Managed livestock grazing is compatible with the maintenance of plant diversity in semidesert grasslands.

Even when no baseline data are available, the impacts of 150 years of livestock grazing on natural grasslands can be assessed using a combined approach of grazing manipulation and regional-scale assessment of the flora. Here, we demonstrate the efficacy of this method across 18 sites in the semidesert Mitchell grasslands of northeastern Australia. Fifteen-year-old exclosures (ungrazed and macropod grazed) revealed that the dominant perennial grasses in the genus Astrebla do not respond negatively to grazing disturbance typical of commercial pastoralism. Neutral, positive, intermediate, and negative responses to grazing disturbance were recorded amongst plant species with no single life-form group associated with any response type. Only one exotic species, Cenchrus ciliaris, was recorded at low frequency. The strongest negative response was from a native annual grass, Chionachne hubbardiana, an example of a species that is highly sensitive to grazing disturbance. Herbarium records revealed only scant evidence that species with a negative response to grazing have declined through the period of commercial pastoralism. A regional analysis identified 14 from a total of 433 plant species in the regional flora that may be rare and potentially threatened by grazing disturbance. However, a targeted survey precluded grazing as a cause of decline for seven of these based on low palatability and positive responses to grazing and other disturbance. Our findings suggest that livestock grazing of semidesert grasslands with a short evolutionary history of ungulate grazing has altered plant composition, but has not caused declines in the dominant perennial grasses or in species richness as predicted by the preceding literature. The biggest impact of commercial pastoralism is the spread of woody leguminous trees that can transform grassland to thorny shrubland. The conservation of plant biodiversity is largely compatible with commercial pastoralism provided these woody weeds are controlled, but reserves strategically positioned within water remote areas are necessary to protect grazing-sensitive species. This study demonstrates that a combination of experimental studies and regional surveys can be used to understand anthropogenic impacts on natural ecosystems where reference habitat is not available.

Performance-based readability testing of participant materials for a phase I trial: TGN1412.

BACKGROUND: Concern has been expressed about the process of consent to clinical trials, particularly in phase I "first-in-man" trials. Trial participant information sheets are often lengthy and technical. Content-based readability testing of sheets, which is often required to obtain research ethics approval for trials in the USA, is limited and cannot indicate how information will perform. METHODS: An independent-groups design was used to study the user-testing performance of the participant information sheet from the phase I TGN1412 trial. Members of the public were asked to read it, then find and demonstrate understanding of 21 key aspects of the trial. The participant information sheet was then rewritten, redesigned and tested on 20 members of the public, using the same 21-item questionnaire. RESULTS: On the original TGN1412 participant information sheet, participants could not find answers and some of the found information was not understood. Six of 21 questions, including those relating to placebo, follow-up visits and the emergency phone number, were found by eight or fewer of 10 participants. The revised information sheet performed better, with the answers to 17 of 21 questions found and understood by all 20 participants. CONCLUSIONS: Tests showed that the TGN1412 participant information sheet may not inform participants adequately for consent. Revising its content and design led to significant improvements. Writers of materials for trial participants should take account of good practice in information design. Performance-based user testing may be a useful method to indicate strengths and weaknesses in trial materials.

Explanations for variations in clopidogrel prescribing in England.

BACKGROUND: The National Audit Office (NAO) has produced prescribing indicators that Primary Care Trusts (PCTs) can use to judge their performance. One of the indicators is for the antiplatelet clopidogrel, measured as defined daily dose (DDD) per cardiovascular Specific Therapeutic Age Related Prescribing Unit (STAR-PU). Clopidogrel is used as an indicator because it is a more expensive medicine than the alternative (aspirin) and there may be scope for cost reduction. We aimed to establish if the NAO indicator for clopidogrel prescribing is a valid measure of prescribing performance. METHODS: Prescribing data for 152 PCTs and a range of explanatory variables were obtained. Correlation between variables was determined. A regression analysis was conducted to compare the dependent variable (prescribing) with the explanatory variables identified. RESULTS: The percentage of patients on the coronary heart disease register and Index of Multiple Deprivation explained 30% of the variation in prescribing (DDD/STAR-PU) between PCTs. Even though DDD/STAR-PU is adjusted for age and sex other measures of need still have an impact on prescribing. CONCLUSIONS: Using DDD/STAR-PU alone as a prescribing indicator might misidentify some PCTs, which are under- and over-using clopidogrel. Poor ranking against other PCTs using the NAO indicator should be fully explored taking into account other variables (cardiovascular morbidity and deprivation) before any corrective action is taken.

