No statistically significant kinematic difference found between a cruciate-retaining and posterior-stabilised Triathlon knee arthroplasty: a laboratory study involving eight cadavers examining soft-tissue laxity.

The aim of this study was to compare the maximum laxity conferred by the cruciate-retaining (CR) and posterior-stabilised (PS) Triathlon single-radius total knee arthroplasty (TKA) for anterior drawer, varus-valgus opening and rotation in eight cadaver knees through a defined arc of flexion (0º to 110º). The null hypothesis was that the limits of laxity of CR- and PS-TKAs are not significantly different. The investigation was undertaken in eight loaded cadaver knees undergoing subjective stress testing using a measurement rig. Firstly the native knee was tested prior to preparation for CR-TKA and subsequently for PS-TKA implantation. Surgical navigation was used to track maximal displacements/rotations at 0º, 30º, 60º, 90º and 110° of flexion. Mixed-effects modelling was used to define the behaviour of the TKAs. The laxity measured for the CR- and PS-TKAs revealed no statistically significant differences over the studied flexion arc for the two versions of TKA. Compared with the native knee both TKAs exhibited slightly increased anterior drawer and decreased varus-valgus and internal-external roational laxities. We believe further study is required to define the clinical states for which the additional constraint offered by a PS-TKA implant may be beneficial.

Spatial variation in the risk of hospitalization with childhood pneumonia and empyema in the North of England.

The aim of this study was to investigate spatial variation in risk of hospitalization in childhood pneumonia and empyema in the North of England and associated risk factors. Data on childhood (0-14 years) hospital admissions with a diagnosis pneumonia or empyema were linked to postcode districts. Bayesian conditional autoregressive models were used to evaluate spatial variation and the relevance of specific spatial covariates in an area-based study using postcode as the areal unit. There was a sixfold variation in the risk of hospitalization due to pneumonia across the study region. Variation in risk was associated with material deprivation, Child Well-being Index (CWI) health domain score, number of children requiring local authority support, and distance to hospital. No significant spatial variation in risk for empyema was found.

Impact of the 7-valent pneumococcal conjugate vaccine on the incidence of childhood pneumonia.

In September 2006, the 7-valent pneumococcal conjugate vaccine (PCV7) was added to the UK immunization programme. We aimed to evaluate the impact of PCV7 on the incidence of all-cause community-acquired pneumonia (CAP) in children. A prospective survey was undertaken in 2008-2009 at 11 hospitals in North East England of children aged 0-16 years with radiologically confirmed pneumonia. Data were compared to those from a similar survey undertaken in the same hospitals in 2001-2002. A total of 542 children were enrolled, of which 74% were aged <5 years. PCV7 uptake was 90∙7%. The incidence of pneumonia was 11∙8/10,000 [95% confidence interval (CI) 10∙9-12∙9], and the hospitalization rate was 9∙9/10,000 (95% CI 9∙0-10∙9). Compared to 2001, there was a 19% (95% CI 8-29) reduction in the rate of CAP in those aged <5 years, and in those <2 years a 33∙1% (95% CI 20-45) reduction in the incidence of CAP and 38∙1% (95% CI 24-50) reduction in hospitalization rates. However, for those unvaccinated aged ≥5 years, there was no difference in the incidence of CAP and hospitalization rate between both surveys. Since 2001, the overall reduction in incidence was 17∙7% (95% CI 8-26) and for hospitalization 18∙5% (95% CI 8-28). For the <5 years age group there was a lower incidence of CAP in PCV7-vaccinated children (25∙2/10,000, 95% CI 22∙6-28∙2) than in those that were not vaccinated (37∙4/10,000, 95% CI 29∙2-47∙1). In conclusion, PCV7 has reduced both incidence and rate of hospitalization of pneumonia in children, particularly in the <2 years age group.

Systematic review and economic modelling of the relative clinical benefit and cost-effectiveness of laparoscopic surgery and robotic surgery for removal of the prostate in men with localised prostate cancer.

