LIMPRINT: prevalence of chronic edema in health services in Copenhagen, Denmark

Background: The International Lymphedema Framework developed an international study, Lymphedema Impact and Prevalence International (LIMPRINT) to estimate the prevalence and impact of chronic edema in heterogeneous populations. Methods and results: A validation study using the LIMPRINT methodology was undertaken in Denmark. Participants with CO were identified from in-patient services and compared to those identified within a specialist lymphoedema service and 3 primary care settings. Of 452 inpatients available for screening CO was present in 177(39%) and absent in 275(61%). In addition, 723 participants were found from specialist and primary care services (LPCS). In-patients were significantly older and more likely to be underweight or normal weight. They were more likely to suffer from heart failure/IHD (44.6% vs 23.4%, p<0.001) and have neurological problems (18.1% vs 10.9% p=0.009). The inpatient group were nearly all suffering from secondary Lymphoedema and were less likely to have a cancer or venous diagnosis, but more likely to have immobility as the cause of CO (44.0% vs 17.7%, p<0.001). No in-patients had midline CO compared to 30 within LPCS. Fewer in the in-patient group had standard CO treatment (17.1% vs 73.5%, p<0.001) and subjective control of swelling was worse (19.9% vs 66.7%, p<0.001). Whilst the in-patient group experienced fewer acute infections, when they did so, they were more likely to be admitted to hospital for this (78.6% vs 51.0%, p=0.049). Conclusion: The prevalence of CO in inpatient facilities is high and those with CO have multiple comorbidities that vary according to setting. The feasibility study showed the methodology could be adapted for use in different health systems

A reassuring presence: An evaluation of Bradford District Hospice at Home service

Within the United Kingdom, a developing role for primary care services in cancer and palliative care has resulted in an increase in palliative home care teams. The provision of professional care in the home setting seeks to provide necessary services and enhanced choice for patients whose preference is to die at home. A mismatch between patient preference for home death and the actual number of people who died at home was identified within Bradford, the locality of this study. In response to this mismatch, and reflecting the policy environment of wishing to enhance community service provision, the four Primary Care Trusts (PCTs) in the city sought to offer support to patients who wished to remain in their own homes through the final stages of a terminal illness. To offer this support they set up a dedicated hospice at home team. This would provide services and support for patients in achieving a dignified, symptom free and peaceful death, allowing families to maximise time spent together. The aim of the study was to evaluate the Bradford hospice at home service from the perspective of carers, nurses and General Practitioners. Postal questionnaires were sent to carers (n = 289), district nurses (n = 508) and GP's (n = 444) using Bradford's hospice at home service. Resulting quantitative data was analysed using the Statical Package for Social Sciences (SPSS) and qualitative data was analysed using grounded theory techniques. The data from carers, district nurses and GPs provide general support for the Bradford hospice at home service. Carers valued highly the opportunity to 'fulfil a promise' to the individual who wished to be cared for at home. District nurses and GPs cited the positive impact of access to specialist expertise. This was a 'reassuring presence' for primary healthcare teams and offered 'relief of carer anxiety' by providing prompt, accessible and sensitive care. Carers and health professionals welcomed the increased possibility of patients being cared for at home. The study identified the need to focus on improving skill levels of staff and on ensuring continuity of care

Prevalence and risk factors for chronic edema in U.K. community nursing services

Background and study design: Chronic edema (CO) is believed to be a major clinical problem within community nursing services in the UK. This study was undertaken as part of the LIMPRINT international study to determine the number of people with chronic oedema and its impact on health services. Methods and Results: Three urban based community nursing services participated in the UK with prospective evaluation over 4 weeks of all patients receiving nursing care using a questionnaire-based interview and clinical assessment using the LIMPRINT tools. Of the total 2,541 assessed 1,440 (56.7%) were considered to have CO, comprising Leicester City (768/ 1298 (59.2%), Nottingham West (124/ 181 (68.5%)) and Nottingham City (548/1062 (51.6%)). The mean age for women with CO was 78.6 (SD 12.8) years and for men 72.9 (SD14.5). More patients with CO suffered from diabetes (32.1% versus 27.9%, p=0.027), heart failure/ ischaemic heart disease (27.3% versus 14.0%, p<0.001) and peripheral arterial occlusive disease (5.5% versus 1.9%, p<0.001). By far the greatest association was with the presence of a wound (73.6% versus 37.9%, p<0.001). Cellulitis affected 628 (24.7%) and 688 (47.8%) had a concurrent leg ulcer. Rates of reduced mobility (71.6% versus 61.9%) and obesity were higher in those with CO. Six independent factors associated with chronic oedema were service location, age, ethnicity, obesity, heart failure and the presence of a wound. Conclusion: Chronic oedema is a major and growing health care problem within primary care that has been previously unrecognised and requires effective service provision

A Dynamic Model of Interactions of Ca^(2+), Calmodulin, and Catalytic Subunits of Ca^(2+)/Calmodulin-Dependent Protein Kinase II