In Search of Lost Springs: A Protocol for Locating Active and Inactive Springs.

Groundwater springs are significant landscape features for humans and the biota that occupies their habitat. Many springs become inactive where groundwater exploitation by humans has lowered the water table or artesian pressure. In order to assess this impact, it is important to identify and locate active, and with more difficulty, inactive springs. Using a variety of archival, environmental and field-based data, this study presents a protocol for the determination of the location and status of springs across the Great Artesian Basin of Australia. This protocol underpins a database of springs, which is not only important for the assessment of spring ecosystems, but also contributes to understand groundwater extraction impacts and hydrogeological processes. The database indicates that 30.0% of discharge (artesian) springs in the Great Artesian Basin are entirely inactive and another 11.8% are partially inactive. For the outcrop (gravity) springs of the Basin, only 1.9% are entirely inactive and 7.4% partially inactive, and for the outcrop springs in the Tertiary sandstone overlying the Basin 30.9% are inactive and 18.2% are partially inactive.

Detection of Norwalk virus in the UK by the polymerase chain reaction.

We have developed a polymerase chain reaction for the detection of Norwalk virus using the published sequence of the virus RNA dependent RNA polymerase gene and have used this to clone and sequence this region of a virus from a UK outbreak. We have applied this method to a panel of UK Norwalk-like viruses using both Tet-z and Taq DNA polymerases and found that amplification produces a multiplicity of bands from stool samples. However, in combination with Southern blotting, Taq polymerase amplification detected virus in 13 of a panel of 30 clinical samples known to contain these viruses and also detected astroviruses in a mixed infection. Amplification using Tet-z DNA polymerase was less efficient (6/30) and detected predominantly viruses typed as UK type 2 by solid phase immune electron microscopy.

The cost of medicines in the United Kingdom. A survey of general practitioners' opinions and knowledge.

Prescribing costs in general practice continue to grow. Their importance is underlined by the amount of information concerned with costs that general practitioners (GPs) receive, and by the existence of target budgets. In 1986 and 1991, surveys showed that GPs agreed that cost should be borne in mind when choosing medicines, but that their knowledge of drug prices was often inaccurate. This study assessed the current knowledge and attitudes of GPs in the UK in respect of prescribing costs, and examined the influence of various developments in general practice since 1986 on the accuracy of drug price estimation. 1000 randomly selected GP principals (500 in Scotland and 125 in each of 4 English health regions) were sent a postal questionnaire. The GPs' level of agreement with 5 statements concerned with prescribing costs, and the accuracy of their estimates of the basic price of 31 drugs, were analysed. Most GPs (71%) agreed that prescribing costs should be taken into account when deciding on the best treatment for patients. Fundholders were more likely than non-fundholders: (i) to agree that prescribing costs could be reduced without affecting patient care; (ii) to agree that providing more information on costs would lower the cost of prescribing; and (iii) to comment that cost guidelines had changed their prescribing habits. Fundholders were less likely than non-fundholders to reject the principle of fixed limits on prescribing costs. Overall, one-third of the price estimates given were accurate (within 25% of the actual cost). For the most expensive drugs in the survey [those priced over 10 pounds sterling (Pound) per pack], half of the price estimates were accurate. There were significant differences between non-fundholders' and fundholders' estimates of the price of less expensive drugs (those priced at less than 10 pounds per pack). Use of a formulary or computer-displayed drug price information did not affect the accuracy of price estimates. It may be that GPs who were more knowledgeable and concerned about costs were more likely to become fundholders. It is also possible that the expansion of fundholding, or other mechanisms that give GPs responsibility for resource allocation, might improve accurate cost awareness in prescribing. Clinical and economic review of repeat prescribing is recommended.