BACKGROUND: Complete surgical removal of the prostate, radical prostatectomy, is the most frequently used treatment option for men with localised prostate cancer. The use of laparoscopic (keyhole) and robot-assisted surgery has improved operative safety but the comparative effectiveness and cost-effectiveness of these options remains uncertain. OBJECTIVE: This study aimed to determine the relative clinical effectiveness and cost-effectiveness of robotic radical prostatectomy compared with laparoscopic radical prostatectomy in the treatment of localised prostate cancer within the UK NHS. DATA SOURCES: MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, BIOSIS, Science Citation Index and Cochrane Central Register of Controlled Trials were searched from January 1995 until October 2010 for primary studies. Conference abstracts from meetings of the European, American and British Urological Associations were also searched. Costs were obtained from NHS sources and the manufacturer of the robotic system. Economic model parameters and distributions not obtained in the systematic review were derived from other literature sources and an advisory expert panel. REVIEW METHODS: Evidence was considered from randomised controlled trials (RCTs) and non-randomised comparative studies of men with clinically localised prostate cancer (cT1 or cT2); outcome measures included adverse events, cancer related, functional, patient driven and descriptors of care. Two reviewers abstracted data and assessed the risk of bias of the included studies. For meta-analyses, a Bayesian indirect mixed-treatment comparison was used. Cost-effectiveness was assessed using a discrete-event simulation model. RESULTS: The searches identified 2722 potentially relevant titles and abstracts, from which 914 reports were selected for full-text eligibility screening. Of these, data were included from 19,064 patients across one RCT and 57 non-randomised comparative studies, with very few studies considered at low risk of bias. The results of this study, although associated with some uncertainty, demonstrated that the outcomes were generally better for robotic than for laparoscopic surgery for major adverse events such as blood transfusion and organ injury rates and for rate of failure to remove the cancer (positive margin) (odds ratio 0.69; 95% credible interval 0.51 to 0.96; probability outcome favours robotic prostatectomy = 0.987). The predicted probability of a positive margin was 17.6% following robotic prostatectomy compared with 23.6% for laparoscopic prostatectomy. Restriction of the meta-analysis to studies at low risk of bias did not change the direction of effect but did decrease the precision of the effect size. There was no evidence of differences in cancer-related, patient-driven or dysfunction outcomes. The results of the economic evaluation suggested that when the difference in positive margins is equivalent to the estimates in the meta-analysis of all included studies, robotic radical prostatectomy was on average associated with an incremental cost per quality-adjusted life-year that is less than threshold values typically adopted by the NHS (£30,000) and becomes further reduced when the surgical capacity is high. LIMITATIONS: The main limitations were the quantity and quality of the data available on cancer-related outcomes and dysfunction. CONCLUSIONS: This study demonstrated that robotic prostatectomy had lower perioperative morbidity and a reduced risk of a positive surgical margin compared with laparoscopic prostatectomy although there was considerable uncertainty. Robotic prostatectomy will always be more costly to the NHS because of the fixed capital and maintenance charges for the robotic system. Our modelling showed that this excess cost can be reduced if capital costs of equipment are minimised and by maintaining a high case volume for each robotic system of at least 100-150 procedures per year. This finding was primarily driven by a difference in positive margin rate. There is a need for further research to establish how positive margin rates impact on long-term outcomes. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Farm-scale risk factors for bovine tuberculosis incidence in cattle herds during the Randomized Badger Culling Trial.

We analysed the incidence of cattle herd breakdowns due to bovine tuberculosis (Mycobacterium bovis) in relation to experimental badger culling, badger populations and farm characteristics during the Randomized Badger Culling Trial (RBCT). Mixed modelling and event history analysis were used to examine the individual risk factors. The interdependencies of covariates were examined using structural equation modelling. There were consistent findings among the different analyses demonstrating that during a badger culling programme farms experiencing: reactive culling, larger herd sizes, larger holdings and holdings with multiple parcels of land were all at greater risk of a herd breakdown. Proactive culling reduced risks within the culling area, but we did not assess any potential effects in the periphery of the treatment area. Badger-related variables measured prior to the start of culling (number of social groups and length of badger territorial boundaries) did not consistently point to an increase in risk, when set against a background of ongoing badger culling. This could be because (1) the collected variables were not important to risk in cattle, or (2) there were insufficient data to demonstrate their importance. Our findings highlight the difficulty in identifying simple predictors of spatial variation in transmission risks from badger populations and the consequent challenge of tailoring management actions to any such field data.

Epidemiology of squirrelpox virus in grey squirrels in the UK.

The dramatic decline of the native red squirrel in the UK has been attributed to both direct and disease-mediated competition with the grey squirrel where the competitor acts as a reservoir host of squirrelpox virus (SQPV). SQPV is threatening red squirrel conservation efforts, yet little is known about its epidemiology. We analysed seroprevalence of antibody against SQPV in grey squirrels from northern England and the Scottish Borders in relation to season, weather, sex, and body weight using Generalized Linear Models in conjunction with Structural Equation Modelling. Results indicated a heterogeneous prevalence pattern which is male-biased, increases with weight and varies seasonally. Seroprevalence rose during the autumn and peaked in spring. Weather parameters had an indirect effect on SQPV antibody status. Our findings point towards a direct disease transmission route, which includes environmental contamination. Red squirrel conservation management options should therefore seek to minimize squirrel contact points.

