An online intervention for carers to manage behavioral symptoms in motor neuron disease (MiNDToolkit): a randomized parallel multi-center feasibility trial.

BACKGROUND: Evidence on management of behavioral symptoms in motor neuron disease (MND) is lacking. The MiNDToolkit, an online psychoeducational platform, supports carers dealing with behavioral symptoms (BehSymp). The study objectives were to ascertain recruitment and retention rates, carer and healthcare professional (HCP) use of the platform, and completion of online assessments, to inform a full-scale trial. Design: Randomized, parallel, multi-center, feasibility trial. SETTING: England and Wales, across diverse MND services; recruitment from July/21 to November/22; last participant follow-up in March/23. PARTICIPANTS: Carers of people with motor neuron disease (PwMND) with BehSymp, recruited through MND services. After confirming eligibility, participants completed screening and baseline assessments online via the MiNDToolkit platform and were randomized centrally in a 1:1 ratio to MiNDToolkit or control. INTERVENTION: MiNDToolkit offered tailored modules to carers for the 3-month study period. Carers in the intervention group could receive additional support from MiNDToolkit trained HCPs. The control group was offered access to the intervention at the end of the study. Data were collected on platform usage and psychosocial variables. MAIN OUTCOMES: One hundred and fifty-one carers from 11 sites were invited to join the study (letter, face-to-face); 30 were screened; 29 were randomized. Fifteen people were allocated to the control arm; 14 to intervention. Carers were mostly female; median age for was 62.5 (IQR: 58, 68; intervention) and 57 (IQR: 56, 70; controls). Study retention was high (24/29 = 82.76%); carers engaged with the platform on average 14 times (median (IQR):14.0 (10.0, 18.5)) during the study period. CONCLUSION: The MiNDToolkit study was feasible and well accepted by carers and trained HCPs. A definitive trial is warranted.

Evaluating Palin Stammering Therapy for School Children (Palin STSC 8-14): protocol for a feasibility randomised controlled trial comparing Palin STSC(8-14) with usual treatment.

BACKGROUND: Having a stammer can have a significant effect on a child's social, emotional and educational development. With approximately 66,000 children in the UK having a stammer, there is a need to establish an adequate evidence base to inform clinical practice. We describe a feasibility trial to explore the effectiveness of a new therapy programme for children aged 8-14: Palin Stammering Therapy for School Children (Palin STSC(8-14)). Preliminary data from the Michael Palin Centre, where the programme was developed, indicate that Palin STSC(8-14) is effective in reducing stammering frequency and impact for children, with beneficial effects for parents too. We will investigate the feasibility of the methods required for a definitive randomised controlled trial to investigate the application of this therapy by NHS speech and language therapists (SLTs), compared with 'treatment as usual' (TAU), beyond the specialist context in which it was developed. METHODS: This is a two-arm feasibility cluster-randomised controlled trial of Palin STSC(8-14) with TAU control arm, and randomisation at the level of the SLT. Quantitative and qualitative data will be collected to examine the following: the recruitment and retention of therapists and families, the acceptability of the research processes and the therapeutic intervention and the appropriateness of the therapy outcome measures. Assessments will be completed by children and parents at baseline and 6 months later, including measures of stammering severity; the impact of child's stammering on both children and parents; child temperament, behaviour and peer relations, anxiety; quality of life; and economic outcomes. There will also be a qualitative process evaluation, including interviews with parents, children, SLTs and SLT managers to explore the acceptability of both the research and therapy methods. Treatment fidelity will be examined through analysis of therapy session records and recordings. DISCUSSION: The findings of this feasibility trial will inform the decision as to whether to progress to a full-scale randomised controlled trial to explore the effectiveness of Palin STSC(8-14) when compared to Treatment as Usual in NHS SLT services. There is a strong need for an evidence-based intervention for school age children who stammer. TRIAL REGISTRATION: ISRCTN. ISRCTN17058884 . Registered on 18 December 2019.