The 1990 GP contract--meeting needs?

This paper reviews the empirical evidence about the effects of the 1990 general practitioner (GP) contract on the provision of medical services in the United Kingdom. A brief outline of the major changes instigated by the 1990 GP contract is given. Studies of the implementation of the changes tend to focus on either trend analysis, cost-effectiveness or medical practice variation. These studies are reviewed and the implications for the efficiency of primary health care are discussed.

An economic evaluation of thrombolysis in a remote rural community.

OBJECTIVES: To assess the cost effectiveness of community thrombolysis relative to hospital thrombolysis by investigating the extra costs and benefits of a policy of community thrombolysis, then establishing the extra cost per life saved by community thrombolysis. DESIGN: Economic evaluation based on the results of the Grampian region early anistreplase trial. SETTING: 29 rural general practices and one secondary care provider in Grampian, Scotland. SUBJECTS: 311 patients recruited to the Grampian region early anistreplase trial. INTERVENTIONS: Intravenous anistreplase given either by general practitioners or secondary care clinicians. MAIN OUTCOME MEASURES: Survival at 4 years and costs of administration of thrombolysis. RESULTS: Relative to hospital thrombolysis, community thrombolysis gives an additional probability of survival at 4 years of 11% (95% confidence interval 1% to 22%) at an additional cost of 425 pounds per patient. This gives a marginal cost of life saved at 4 years of 3,890 pounds (1,990 pounds to 42,820 pounds). CONCLUSIONS: The cost per life saved by community thrombolysis is modest compared with, for example, the cost of changing the thrombolytic drug used in hospital from streptokinase to alteplase.

Lateral epicondylalgia: a problem for rural workers.

Lateral Epicondylalgia (LE) (tennis elbow) is a problematic condition for workers in labour intensive industries. The economies of many rural communities are founded on industries such as grape growing, meat and fish processing, fruit processing and winemaking. Workers in those industries are at increased risk of developing work-related upper limb mechanical disorders, including LE. This article reviews current understanding of the aetiology and management of this common condition as an aid to rural health professionals managing this presentation. A variety of treatment options exist for the management of LE with the literature divided on which approach is most effective. However, there is evidence that exercise is a key component of a management strategy. In addition to the current practice of prescribing exercises for the wrist extensor muscles, recent research suggests that appropriate activation of the stabilising muscles of the shoulder and cervical spine also needs to be considered by the rural practitioner.

A comparison of smokers' and ex-smokers' health-related quality of life.

BACKGROUND: The aim of the study was to assess the difference in health status between current smokers and ex-smokers of five years or greater standing. METHODS: A group of current smokers and a group of ex-smokers (of five years or greater standing) in Aberdeen, north-east Scotland, were each sent a postal questionnaire containing SF-36, EuroQol, condition-specific and socio-demographic questions. The subjects were 3000 adults (1500 smokers, 1500 ex-smokers) randomly selected from the records of nine general practices. The main outcome measures were the eight scales within the SF-36 health profile, EuroQol tariff scores and assessment of respiratory symptoms. RESULTS: Smoking cessation leads to an improvement in a range of respiratory symptoms and health-related quality of life. However, in some cases other socio-economic characteristics are better indications of quality of life than smoking status. CONCLUSIONS: Smoking cessation leads to a significant improvement in a range of respiratory symptoms. There appear to be significant differences between smokers' and ex-smokers' perceived quality of life. However, these differences are relatively small and in the majority of cases are better explained by variation in age, housing and economic status. When promoting smoking cessation to patients it is possible to highlight expected improvements in respiratory symptoms, impact on global quality of life and longer-term disease effects.

