Disease prevention versus data privacy : using landcover maps to inform spatial epidemic models

The availability of epidemiological data in the early stages of an outbreak of an infectious disease is vital for modelers to make accurate predictions regarding the likely spread of disease and preferred intervention strategies. However, in some countries, the necessary demographic data are only available at an aggregate scale. We investigated the ability of models of livestock infectious diseases to predict epidemic spread and obtain optimal control policies in the event of imperfect, aggregated data. Taking a geographic information approach, we used land cover data to predict UK farm locations and investigated the influence of using these synthetic location data sets upon epidemiological predictions in the event of an outbreak of foot-and-mouth disease. When broadly classified land cover data were used to create synthetic farm locations, model predictions deviated significantly from those simulated on true data. However, when more resolved subclass land use data were used, moderate to highly accurate predictions of epidemic size, duration and optimal vaccination and ring culling strategies were obtained. This suggests that a geographic information approach may be useful where individual farm-level data are not available, to allow predictive analyses to be carried out regarding the likely spread of disease. This method can also be used for contingency planning in collaboration with policy makers to determine preferred control strategies in the event of a future outbreak of infectious disease in livestock

Effectiveness and cost-effectiveness of an educational intervention for practice teams to deliver problem focused therapy for insomnia: rationale and design of a pilot cluster randomised trial

Background: Sleep problems are common, affecting over a third of adults in the United Kingdom and leading to reduced productivity and impaired health-related quality of life. Many of those whose lives are affected seek medical help from primary care. Drug treatment is ineffective long term. Psychological methods for managing sleep problems, including cognitive behavioural therapy for insomnia (CBTi) have been shown to be effective and cost effective but have not been widely implemented or evaluated in a general practice setting where they are most likely to be needed and most appropriately delivered. This paper outlines the protocol for a pilot study designed to evaluate the effectiveness and cost-effectiveness of an educational intervention for general practitioners, primary care nurses and other members of the primary care team to deliver problem focused therapy to adult patients presenting with sleep problems due to lifestyle causes, pain or mild to moderate depression or anxiety. Methods and design: This will be a pilot cluster randomised controlled trial of a complex intervention. General practices will be randomised to an educational intervention for problem focused therapy which includes a consultation approach comprising careful assessment (using assessment of secondary causes, sleep diaries and severity) and use of modified CBTi for insomnia in the consultation compared with usual care (general advice on sleep hygiene and pharmacotherapy with hypnotic drugs). Clinicians randomised to the intervention will receive an educational intervention (2 × 2 hours) to implement a complex intervention of problem focused therapy. Clinicians randomised to the control group will receive reinforcement of usual care with sleep hygiene advice. Outcomes will be assessed via self-completion questionnaires and telephone interviews of patients and staff as well as clinical records for interventions and prescribing. Discussion: Previous studies in adults have shown that psychological treatments for insomnia administered by specialist nurses to groups of patients can be effective within a primary care setting. This will be a pilot study to determine whether an educational intervention aimed at primary care teams to deliver problem focused therapy for insomnia can improve sleep management and outcomes for individual adult patients presenting to general practice. The study will also test procedures and collect information in preparation for a larger definitive cluster-randomised trial. The study is funded by The Health Foundation

Mechanisms of Cognitive Impairment in Cerebral Small Vessel Disease: Multimodal MRI Results from the St George's Cognition and Neuroimaging in Stroke (SCANS) Study.

Cerebral small vessel disease (SVD) is a common cause of vascular cognitive impairment. A number of disease features can be assessed on MRI including lacunar infarcts, T2 lesion volume, brain atrophy, and cerebral microbleeds. In addition, diffusion tensor imaging (DTI) is sensitive to disruption of white matter ultrastructure, and recently it has been suggested that additional information on the pattern of damage may be obtained from axial diffusivity, a proposed marker of axonal damage, and radial diffusivity, an indicator of demyelination. We determined the contribution of these whole brain MRI markers to cognitive impairment in SVD. Consecutive patients with lacunar stroke and confluent leukoaraiosis were recruited into the ongoing SCANS study of cognitive impairment in SVD (n = 115), and underwent neuropsychological assessment and multimodal MRI. SVD subjects displayed poor performance on tests of executive function and processing speed. In the SVD group brain volume was lower, white matter hyperintensity volume higher and all diffusion characteristics differed significantly from control subjects (n = 50). On multi-predictor analysis independent predictors of executive function in SVD were lacunar infarct count and diffusivity of normal appearing white matter on DTI. Independent predictors of processing speed were lacunar infarct count and brain atrophy. Radial diffusivity was a stronger DTI predictor than axial diffusivity, suggesting ischaemic demyelination, seen neuropathologically in SVD, may be an important predictor of cognitive impairment in SVD. Our study provides information on the mechanism of cognitive impairment in SVD

Epidemiology of Subpatent Plasmodium Falciparum Infection: Implications for Detection of Hotspots with Imperfect Diagnostics.