Long-term cost-effectiveness of screening for fracture risk in a UK primary care setting: the SCOOP study.

Community-based screening and treatment of women aged 70-85 years at high fracture risk reduced fractures; moreover, the screening programme was cost-saving. The results support a case for a screening programme of fracture risk in older women in the UK. INTRODUCTION: The SCOOP (screening for prevention of fractures in older women) randomized controlled trial investigated whether community-based screening could reduce fractures in women aged 70-85 years. The objective of this study was to estimate the long-term cost-effectiveness of screening for fracture risk in a UK primary care setting compared with usual management, based on the SCOOP study. METHODS: A health economic Markov model was used to predict the life-time consequences in terms of costs and quality of life of the screening programme compared with the control arm. The model was populated with costs related to drugs, administration and screening intervention derived from the SCOOP study. Fracture risk reduction in the screening arm compared with the usual management arm was derived from SCOOP. Modelled fracture risk corresponded to the risk observed in SCOOP. RESULTS: Screening of 1000 patients saved 9 hip fractures and 20 non-hip fractures over the remaining lifetime (mean 14 years) compared with usual management. In total, the screening arm saved costs (£286) and gained 0.015 QALYs/patient in comparison with usual management arm. CONCLUSIONS: This analysis suggests that a screening programme of fracture risk in older women in the UK would gain quality of life and life years, and reduce fracture costs to more than offset the cost of running the programme.

Screening for high hip fracture risk does not impact on falls risk: a post hoc analysis from the SCOOP study.

A reduction in hip fracture incidence following population screening might reflect the effectiveness of anti-osteoporosis therapy, behaviour change to reduce falls, or both. This post hoc analysis demonstrates that identifying high hip fracture risk by FRAX was not associated with any alteration in falls risk. INTRODUCTION: To investigate whether effectiveness of an osteoporosis screening programme to reduce hip fractures was mediated by modification of falls risk in the screening arm. METHODS: The SCOOP study recruited 12,483 women aged 70-85 years, individually randomised to a control (n = 6250) or screening (n = 6233) arm; in the latter, osteoporosis treatment was recommended to women at high risk of hip fracture, while the control arm received usual care. Falls were captured by self-reported questionnaire. We determined the influence of baseline risk factors on future falls, and then examined for differences in falls risk between the randomisation groups, particularly in those at high fracture risk. RESULTS: Women sustaining one or more falls were slightly older at baseline than those remaining falls free during follow-up (mean difference 0.70 years, 95%CI 0.55-0.85, p < 0.001). A higher FRAX 10-year probability of hip fracture was associated with increased likelihood of falling, with fall risk increasing by 1-2% for every 1% increase in hip fracture probability. However, falls risk factors were well balanced between the study arms and, importantly, there was no evidence of a difference in falls occurrence. In particular, there was no evidence of interaction (p = 0.18) between baseline FRAX hip fracture probabilities and falls risk in the two arms, consistent with no impact of screening on falls in women informed to be at high risk of hip fracture. CONCLUSION: Effectiveness of screening for high FRAX hip fracture probability to reduce hip fracture risk was not mediated by a reduction in falls.

Systematic screening using FRAX® leads to increased use of, and adherence to, anti-osteoporosis medications: an analysis of the UK SCOOP trial.