The 1990 GP contract: modelling variation in minor surgery provision.

Logistic regression was used to determine the extent to which general medical practices undertake the maximum amount of minor surgery activity allowed for in the GP contract. Data on activity for 89 practices in the Grampian region of Scotland was available for two consecutive financial years: 1992-93 and 1993-94. Comparison of the regression models developed in each year showed that rural location and practice size were consistently associated with the maximization of minor surgery activity under the terms of 1990 GP Contract. In 1993-94 practices with a greater proportion of deprived patients were also more likely to be 'maximizers'. Quantitative modelling allows the performance of GPs to be assessed and also helps to identify factors which are a barrier to service development. It seems likely that, in Grampian, GPs who were able to exploit fully the provisions of their contract were those whose patients had the greatest capacity to benefit from minor surgery. Currently the GP contract is nationally negotiated, but in the future local negotiated remuneration is likely to become widespread. Modelling will have an important role in the design and monitoring of incentive structures, and help to ensure that service provision equates to local needs.

Economic evaluation of pharmacy services--fact or fiction?

Previous attempts to conduct economic evaluation of pharmacy services are almost exclusively from the US and the UK. Studies from the US concentrate largely on the drug cost savings realised by pharmacists. Few detail the costs of service provision and even fewer give an estimate of service benefits other than decreased drug expenditure. UK evaluation to date focuses on quantifying pharmacists' interventions, but there is no clear indication of the quality or the impact of these. This article proposes a model for economic evaluation and discusses the factors which make evaluation results useful to decision makers. The costs and outcomes, that need to be considered for economic evaluation, are discussed and the example of a pharmacist led anticoagulation clinic is used. The nature of modern health care systems demands that services are effective and, increasingly, cost-effective. If pharmacy as a profession is to develop, decision makers must decide that pharmaceutical care delivered by pharmacists is a cost-effective use of health care resources. Politics, education and cost pressures will mean that decision makers are likely to put more weight on the results of economic evaluation in future. If pharmacists do not start to provide good quality data about the costs and outcomes of pharmacy services then other evaluators will.

Open access gastroscopy: second survey of current practice in the United Kingdom.

In June 1990 a survey of members of the endoscopy section of the British Society of Gastroenterology showed that 47% of respondents were offering some form of open access gastroscopy (OAG). Only 10% offered true (non-censored) OAG. The survey was repeated in June 1994. The overall provision of OAG had risen to 74%, most of whom were offering true OAG. Censored OAG is still widely practised and characterised by referral letters to a consultant in contrast with the use of referral forms (p < 0.001). Referral forms are being increasingly used and are an effective way of capturing important data such as the patients' symptoms (100%), previous treatment (87%), non-steroidal anti-inflammatory drug or aspirin use (78%), suspected diagnosis (74%), and other medical conditions (72%). Forms were used to establish clinical responsibility with the general practitioner in 64% of units. Standardised referral and reporting forms were used by 27% of respondents. A perceived inability to cope with the expected workload was still the most commonly cited reason for not being able to offer OAG. Although 20% of units with a single handed endoscopist were able to offer OAG, this compared with 68% of units with two or more endoscopists (p < 0.001). Only three units indicated that an OAG service had had to be withdrawn, but a further 12 consultants (nine units) were now offering an age restricted service because of excessive workload. Two thirds of the respondents not offering OAG were hoping to do so in the near future. True OAG has increased from 10% to 41% in four years.

ESR study of development of RFM/Un murine myeloid leukaemia.

The blood, spleen and liver of RFM/Un mice were examined by means of electron spin resonance (ESR) throughout the course of myeloid leukaemia induced by i.v. injection of leukaemic spleen cells. Marked changes in the concentration of iron transferrin and caeruloplasmin were observed in the blood 1 day after injection. As the disease progressed, changes occurred in the concentrations of the ascorbyl radical and of paramagnetic metal complexes in both spleen and liver. These changes are compared with those induced in RF/J mice injected with normal and leukaemic spleen cells from RFM/Un mice.

