afterwards (p<0.001; χ2 test). MAEs occurred in 7.0% of 1473 non-intravenous doses pre-intervention and 4.3% of 1139 afterwards (p = 0.005; χ2 test). Patient identity was not checked for 82.6% of 1344 doses pre-intervention and 18.9% of 1291 afterwards (p<0.001; χ2 test). Medical staff required 15 s to prescribe a regular inpatient drug pre-intervention and 39 s afterwards (p = 0.03; t test). Time spent providing a ward pharmacy service increased from 68 min to 98 min each weekday (p = 0.001; t test); 22% of drug charts were unavailable pre-intervention. Time per drug administration round decreased from 50 min to 40 min (p = 0.006; t test); nursing time on medication tasks outside of drug rounds increased from 21.1% to 28.7% (p = 0.006; χ2 test). Conclusions: A closed-loop electronic prescribing, dispensing and barcode patient identification system reduced prescribing errors and MAEs, and increased confirmation of patient identity before administration. Time spent on medication-related tasks increased.

Iron Uptake and Homeostasis in Microorganisms

Preface. Iron is considered to be a minor element employed, in a variety of forms, by nearly all living organisms. In some cases, it is utilised in large quantities, for instance for the formation of magnetosomes within magnetotactic bacteria or during use of iron as a respiratory donor or acceptor by iron oxidising or reducing bacteria. However, in most cases the role of iron is restricted to its use as a cofactor or prosthetic group assisting the biological activity of many different types of protein. The key metabolic processes that are dependent on iron as a cofactor are numerous; they include respiration, light harvesting, nitrogen fixation, the Krebs cycle, redox stress resistance, amino acid synthesis and oxygen transport. Indeed, it is clear that Life in its current form would be impossible in the absence of iron. One of the main reasons for the reliance of Life upon this metal is the ability of iron to exist in multiple redox states, in particular the relatively stable ferrous (Fe2+) and ferric (Fe3+) forms. The availability of these stable oxidation states allows iron to engage in redox reactions over a wide range of midpoint potentials, depending on the coordination environment, making it an extremely adaptable mediator of electron exchange processes. Iron is also one of the most common elements within the Earth’s crust (5% abundance) and thus is considered to have been readily available when Life evolved on our early, anaerobic planet. However, as oxygen accumulated (the ‘Great oxidation event’) within the atmosphere some 2.4 billion years ago, and as the oceans became less acidic, the iron within primordial oceans was converted from its soluble reduced form to its weakly-soluble oxidised ferric form, which precipitated (~1.8 billion years ago) to form the ‘banded iron formations’ (BIFs) observed today in Precambrian sedimentary rocks around the world. These BIFs provide a geological record marking a transition point away from the ancient anaerobic world towards modern aerobic Earth. They also indicate a period over which the bio-availability of iron shifted from abundance to limitation, a condition that extends to the modern day. Thus, it is considered likely that the vast majority of extant organisms face the common problem of securing sufficient iron from their environment – a problem that Life on Earth has had to cope with for some 2 billion years. This struggle for iron is exemplified by the competition for this metal amongst co-habiting microorganisms who resort to stealing (pirating) each others iron supplies! The reliance of micro-organisms upon iron can be disadvantageous to them, and to our innate immune system it represents a chink in the microbial armour, offering an opportunity that can be exploited to ward off pathogenic invaders. In order to infect body tissues and cause disease, pathogens must secure all their iron from the host. To fight such infections, the host specifically withdraws available iron through the action of various iron depleting processes (e.g. the release of lactoferrin and