In the large community-based SCOOP trial, systematic fracture risk screening using FRAX® led to greater use of AOM and greater adherence, in women at high fracture risk, compared with usual care. INTRODUCTION: In the SCreening of Older wOmen for Prevention of fracture (SCOOP) trial, we investigated the effect of the screening intervention on subsequent long-term self-reported adherence to anti-osteoporosis medications (AOM). METHODS: SCOOP was a primary care-based UK multicentre trial of screening for fracture risk. A total of 12,483 women (70-85 years) were randomised to either usual NHS care, or assessment using the FRAX® tool ± dual-energy X-ray absorptiometry (DXA), with medication recommended for those found to be at high risk of hip fracture. Self-reported AOM use was obtained by postal questionnaires at 6, 12, 24, 36, 48 and 60 months. Analysis was limited to those who initiated AOM during follow-up. Logistic regression was used to explore baseline determinants of adherence (good ≥ 80%; poor < 80%). RESULTS: The mean (SD) age of participants was 75.6 (4.2) years, with 6233 randomised to screening and 6250 to the control group. Of those participants identified at high fracture risk in the screening group, 38.2% of those on treatment at 6 months were still treated at 60 months, whereas the corresponding figure for the control group was 21.6%. Older age was associated with poorer adherence (OR per year increase in age 0.96 [95% CI 0.93, 0.99], p = 0.01), whereas history of parental hip fracture was associated with greater rate adherence (OR 1.67 [95% CI 1.23, 2.26], p < 0.01). CONCLUSIONS: Systematic fracture risk screening using FRAX® leads to greater use of AOM and greater adherence, in women at high fracture risk, compared with usual care.

Does sensory relearning improve tactile function after carpal tunnel decompression? A pragmatic, assessor-blinded, randomized clinical trial.

Despite surgery for carpal tunnel syndrome being effective in 80%-90% of cases, chronic numbness and hand disability can occur. The aim of this study was to investigate whether sensory relearning improves tactile discrimination and hand function after decompression. In a multi-centre, pragmatic, randomized, controlled trial, 104 patients were randomized to a sensory relearning ( n = 52) or control ( n = 52) group. A total of 93 patients completed a 12-week follow-up. Primary outcome was the shape-texture identification test at 6 weeks. Secondary outcomes were touch threshold, touch localization, dexterity and self-reported hand function. No significant group differences were seen for the primary outcome (Shape-Texture Identification) at 6 weeks or 12 weeks. Similarly, no significant group differences were observed on secondary outcomes, with the exception of self-reported hand function. A secondary complier-averaged-causal-effects analysis showed no statistically significant treatment effect on the primary outcome. Sensory relearning for tactile sensory and functional deficits after carpal tunnel decompression is not effective. LEVEL OF EVIDENCE: II.

Supervised pharmacy student-led medication review in primary care for patients with type 2 diabetes: a randomised controlled pilot study.

OBJECTIVE: To pilot and feasibility-test supervised final year undergraduate pharmacy student-led medication reviews for patients with diabetes to enable definitive trial design. METHOD: Third year pharmacy students were recruited from one UK School of Pharmacy and trained to review patient's medical records and provide face-to-face consultations under supervision while situated within the patient's medical practice. Patients with type 2 diabetes were recruited by postal invitation letter from their medical practice and randomised via automated system to intervention or usual care. Diabetes-related clinical data, quality of life, patient reported beliefs, adherence and satisfaction with medicines information were collected with validated tools at baseline and 6 months postintervention. The process for collecting resource utilisation data was tested. Stakeholder meetings were held before and after intervention to develop study design and learn from its implementation. Recruitment and attrition rates were determined plus the quality of the outcome data. Power calculations for a definitive trial were performed on the different outcome measures to identify the most appropriate primary outcome measure. RESULTS: 792 patients were identified as eligible from five medical practices. 133 (16.8%) were recruited and randomised to control (n=66) or usual care (n=67). 32 students provided the complete intervention to 58 patients. Initial data analysis showed potential for impact in the right direction for some outcomes measured including glycated haemoglobin, quality of life and patient satisfaction with information about medicines. The intervention was found to be feasible and acceptable to patients. The pilot and feasibility study enabled the design of a future full randomised controlled trial. CONCLUSIONS: Student and patient recruitment are possible. The intervention was well received and demonstrated some potential benefits. While the intervention was relatively inexpensive and provided an experiential learning opportunity for pharmacy students, its cost-effectiveness remains to be determined. TRIAL REGISTRATION NUMBER: ISRCTN26445805; Results.

A systematic review of the pharmacological management of orthostatic hypotension.