Electron spin resonance study of changes during development of solid Yoshida tumour. I: Ascorbyl radical.

The ascorbyl radical concentration has been observed, by means of electron spin resonance spectroscopy, in the blood and spleen of female Wistar rats carrying a Yoshida tumour. The ascorbyl radical concentration of the tumour tissue itself was studied as the tumour was developing, and as it was regressing after treatment with methylene dimethane sulphonate. Changes in the concentration of this radical may be related to host tumour reactions.

Electron spin resonance study of changes during development of solid yoshida tumour. II. Paramagnetic metal ions.

Electron spin resonance (ESR) spectroscopy was used to examine changes in the concentration of paramagnetic metal ions in Yoshida tumours carried by female Wistar rats. Blood, spleen and lymph nodes from these animals were also examined by ESR. A decrease in the concentration of a paramagnetic species associated with mitochondrial activity, and marked increases in those thought to be associated with inflammatory or immune reactions and cell lysis, were observed in the tumours within one day of implantation. During development of the tumour, and during its regression after treatment with methylene dimethane sulphonate (MDMS), further changes were observed in the concentration of the species. These were dependent on the region of the tumour examined. In blood, development of the tumour produced an increase in ceruloplasmin and a decrease in iron-transferrin. An increase in spleen weight, as the tumour developed, was accompanied by a small decrease in the concentration of species with g-values of 6-0 and 4-3, which was reversed on regression of the treated tumour. The presence of metastases in the regional lymph nodes produced distinguishable changes in the ESR spectra.

Reappraisal of L-canavanine as an anti-tumour agent.

L-canavanine, an analogue of L-arginine, is known to have a toxic effect on pathogens. In experiments performed on a specialised epithelial-like cell system which is conditionally transformable, L-canavanine appeared to exhibit (1) a reversible 'static' effect on exponentially growing cells at optimal concentration, and (2) a selectively toxic effect on proliferating cells. The capacity to recognise 'tumour cells' in a heterogeneous population of cells is of potential interest in cancer chemotherapy.

A dot-blot hybridization procedure for the detection of astrovirus in stool samples.

We have developed a nucleic acid dot-blot hybridization test for the detection of astroviruses in stool samples. The test was not as sensitive as electron microscopy for the detection of low numbers of well preserved astrovirus particles, but was able to identify astroviruses in stools containing particles of indistinct morphology. In total, this procedure identified astroviruses in more samples than did electron microscopy, and the data indicate that the incidence of astroviruses may be substantially underestimated.

The impact of the pharmacist on an elective general surgery pre-admission clinic.

OBJECTIVE: A traditional clinical pharmacy service for surgical patients involves a ward visit that identifies and responds to issues after prescribing has taken place. It was hypothesised that pharmacist involvement in a general surgery pre-admission clinic (PAC) would provide elective patients with significantly better pharmaceutical care than ward visits alone. METHOD: 100 elective general surgery patients were recruited into 2 groups as part of a non-randomised controlled trial. The groups were comparable in terms of age, surgical procedure and use of medicines. The control group received standard ward visits. The intervention group had pharmaceutical assessment in a pre-admission clinic. This assessment incorporated pharmacist-led drug history taking and prescription transcription. OUTCOME MEASURES: Number, classification and clinical significance of pharmaceutical interventions. RESULTS: A pharmacist made 76 interventions in the PAC group and 79 interventions in the ward group. No prescribing errors and omissions were made in the PAC group. The clinical significance of PAC interventions was rated more highly than ward interventions on two scales. Involvement in the PAC increased the pharmacist's workload, but saved time for surgical and nursing staff. Surgical and nursing staff identified writing discharge prescriptions as the most valuable service provided by the PAC pharmacist. CONCLUSION: By ensuring safe prescribing in the PAC group, the pharmacist was able to become more involved in clinical issues. Pharmacist involvement in PACs presents a useful opportunity for expansion of pharmacy services. However, extra resources would be needed in order to provide these services fully.