At the local level, malaria transmission clusters in hotspots, which may be a group of households that experience higher than average exposure to infectious mosquitoes. Active case detection often relying on rapid diagnostic tests for mass screen and treat campaigns has been proposed as a method to detect and treat individuals in hotspots. Data from a cross-sectional survey conducted in north-western Tanzania were used to examine the spatial distribution of Plasmodium falciparum and the relationship between household exposure and parasite density. Dried blood spots were collected from consenting individuals from four villages during a survey conducted in 2010. These were analysed by PCR for the presence of P. falciparum, with the parasite density of positive samples being estimated by quantitative PCR. Household exposure was estimated using the distance-weighted PCR prevalence of infection. Parasite density simulations were used to estimate the proportion of infections that would be treated using a screen and treat approach with rapid diagnostic tests (RDT) compared to targeted mass drug administration (tMDA) and Mass Drug Administration (MDA). Polymerase chain reaction PCR analysis revealed that of the 3,057 blood samples analysed, 1,078 were positive. Mean distance-weighted PCR prevalence per household was 34.5%. Parasite density was negatively associated with transmission intensity with the odds of an infection being subpatent increasing with household exposure (OR 1.09 per 1% increase in exposure). Parasite density was also related to age, being highest in children five to ten years old and lowest in those > 40 years. Simulations of different tMDA strategies showed that treating all individuals in households where RDT prevalence was above 20% increased the number of infections that would have been treated from 43 to 55%. However, even with this strategy, 45% of infections remained untreated. The negative relationship between household exposure and parasite density suggests that DNA-based detection of parasites is needed to provide adequate sensitivity in hotspots. Targeting MDA only to households with RDT-positive individuals may allow a larger fraction of infections to be treated. These results suggest that community-wide MDA, instead of screen and treat strategies, may be needed to successfully treat the asymptomatic, subpatent parasite reservoir and reduce transmission in similar settings

Stroke genetics: prospects for personalized medicine.

Epidemiologic evidence supports a genetic predisposition to stroke. Recent advances, primarily using the genome-wide association study approach, are transforming what we know about the genetics of multifactorial stroke, and are identifying novel stroke genes. The current findings are consistent with different stroke subtypes having different genetic architecture. These discoveries may identify novel pathways involved in stroke pathogenesis, and suggest new treatment approaches. However, the already identified genetic variants explain only a small proportion of overall stroke risk, and therefore are not currently useful in predicting risk for the individual patient. Such risk prediction may become a reality as identification of a greater number of stroke risk variants that explain the majority of genetic risk proceeds, and perhaps when information on rare variants, identified by whole-genome sequencing, is also incorporated into risk algorithms. Pharmacogenomics may offer the potential for earlier implementation of 'personalized genetic' medicine. Genetic variants affecting clopidogrel and warfarin metabolism may identify non-responders and reduce side-effects, but these approaches have not yet been widely adopted in clinical practice

Evaluation of Protocol Uniformity Concerning Laparoscopic Cholecystectomy in The Netherlands

Background: Iatrogenic bile duct injury remains a current complication of laparoscopic cholecystectomy. One uniform and standardized protocol, based on the "critical view of safety" concept of Strasberg, should red

Persistent anthrax as a major driver of wildlife mortality in a tropical rainforest

Anthrax is a globally important animal disease and zoonosis. Despite this, our current knowledge of anthrax ecology is largely limited to arid ecosystems, where outbreaks are most commonly reported. Here we show that the dynamics of an anthrax-causing agent, Bacillus cereus biovar anthracis, in a tropical rainforest have severe consequences for local wildlife communities. Using data and samples collected over three decades, we show that rainforest anthrax is a persistent and widespread cause of death for a broad range of mammalian hosts. We predict that this pathogen will accelerate the decline and possibly result in the extirpation of local chimpanzee (Pan troglodytes verus) populations. We present the epidemiology of a cryptic pathogen and show that its presence has important implications for conservation

Telomeres are shorter in myocardial infarction patients compared to healthy subjects: correlation with environmental risk factors