OBJECTIVES: The 'short' and 'long-term' benefits of pharmacological interventions to treat orthostatic hypotension (OH) remain unclear. The aim was to systematically examine the published literature on the effectiveness of different drug regimens for the treatment of OH. DESIGN: Systematic review. SETTING: MEDLINE (1950-Week 7, 2011), EMBASE (1980-Week 7, 2011), CINAHL (1981-Week 7, 2011) databases and hand-searching of bibliographies were used to identify suitable papers. PARTICIPANTS: Studies selected were those, which investigated drug treatment of OH in a single- or double-blind randomised controlled trial (RCT) in humans over 18 years of age. MEASUREMENTS: Data were extracted from suitable full-text articles by three investigators independently. RESULTS: The 13 trials met the criteria for systematic review amongst which was considerable variation in the size of postural blood pressure (BP) change with active treatment. However, there was evidence that commonly used drugs midodrine or fludrocortisone therapy did increase standing or head-up-tilt (HUT) systolic blood pressure in certain patient groups. CONCLUSION: The evidence that pharmacological therapy is of benefit for the treatment of OH is limited by the lack of good quality clinical trial evidence. Further well-designed RCTs of pharmacological treatment of OH investigating the impact on postural symptoms as well as actual BP changes are needed.

A pragmatic randomised controlled trial of the effectiveness and cost-effectiveness of screening older women for the prevention of fractures: rationale, design and methods for the SCOOP study.

SCOOP is a UK seven-centre, pragmatic, randomised controlled trial with 5-year follow-up, including 11,580 women aged 70 to 85 years, to assess the effectiveness and cost-effectiveness of a community-based screening programme to reduce fractures. It utilises the FRAX algorithm and DXA to assess the 10-year probability of fracture. Introduction Osteoporotic, or low-trauma, fractures present a considerable burden to the National Health Service and have major adverse effects on quality of life, disability and mortality for the individual. Methods Given the availability of efficacious treatments and a risk assessment tool based upon clinical risk factors and bone mineral density, a case exists to undertake a community-based controlled evaluation of screening for subjects at high risk of fracture, under the hypothesis that such a screening programme would reduce fractures in this population. Results This study is a UK seven-centre, unblinded, pragmatic, randomised controlled trial with a 5-year follow-up period. A total of 11,580 women, aged 70 to 85 years and not on prescribed bone protective therapy will be consented to the trial by post via primary care providing 90% power to detect an 18% decrease in fractures. Conclusions Participants will be randomised to either a screening arm or control. Those undergoing screening will have a 10-year fracture probability computed from baseline risk factors together with bone mineral density measured by DXA in selected subjects. Individuals above an age-dependent threshold of fracture probability will be recommended for treatment for the duration of the trial. Subjects in the control arm will receive 'usual care'. Participants will be followed up 6 months after randomisation and annually by postal questionnaires with independent checking of hospital and primary care records. The primary outcome will be the proportion of individuals sustaining fractures in each group. An economic analysis will be carried out to assess cost-effectiveness of screening. A qualitative evaluation will be conducted to examine the acceptability of the process to participants.

Secondary signs on static stress MRI in anterior cruciate ligament rupture.

The MRI diagnosis of ACL rupture based on primary signs has variable rates of diagnostic accuracy. These signs observed on direct visualisation of the ACL include discontinuity of fibres, abnormal ligament contour and increased intrasubstance signal intensity. Secondary radiological signs of ACL rupture are increasingly being used. These indirect ancillary signs include PCL angle, translocation of the tibia relative to the femur and displacement of the posterior horns of the menisci. The aim of this study was to investigate if the application of static stress force to the knee will accentuate the secondary signs of ACL rupture on MRI. One hundred and forty-eight subjects (50 subjects with arthroscopically confirmed ACL rupture, 48 subjects with arthroscopically confirmed intact ACL and 50 subjects with clinically confirmed normal knees) underwent MRI of their knee with the application of specially designed fibreglass leg splints which exert a translational force on the knee joint. Five secondary radiological signs were evaluated and all were found to be significantly accentuated following the application of the splints (p<0.001). The MRI diagnosis of ACL rupture demonstrated a sensitivity of 95.9%, specificity of 91.7% and accuracy of 93.8%. The static stress technique improved the accuracy of diagnosing ACL ruptures on MRI and illustrated the abnormal tibiofemoral kinematics.