lipocalin-2) – this represents an important strategy in our defence against disease. However, pathogens are frequently able to deploy iron acquisition systems that target host iron sources such as transferrin, lactoferrin and hemoproteins, and thus counteract the iron-withdrawal approaches of the host. Inactivation of such host-targeting iron-uptake systems often attenuates the pathogenicity of the invading microbe, illustrating the importance of ‘the battle for iron’ in the infection process. The role of iron sequestration systems in facilitating microbial infections has been a major driving force in research aimed at unravelling the complexities of microbial iron transport processes. But also, the intricacy of such systems offers a challenge that stimulates the curiosity. One such challenge is to understand how balanced levels of free iron within the cytosol are achieved in a way that avoids toxicity whilst providing sufficient levels for metabolic purposes – this is a requirement that all organisms have to meet. Although the systems involved in achieving this balance can be highly variable amongst different microorganisms, the overall strategy is common. On a coarse level, the homeostatic control of cellular iron is maintained through strict control of the uptake, storage and utilisation of available iron, and is co-ordinated by integrated iron-regulatory networks. However, much yet remains to be discovered concerning the fine details of these different iron regulatory processes. As already indicated, perhaps the most difficult task in maintaining iron homeostasis is simply the procurement of sufficient iron from external sources. The importance of this problem is demonstrated by the plethora of distinct iron transporters often found within a single bacterium, each targeting different forms (complex or redox state) of iron or a different environmental condition. Thus, microbes devote considerable cellular resource to securing iron from their surroundings, reflecting how successful acquisition of iron can be crucial in the competition for survival. The aim of this book is provide the reader with an overview of iron transport processes within a range of microorganisms and to provide an indication of how microbial iron levels are controlled. This aim is promoted through the inclusion of expert reviews on several well studied examples that illustrate the current state of play concerning our comprehension of how iron is translocated into the bacterial (or fungal) cell and how iron homeostasis is controlled within microbes. The first two chapters (1-2) consider the general properties of microbial iron-chelating compounds (known as ‘siderophores’), and the mechanisms used by bacteria to acquire haem and utilise it as an iron source. The following twelve chapters (3-14) focus on specific types of microorganism that are of key interest, covering both an array of pathogens for humans, animals and plants (e.g. species of Bordetella, Shigella, , Erwinia, Vibrio, Aeromonas, Francisella, Campylobacter and Staphylococci, and EHEC) as well as a number of prominent non-pathogens (e.g. the rhizobia, E. coli K-12, Bacteroides spp., cyanobacteria, Bacillus spp. and yeasts). The chapters relay the common themes in microbial iron uptake approaches (e.g. the use of siderophores, TonB-dependent transporters, and ABC transport systems), but also highlight many distinctions (such as use of different types iron regulator and the impact of the presence/absence of a cell wall) in the strategies employed. We hope that those both within and outside the field will find this book useful, stimulating and interesting. We intend that it will provide a source for reference that will assist relevant researchers and provide an entry point for those initiating their studies within this subject. Finally, it is important that we acknowledge and thank wholeheartedly the many contributors who have provided the 14 excellent chapters from which this book is composed. Without their considerable efforts, this book, and the understanding that it relays, would not have been possible. Simon C Andrews and Pierre Cornelis