Shorter telomeres have been reported in premature myocardial infarction (MI) patients. Our work aimed at confirming the association of shorter telomere with MI in two case–control studies and in familial hypercholesterolemia (FH) patients with coronary heart disease (CHD). The HIFMECH study compared 598 white male patients (<60 years) who survived a first MI and 653 age-matched controls from North and South Europe. Additionally, from the UK, 413 coronary artery bypass graft (CABG) patients and two groups of 367 and 94 FH patients, of whom 145 and 17 respectively had premature CHD, were recruited. Leukocyte telomere length (LTL) was measured using a real-time polymerase chain reaction-based method. In HIFMECH, LTL was significantly shorter in subjects from the North (7.99 kb, SD 4.51) compared to the South (8.27 kb, SD 4.14; p = 0.02) and in cases (7.85 kb, SD 4.01) compared to controls (8.04 kb, SD 4.46; p = 0.04). In the CABG study, LTL was significantly shorter (6.89 kb, SD 4.14) compared to the HIFMECH UK controls (7.53, SD 5.29; p = 0.007). In both samples of FH patients, LTL was shorter in those with CHD (overall 8.68 kb, SD 4.65) compared to the non-CHD subjects (9.23 kb, SD 4.83; p = 0.012). Apart from a consistent negative correlation with age, LTL was not associated across studies with any measured CHD risk factors. The present data confirms that subjects with CHD have shorter telomeres than controls and extends this to those with monogenic and polygenic forms of CHD

Acupuncture for pain and osteoarthritis of the knee: a pilot study for an open parallel-arm randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>There is some evidence that acupuncture for pain and osteoarthritis (OA) of the knee is more than a placebo, and short term clinical benefits have been observed when acupuncture is compared to usual care. However there is insufficient evidence on whether clinical benefits of acupuncture are sustained over the longer term. In this study our key objectives are to inform the design parameters for a fully powered pragmatic randomised controlled trial. These objectives include establishing potential recruitment rates, appropriate validated outcome measures, attendance levels for acupuncture treatment, loss to follow up and the sample size for a full scale trial.</p> <p>Methods</p> <p>Potential participants aged over 50 with pain and osteoarthritis of the knee were identified from a GP database. Eligible patients were randomised to either 'acupuncture plus usual care' and 'usual care' alone, with allocation appropriately concealed. Acupuncture consisted of up to 10 sessions usually weekly. Outcome measures included Western Ontario and McMaster Universities (WOMAC) index with the sample size for a full scale trial determined from the variance.</p> <p>Results</p> <p>From the GP database of 15,927 patients, 335 potential trial participants were identified and invited to participate. After screening responses, 78 (23%) were identified as eligible and 30 patients who responded most promptly were randomised to 'acupuncture plus usual care' (15 patients) and 'usual care' alone (15 patients). Attendance for acupuncture appointments was high at 90% of the maximum. Although the trial was not powered to detect significant changes in outcome, the WOMAC pain index showed a statistically significant reduction at 3 months in the acupuncture group compared to usual care. This was not sustained at 12 months. The sample size for a fully powered two-arm trial was estimated to be 350.</p> <p>Conclusion</p> <p>This pilot study provided the evidence that a fully powered study to explore the longer term impact of acupuncture would be worthwhile, and relevant design features for such a trial were determined.</p> <p>Trial registration number</p> <p>ISRCTN25134802.</p

Inefficient Quality Control of Thermosensitive Proteins on the Plasma Membrane

BACKGROUND: Misfolded proteins are generally recognised by cellular quality control machinery, which typically results in their ubiquitination and degradation. For soluble cytoplasmic proteins, degradation is mediated by the proteasome. Membrane proteins that fail to fold correctly are subject to ER associated degradation (ERAD), which involves their extraction from the membrane and subsequent proteasome-dependent destruction. Proteins with abnormal transmembrane domains can also be recognised in the Golgi or endosomal system and targeted for destruction in the vacuole/lysosome. It is much less clear what happens to membrane proteins that reach their destination, such as the cell surface, and then suffer damage. METHODOLOGY/PRINCIPAL FINDINGS: We have tested the ability of yeast cells to degrade membrane proteins to which temperature-sensitive cytoplasmic alleles of the Ura3 protein or of phage lambda repressor have been fused. In soluble form, these proteins are rapidly degraded upon temperature shift, in part due to the action of the Doa10 and San1 ubiquitin ligases and the proteasome. When tethered to the ER protein Use1, they are also degraded. However, when tethered to a plasma membrane protein such as Sso1 they escape degradation, either in the vacuole or by the proteasome. CONCLUSIONS/SIGNIFICANCE: Membrane proteins with a misfolded cytoplasmic domain appear not to be efficiently recognised and degraded once they have escaped the ER, even though their defective domains are exposed to the cytoplasm and potentially to cytoplasmic quality controls. Membrane tethering may provide a way to reduce degradation of unstable proteins