Proprioception following partial meniscectomy in stable knees.

PURPOSE: to investigate the proprioceptive function of patients with isolated meniscal tears of the knee before and after arthroscopic partial meniscectomy. METHODS: one hundred subjects (50 patients who underwent a knee arthroscopy and 50 normal controls) were evaluated using single-leg dynamic postural stabilometry. All participants were assessed clinically and radiologically. Knee outcome scores were obtained for all subjects. RESULTS: of the 50 patients arthroscoped, 34 were found to have meniscal tears. Twenty-nine of these patients were reassessed 3 months post-operatively. There was a significant proprioceptive deficit in subjects with meniscal tears when compared to their normal contra-lateral knee (P < 0.001) and the control group (P < 0.001). Partial meniscectomy resulted in a significant improvement in knee outcome scores but not proprioception measurements (n.s.). CONCLUSION: patients with isolated meniscal tears were found to have a significant proprioceptive deficit which persisted following arthroscopic partial meniscectomy despite an otherwise successful clinical outcome.

A randomised controlled equivalence trial to determine the effectiveness and cost-utility of manual chest physiotherapy techniques in the management of exacerbations of chronic obstructive pulmonary disease (MATREX).

OBJECTIVES: To estimate the effect, if any, of manual chest physiotherapy (MCP) administered to patients hospitalised with chronic obstructive pulmonary disease (COPD) exacerbation on both disease-specific and generic health-related quality of life. To compare the health service costs for those receiving and not receiving MCP. DESIGN: A pragmatic, randomised controlled trial powered for equivalence. It was not possible to blind participants, clinicians or research staff to study arm allocation during the intervention. SETTING: Four UK hospitals in Norwich, Great Yarmouth, King's Lynn and Liverpool. PARTICIPANTS: 526 participants aged 34-91 years were recruited between November 2005 and April 2008; of these, 372 provided evaluable data for the primary outcome. All persons hospitalised with COPD exacerbation and evidence of sputum production on examination were eligible for the trial providing there were no contraindications to performing MCP. INTERVENTIONS: Participants were allocated to either MCP or no MCP on an intention-to-treat (ITT) basis. However, active cycle of breathing techniques (ACBT) was used in both arms. Participants allocated to the intervention were guided to perform ACBT while the physiotherapist delivered MCP. Participants allocated to the control arm received instruction on ACBT only. MAIN OUTCOME MEASURES: The primary outcome was COPD-specific quality of life, measured using the St George's Respiratory Questionnaire (SGRQ) at 6 months post randomisation. The European Quality of Life-5 Dimensions (EQ-5D) questionnaire was used to calculate the quality-adjusted life-year (QALY) gain associated with MCP compared with no MCP. Secondary physiological outcome measures were also used. RESULTS: Of the 526 participants, 261 were allocated to MCP and 264 to control, with 186 participants evaluable in each arm. ITT analyses indicated no significant difference at 6 months post randomisation in total SGRQ score [adjusted effect size (no MCP - MCP) 0.03 (95% confidence interval, CI -0.14 to 0.19)], SGRQ symptom score [adjusted effect size 0.04 (95% CI -0.15 to 0.23)], SGRQ activity score [adjusted effect size -0.02 (95% CI -0.20 to 0.16)] or SGRQ impact score [adjusted effect size 0.02 (95% CI -0.15 to 0.18)]. The imputed ITT and per-protocol results were similar. No significant differences were observed in any of the outcome measures or subgroup analyses. Compared with no MCP, employing MCP was associated with a slight loss in quality of life (0.001 QALY loss) but lower health service costs (cost saving of 410.79 pounds). Based on these estimates, at a cost-effectiveness threshold of lambda = 20,000 pounds per QALY, MCP would constitute a cost-effective use of resources (net benefit = 376.14 pounds). There was, however, a high level of uncertainty associated with these results and it is possible that the lower health service costs could have been due to other factors. CONCLUSIONS: In terms of longer-term quality of life the use of MCP did not appear to affect outcome. However, this does not mean that MCP is of no therapeutic value to patients with COPD in specific circumstances. Although the cost-effectiveness analysis suggested that its use was cost-effective, much uncertainty was associated with this finding and it would be difficult to justify providing MCP therapy on the basis of cost-effectiveness alone. Future research should include evaluation of MCP for patients with COPD producing high volumes of sputum, and an evaluation of the effectiveness of ACBT in COPD exacerbation. TRIAL REGISTRATION: Current Controlled Trials ISRCTN13825248.