Top predators, mesopredators and their prey: interference ecosystems along bioclimatic productivity gradients.

1. The Mesopredator Release Hypothesis (MRH) suggests that top predator suppression of mesopredators is a key ecosystem function with cascading impacts on herbivore prey, but it remains to be shown that this top-down cascade impacts the large-scale structure of ecosystems. 2. The Exploitation Ecosystems Hypothesis (EEH) predicts that regional ecosystem structures are determined by top-down exploitation and bottom-up productivity. In contrast to MRH, EEH assumes that interference among predators has a negligible impact on the structure of ecosystems with three trophic levels. 3. We use the recolonization of a top predator in a three-level boreal ecosystem as a natural experiment to test if large-scale biomass distributions and population trends support MRH. Inspired by EEH, we also test if top-down interference and bottom-up productivity impact regional ecosystem structures. 4. We use data from the Finnish Wildlife Triangle Scheme which has monitored top predator (lynx, Lynx lynx), mesopredator (red fox, Vulpes vulpes) and prey (mountain hare, Lepus timidus) abundance for 17 years in a 200 000 km(2) study area which covers a distinct productivity gradient. 5. Fox biomass was lower than expected from productivity where lynx biomass was high, whilst hare biomass was lower than expected from productivity where fox biomass was high. Hence, where interference controlled fox abundance, lynx had an indirect positive impact on hare abundance as predicted by MRH. The rates of change indicated that lynx expansion gradually suppressed fox biomass. 6. Lynx status caused shifts between ecosystem structures. In the 'interference ecosystem', lynx and hare biomass increased with productivity whilst fox biomass did not. In the 'mesopredator release ecosystem', fox biomass increased with productivity but hare biomass did not. Thus, biomass controlled top-down did not respond to changes in productivity. This fulfils a critical prediction of EEH. 7. We conclude that the cascade involving top predators, mesopredators and their prey can determine large-scale biomass distribution patterns and regional ecosystem structures. Hence, interference within trophic levels has to be taken into account to understand how terrestrial ecosystem structures are shaped.

The transmission of nosocomial pathogens in an intensive care unit: a space-time clustering and structural equation modelling approach.

We investigated the incidence of cases of nosocomial pathogens and risk factors in an intensive treatment unit ward to determine if the number of cases is dependent on location of patients and the colonization/infection history of the ward. A clustering approach method was developed to investigate the patterns of spread of cases through time for five microorganisms [methicillin-resistant Staphylococcus aureus (MRSA), Acinetobacter spp., Klebsiella spp., Candida spp., and Pseudomonas aeruginosa] using hospital microbiological monitoring data and ward records of patient-bed use. Cases of colonization/infection by MRSA, Candida and Pseudomonas were clustered in beds and through time while cases of Klebsiella and Acinetobacter were not. We used structural equation modelling to analyse interacting risk factors and the potential pathways of transmission in the ward. Prior nurse contact with colonized/infected patients, mediated by the number of patient-bed movements, were important predictors for all cases, except for those of Pseudomonas. General health and invasive surgery were significant predictors of cases of Candida and Klebsiella. We suggest that isolation and bed movement as a strategy to manage MRSA infections is likely to impact upon the incidence of cases of other opportunist pathogens.

Campylobacter in housed broiler chickens: a longitudinal study of risk factors.

Infections by Campylobacter spp. are a major cause of gastrointestinal disease in the United Kingdom. Most cases are associated with the consumption of chicken that has become contaminated during production. We investigated the epidemiology of Campylobacter spp. in chickens in a 3-year longitudinal study of flocks reared on 30 farms in the United Kingdom. We used Generalized Linear Mixed Effect Models (GLMM) to investigate putative risk factors associated with incidence and prevalence of flock infection arising from farm and flock management and local environmental conditions during rearing. We used survival analysis to investigate infection events and associated risk factors over the course of the study using two marginal models - the independent increment approach, which assumed that individual infection events were independent; and a conditional approach, which assumed that events were conditional on those preceding. Models of flock prevalence were highly overdispersed suggesting that infection within flocks was aggregated. The key predictors of flock infection identified from the GLMM analyses were mean temperature and mean rainfall in the month of slaughter and also the presence of natural ventilation. Mean temperature in the month of slaughter was also a significant predictor of flock infection, although the analyses suggested that the risk in flocks increased in a unimodal way in relation to temperature, peaking at 12 degrees C. The extent of pad burn was also identified as a predictor in these analyses. We conclude that predicting prevalence within flocks with linear modelling approaches is likely to be difficult, but that it may be possible to predict when flocks are at risk of Campylobacter infection. This is a key first step in managing disease and reducing the risks posed to the human food chain.