Phytoestrogen consumption and association with breast, prostate and colorectal cancer in EPIC Norfolk

Phytoestrogens are polyphenolic secondary plant metabolites that have structural and functional similarities to 17β-oestradiol and have been associated with a protective effect against hormone-related cancers. Most foods in the UK only contain small amounts of phytoestrogens (median content 21 μg/100 g) and the highest content is found in soya and soya-containing foods. The highest phytoestrogen content in commonly consumed foods is found in breads (average content 450 μg/100 g), the main source of isoflavones in the UK diet. The phytoestrogen consumption in cases and controls was considerably lower than in Asian countries. No significant associations between phytoestrogen intake and breast cancer risk in a nested case-control study in EPIC Norfolk were found. Conversely, colorectal cancer risk was inversely associated with enterolignan intake in women but not in men. Prostate cancer risk was positively associated with enterolignan intake, however this association became non-significant when adjusting for dairy intake, suggesting that enterolignans can act as a surrogate marker for dairy or calcium intake.

The role of weeds in supporting biological diversity within crop fields

Weeds are major constraints on crop production, yet as part of the primary producers within farming systems, they may be important components of the agroecosystem. Using published literature, the role of weeds in arable systems for other above-ground trophic levels are examined. In the UK, there is evidence that weed flora have changed over the past century, with some species declining in abundance, whereas others have increased. There is also some evidence for a decline in the size of arable weed seedbanks. Some of these changes reflect improved agricultural efficiency, changes to more winter-sown crops in arable rotations and the use of more broad-spectrum herbicide combinations. Interrogation of a database of records of phytophagous insects associated with plant species in the UK reveals that many arable weed species support a high diversity of insect species. Reductions in abundances of host plants may affect associated insects and other taxa. A number of insect groups and farmland birds have shown marked population declines over the past 30 years. Correlational studies indicate that many of these declines are associated with changes in agricultural practices. Certainly reductions in food availability in winter and for nestling birds in spring are implicated in the declines of several bird species, notably the grey partridge, Perdix perdix . Thus weeds have a role within agroecosystems in supporting biodiversity more generally. An understanding of weed competitivity and the importance of weeds for insects and birds may allow the identification of the most important weed species. This may form the first step in balancing the needs for weed control with the requirements for biodiversity and more sustainable production methods.

Sterol content analysis suggests altered eburicol 14 alpha-demethylase (CYP51) activity in isolates of Mycosphaerella graminicola adapted to azole fungicides

The recent decline in the effectiveness of some azole fungicides in controlling the wheat pathogen Mycosphaerella graminicola has been associated with mutations in the CYP51 gene encoding the azole target, the eburicol 14 alpha-demethylase (CYP51), an essential enzyme of the ergosterol biosynthesis pathway. In this study, analysis of the sterol content of M. graminicola isolates carrying different variants of the CYP51 gene has revealed quantitative differences in sterol intermediates, particularly the CYP51 substrate eburicol. Together with CYP51 gene expression studies, these data suggest that mutations in the CYP51 gene impact on the activity of the CYP51 protein.

A mathematical model of the in vitro keratinocyte response to chromium and nickel exposure

A mathematical model describing the main mechanistic processes involved in keratinocyte response to chromium and nickel has been developed and compared to experimental in vitro data. Accounting for the interactions between the metal ions and the keratinocytes, the law of mass action was used to generate ordinary differential equations which predict the time evolution and ion concentration dependency of keratinocyte viability, the amount of metal associated with the keratinocytes and the release of cytokines by the keratinocytes. Good agreement between model predictions and existing experimental data of these endpoints was observed, supporting the use of this model to explore physiochemical parameters that influence the toxicological response of keratinocytes to these two metals.

Application of real-time and multiplex PCR assays to study leaf blotch epidemics in barley

Leaf blotch, caused by Rhynchosporium secalis, was studied in a range of winter barley cultivars using a combination of traditional plant pathological techniques and newly developed multiplex and real-time polymerase chain reaction (PCR) assays. Using PCR, symptomless leaf blotch colonization was shown to occur throughout the growing season in the resistant winter barley cv. Leonie. The dynamics of colonization throughout the growing season were similar in both Leonie and Vertige, a susceptible cultivar. However, pathogen DNA levels were approximately 10-fold higher in the susceptible cultivar, which expressed symptoms throughout the growing season. Visual assessments and PCR also were used to determine levels of R. secalis colonization and infection in samples from a field experiment used to test a range of winter barley cultivars with different levels of leaf blotch resistance. The correlation between the PCR and visual assessment data was better at higher infection levels (R(2) = 0.81 for leaf samples with >0.3% disease). Although resistance ratings did not correlate well with levels of disease for all cultivars tested, low levels of infection were observed in the cultivar with the highest resistance rating and high levels of infection in the cultivar with the lowest resistance rating.

Timing and the holding periods of institutional real estate

Literature on investors' holding periods for securities suggests that high transaction costs are associated with longer holding periods. Return volatility, by contrast, is associated with shorter holding periods. In real estate, high transaction costs and illiquidity imply longer holding periods. Research on depreciation and obsolescence suggests that there might be an optimal holding period. Sales rates and holding periods for U.K. institutional real estate are analyzed, using a proportional hazards model, over an 18-year period. The results show longer holding periods than those claimed by investors, with marked differences by type of property and over time. The results shed light on investor behavior.

Peroxides in ordered nanoporous silicas: clean alternatives to transition metal oxidants for the removal of toxic gases

Ordered nano-structured MCM-48 silica containing sodium peroxydisulfate is a novel, highly effective material for the decomposition of HCN under ambient conditions.