The effect of travoprost on daytime intraocular pressure in normal tension glaucoma: a randomised controlled trial.

BACKGROUND/AIMS: To determine the medium-term effect of travoprost on the daytime intraocular pressure (IOP) of patients with normal tension glaucoma (NTG) METHODS: Newly diagnosed NTG patients underwent baseline, daytime, hourly IOP phasing. Patients were randomised to either treatment or no treatment (control). Treatment comprised once daily topical travoprost 0.004%. After 6 months, the participants underwent their second IOP phasing. RESULTS: Data from 88 participants were analysed-54 were randomised to treatment and 34 to the control group. The mean duration of treatment was 6 months. The average, maximum and minimum diurnal IOPs for treated patients were statistically significantly lower than for control patients at follow-up (p<0.001). When compared with baseline IOP, the travoprost treated group demonstrated a decrease of 16.1%, 13.5% and 16.7% in the average IOP, maximum IOP, and minimum IOP respectively. Of those treated, about one-third achieved a decrease in average IOP of at least 20%; only about one-tenth achieved a reduction of at least 30%. CONCLUSION: Travoprost monotherapy had a sustained hypotensive effect in NTG and achieved a reasonable or good response (>20% reduction in average IOP) in 32.9% of treated eyes. However, in the majority of eyes with NTG, travoprost monotherapy appeared unable to produce the desirable 30% reduction in average IOP.

Does befriending by trained lay workers improve psychological well-being and quality of life for carers of people with dementia, and at what cost? A randomised controlled trial.

OBJECTIVES: To determine whether a social support intervention (access to an employed befriending facilitator in addition to usual care) is effective compared with usual care alone. Also to document direct and indirect costs, and establish incremental cost-effectiveness. DESIGN: The Befriending and Costs of Caring (BECCA) trial was a cost-effectiveness randomised controlled trial. Data on well-being and resource use were collected through interviews with participants at baseline and at 6, 15 and 24 months. SETTING: This research was carried out in the English counties of Norfolk and Suffolk, and the London Borough of Havering. It was a community-based study. PARTICIPANTS: Participants were family carers who were cohabiting with, or providing at least 20 hours' care per week for, a community-dwelling relative with a primary progressive dementia. INTERVENTIONS: The intervention was 'access to a befriender facilitator' (BF). BFs, based with charitable/voluntary-sector organisations, were responsible for local befriending schemes, including recruitment, screening, training and ongoing support of befriending volunteers, and for matching carers with befrienders. The role of befrienders was to provide emotional support for carers. The target duration for befriending relationships was 6 months or more. MAIN OUTCOME MEASURES: Depression was measured by the Hospital Anxiety and Depression Scale (HADS) at 15 months postrandomisation. The health-related quality of life scale EQ-5D (EuroQol 5 Dimensions) was used to derive utilities for the calculation of quality-adjusted life-years (QALYs). RESULTS: A total of 236 carers were randomised into the trial (116 intervention; 120 control). At final follow-up, 190 carers (93 intervention; 97 control) were still involved in the trial (19% attrition). There was no evidence of effectiveness or cost-effectiveness from the primary analyses on the intention-to-treat population. The mean incremental cost per incremental QALY gained was in excess of 100,000 pounds, with only a 42.2% probability of being below 30,000 pounds per QALY gained. Where care-recipient QALYs were included, mean incremental cost per incremental QALY gained was 26,848 pounds, with a 51.4% probability of being below 30,000 pounds per QALY gained. Only 60 carers (52%) took up the offer of being matched with a trained lay befriender, and of these only 37 (32%) were befriended for 6 months or more. A subgroup analysis of controls versus those befriended for 6 months or more found a reduction in HADS-depression scores that approached statistical significance (95% CI -0.09 to 2.84). CONCLUSIONS: 'Access to a befriender facilitator' is neither an effective nor a cost-effective intervention in the support of carers of people with dementia, although there is a suggestion of cost-effectiveness for the care dyad (carer and care recipient). In common with many services for carers of people with dementia, uptake of befriending services was not high. However, the small number of carers who engaged with befrienders for 6 months or more reported a reduction in scores on HADS depression that approached statistical significance compared with controls (95% CI -0.09 to 2.84). While providing only weak evidence of any beneficial effect, further research into befriending interventions for carers is warranted.