The epidemiology of atypical mycobacterial diseases in northern England: a space-time clustering and Generalized Linear Modelling approach.

The incidence of infection by mycobacteria, other than tubercle bacilli (MOTT) is increasing in the United Kingdom, Europe and the United States. These diseases increase morbidity and are an increasing public health concern. However, the epidemiology of disease due to these species is not well characterized. We used space-time clustering approaches and Generalized Linear Modelling to investigate the potential predictors of disease in cases of infection by organisms of the Mycobacterium avium complex (MAC) and M. malmoense recorded in the north of England during 2000-2005. There was significant spatial and temporal clustering in juvenile cases of infection by MAC but not for cases of infection in adults by either species. There were no significant predictors of infection by M. malmoense or juvenile cases of M. avium. Incidence of disease caused by M. avium in adults was significantly related to health deprivation and weakly related to rainfall. We consider possible reasons for the difference in epidemiology in infection by M. avium in adults and juveniles.

Disease threats posed by alien species: the role of a poxvirus in the decline of the native red squirrel in Britain.

Red squirrels are declining in the United Kingdom. Competition from, and squirrel poxvirus (SQPV) disease carried by, grey squirrels are assumed to be determining the decline. We analyse the incidence of disease and changes in distribution of the two species in Cumbria, from 1993 to 2003 and compare these to the predictions of an individual-based (IB) spatially explicit disease model simulating the dynamics of both squirrel species and SQPV in the landscape. Grey squirrels increased whilst red squirrels declined over 10 years. The incidence of disease in red squirrels was related to the time since grey squirrels arrived in the landscape. Analysis of rates of decline in red squirrel populations in other areas showed that declines are 17-25 times higher in regions where SQPV is present in grey squirrel populations than in those where it is not. The IB model predicted spatial overlap of 3-4 years between the species that was also observed in the field. The model predictions matched the observed data best when contact rates and rates of infection between the two species were low. The model predicted that a grey squirrel population control of >60% effective kill was needed to stop the decline in red squirrel populations in Cumbria.

Where diseases and networks collide: lessons to be learnt from a study of the 2001 foot-and-mouth disease epidemic.

This paper uses a graph-theoretical approach to investigate the properties of the observed network of disease transmission in the 2001 foot-and-mouth epidemic in the United Kingdom. This analysis revealed both global and local heterogeneity in the contact pattern between the infected premises in the first 3 weeks of the disease. In particular, the global heterogeneity contributed to the failure of the culling strategy imposed by the UK government. However, a more effective strategy targeting selective deletion of key premises in the network was not available once the epidemic had begun. We recommend that post-hoc analyses of this sort should become part of preventative and proactive policy rather than part of a reaction to an ongoing crisis.

Predicting the distribution of ground beetle species (Coleoptera, Carabidae) in Britain using land cover variables.

Predictions of plant and animal species distributions are important for conservation and for the assessment of large-scale ecosystem change. Land cover data are becoming more widely available for use in land management and conservation. We use a logistic regression modelling approach to investigate the utility of these data for modelling. The relationship between the distribution of 137 British ground beetles species and land cover was investigated using data from 1,687 10 km national grid squares. Land cover data were simplified using ordination and the axes used as predictors in logistic regression with presence absence data for individual beetle species as response variables. Significant regression models were generated for all species with first and second axis scores. The amounts of variation explained by models were generally low, but predictions derived from models generally matched the known distributions of the species in Britain. Species with coastal preferences were poorly modelled and predicted to occur throughout lowland Britain whilst a number of species occurring in southern Britain were predicted to occur into Scotland. A validation exercise comparing model predictions with new data from a survey of 59 10 km(2) produced mixed results with the distribution of grassland species being better predicted than riverine species. Jack-knifing was used to assess the robustness of models for four species which differed in their apparent responses to the land cover variables. Methods for improving the predictive power of these models and their potential for use in assessing the impact of global climate change are discussed.