Contamination in trials of educational interventions.

OBJECTIVES: To consider the effects of contamination on the magnitude and statistical significance (or precision) of the estimated effect of an educational intervention, to investigate the mechanisms of contamination, and to consider how contamination can be avoided. DATA SOURCES: Major electronic databases were searched up to May 2005. METHODS: An exploratory literature search was conducted. The results of trials included in previous relevant systematic reviews were then analysed to see whether studies that avoided contamination resulted in larger effect estimates than those that did not. Experts' opinions were elicited about factors more or less likely to lead to contamination. We simulated contamination processes to compare contamination biases between cluster and individually randomised trials. Statistical adjustment was made for contamination using Complier Average Causal Effect analytic methods, using published and simulated data. The bias and power of cluster and individually randomised trials were compared, as were Complier Average Causal Effect, intention-to-treat and per protocol methods of analysis. RESULTS: Few relevant studies quantified contamination. Experts largely agreed on where contamination was more or less likely. Simulation of contamination processes showed that, with various combinations of timing, intensity and baseline dependence of contamination, cluster randomised trials might produce biases greater than or similar to those of individually randomised trials. Complier Average Causal Effect analyses produced results that were less biased than intention-to-treat or per protocol analyses. They also showed that individually randomised trials would in most situations be more powerful than cluster randomised trials despite contamination. CONCLUSIONS: The probability, nature and process of contamination should be considered when designing and analysing controlled trials of educational interventions in health. Cluster randomisation may or may not be appropriate and should not be uncritically assumed always to be a solution. Complier Average Causal Effect models are an appropriate way to adjust for contamination if it can be measured. When conducting such trials in future, it is a priority to report the extent, nature and effects of contamination.

A systematic review of the clinical, public health and cost-effectiveness of rapid diagnostic tests for the detection and identification of bacterial intestinal pathogens in faeces and food.

OBJECTIVES: To determine the diagnostic accuracy of tests for the rapid diagnosis of bacterial food poisoning in clinical and public health practice and to estimate the cost-effectiveness of these assays in a hypothetical population in order to inform policy on the use of these tests. DATA SOURCES: Studies evaluating diagnostic accuracy of rapid tests were retrieved using electronic databases and handsearching reference lists and key journals. Hospital laboratories and test manufacturers were contacted for cost data, and clinicians involved in the care of patients with food poisoning were invited to discuss the conclusions of this review using the nominal group technique. REVIEW METHODS: A systematic review of the current medical literature on assays used for the rapid diagnosis of bacterial food poisoning was carried out. Specific organisms under review were Salmonella, Campylobacter, Escherichia coli O157, Staphylococcus aureus, Clostridium perfringens and Bacillus cereus. Data extraction was undertaken using standardised data extraction forms. Where a sufficient number of studies evaluating comparable tests were identified, meta-analysis was performed. A decision analytic model was developed, using effectiveness data from the review and cost data from hospitals and manufacturers, which contributed to an assessment of the cost-effectiveness of rapid tests in a hypothetical UK population. Finally, diagnostic accuracy and cost-effectiveness results were presented to a focus group of GPs, microbiologists and consultants in communicable disease control, to assess professional opinion on the use of rapid tests in the diagnosis of food poisoning. RESULTS: Good test performance levels were observed with rapid test methods, especially for polymerase chain reaction (PCR) assays. The estimated levels of diagnostic accuracy using the area under the curve of the summary receiver operating characteristic curve was very high. Indeed, although traditional culture is the natural reference test to use for comparative statistical analysis, on many occasions the rapid test outperforms culture, detecting additional 'truly' positive cases of food-borne illness. The significance of these additional positives requires further investigation. Economic modelling suggests that adoption of rapid tests in combination with routine culture is unlikely to be cost-effective, however, as the cost of rapid technologies decreases; total replacement with rapid technologies may be feasible. CONCLUSIONS: Despite the relatively poor quality of reporting of studies evaluating rapid detection methods, the reviewed evidence shows that PCR for Campylobacter, Salmonella and E. coli O157 is potentially very successful in identifying pathogens, possibly detecting more than the number currently reported using culture. Less is known about the benefits of testing for B. cereus, C. perfringens and S. aureus. Further investigation is needed on how clinical outcomes may be altered if test results are available more quickly and at a greater precision than in the current practice of bacterial culture.

Three-year single institution audit on transfusion requirements in oncology patients.

AIMS: To assess recent developments in the use of transfusions. MATERIALS AND METHODS: Data from hospital-based sources were condensed in a single spread sheet covering 1611 transfusions of a total of 881 patients together with data on 25,264 treatment sessions in 6137 patients within a time period between 1 August 2001 and 31 July 2004. RESULTS: Our audit showed an increase in transfusions of 25% in 3 years. This was accompanied by an increased threshold for transfusions, as shown by a significant rise in mean haemoglobin trigger levels from 8.53 to 8.86 g/dl (P<0.001) as well as an increase in treatment sessions and patient numbers - especially for chemotherapy or combinations of chemotherapy and radiotherapy. The highest transfusion rates and also the greatest increments occurred in patients with carcinoma of the ovary, lung and pancreas. Within these groups, treatment regimens as well as treatment lines were additional predictive factors. CONCLUSIONS: This audit gives a detailed view on rising trends in transfusion requirements and, in light of anticipated restrictions on resources, it identifies high-risk areas, where the use of alternatives, such as erythropoietin, could be considered.

The reliability and validity of the locognosia test after injuries to peripheral nerves in the hand.

Locognosia, the ability to localise touch, is one aspect of tactile spatial discrimination which relies on the integrity of peripheral end-organs as well as the somatosensory representation of the surface of the body in the brain. The test presented here is a standardised assessment which uses a protocol for testing locognosia in the zones of the hand supplied by the median and/or ulnar nerves. The test-retest reliability and discriminant validity were investigated in 39 patients with injuries to the median or ulnar nerve. Intraclass correlation coefficients were used to calculate the test-retest reliability. Discriminant validity was assessed by comparing the injured with the unaffected hand. Excellent test-retest reliability was demonstrated for the injuries to the median (intraclass correlation coefficient 0.924, 95% confidence interval 0.848 to 1.00) and the ulnar nerves (intraclass correlation coefficient 0.859, 95% confidence interval 0.693 to 1.00). The magnitude of the difference in scores between affected and unaffected hands showed good discriminant validity. For injuries to the median nerve the mean difference was 11.1 points (1 to 33; SD 7.4), which was statistically significant (p < 0.0001, paired t-test) and for those of the ulnar nerve it was 4.75 points (1 to 13.5; SD 3.16), which was also statistically significant (paired t-test, p < 0.0001). The locognosia test has excellent test-retest reliability, is a valid test of tactile spatial discrimination and should be included in the evaluation of outcome after injury to peripheral nerves.