During the acquisition of memories, influx of Ca^(2+) into the postsynaptic spine through the pores of activated N-methyl-D-aspartate-type glutamate receptors triggers processes that change the strength of excitatory synapses. The pattern of Ca^(2+) influx during the first few seconds of activity is interpreted within the Ca^(2+)-dependent signaling network such that synaptic strength is eventually either potentiated or depressed. Many of the critical signaling enzymes that control synaptic plasticity, including Ca^(2+)/calmodulin-dependent protein kinase II (CaMKII), are regulated by calmodulin, a small protein that can bind up to 4 Ca^(2+) ions. As a first step toward clarifying how the Ca^(2+)-signaling network decides between potentiation or depression, we have created a kinetic model of the interactions of Ca^(2+), calmodulin, and CaMKII that represents our best understanding of the dynamics of these interactions under conditions that resemble those in a postsynaptic spine. We constrained parameters of the model from data in the literature, or from our own measurements, and then predicted time courses of activation and autophosphorylation of CaMKII under a variety of conditions. Simulations showed that species of calmodulin with fewer than four bound Ca^(2+) play a significant role in activation of CaMKII in the physiological regime, supporting the notion that processing ofCa^(2+) signals in a spine involves competition among target enzymes for binding to unsaturated species of CaM in an environment in which the concentration of Ca^(2+) is fluctuating rapidly. Indeed, we showed that dependence of activation on the frequency of Ca^(2+) transients arises from the kinetics of interaction of fluctuating Ca^(2+) with calmodulin/CaMKII complexes. We used parameter sensitivity analysis to identify which parameters will be most beneficial to measure more carefully to improve the accuracy of predictions. This model provides a quantitative base from which to build more complex dynamic models of postsynaptic signal transduction during learning

Midday measurements of leaf water potential and stomatal conductance are highly correlated with daily water use of Thompson Seedless grapevines

A study was conducted to determine the relationship between midday measurements of vine water status and daily water use of grapevines measured with a weighing lysimeter. Water applications to the vines were terminated on August 24th for 9 days and again on September 14th for 22 days. Daily water use of the vines in the lysimeter (ETLYS) was approximately 40 L vine−1 (5.3 mm) prior to turning the pump off, and it decreased to 22.3 L vine−1 by September 2nd. Pre-dawn leaf water potential (ΨPD) and midday Ψl on August 24th were −0.075 and −0.76 MPa, respectively, with midday Ψl decreasing to −1.28 MPa on September 2nd. Leaf g s decreased from ~500 to ~200 mmol m−2 s−1 during the two dry-down periods. Midday measurements of g s and Ψl were significantly correlated with one another (r = 0.96) and both with ETLYS/ETo (r = ~0.9). The decreases in Ψl, g s, and ETLYS/ETo in this study were also a linear function of the decrease in volumetric soil water content. The results indicate that even modest water stress can greatly reduce grapevine water use and that short-term measures of vine water status taken at midday are a reflection of daily grapevine water us

Clinical and ethical challenges in undertaking LIMPRINT in vulnerable populations

Background and study objective: To estimate the prevalence of CO and wounds within two vulnerable populations a male, high security prison in the East Midlands (UK) and residential and nursing homes in the UK and Australia. Methods and results: Methods for screening for chronic oedema (CO) and wounds were adapted from the main LIMPRINT methodology. Prison population. In total, 195 inmates were recruited with 22(11%) having CO. While the majority were white Caucasian (156 / 83.4%) a further 20 (10.7%) were dark skinned with 11 (5.95%) from other minority populations. Co-morbidities included 123 (63%) smokers, 22 (11%) alcohol dependant, 60 (31%) with mental health problems and 35 (18%) a history of self- harm. Only three had a current wound with 30 (16%) having had a traumatic stab wound. Residential and nursing homes (UK and Australia): In the UK, the total population available for inclusion was 189 with only 137(73%) recruited. Seventy two of the 137 (52%) suffered from CO and a further 16 (23%) had a history of cellulitis. Results from the Australian residential care facilities have been published in full. In summary, of the 37 participants 20 (54%) experienced CO with 25 (68%) having co-morbidities and 11 (30%) having a concurrent wound. Conclusion: Obtaining an accurate picture of the prevalence and impact of CO in vulnerable populations is extremely challenging due issues of access and consent. Lack of reliable data for these populations will contribute to poor service provision

Can we derive an 'exchange rate' between descriptive and preference-based outcome measures for stroke? Results from the transfer to utility (TTU) technique

<p>Abstract</p> <p>Background</p> <p>Stroke-specific outcome measures and descriptive measures of health-related quality of life (HRQoL) are unsuitable for informing decision-makers of the broader consequences of increasing or decreasing funding for stroke interventions. The quality-adjusted life year (QALY) provides a common metric for comparing interventions over multiple dimensions of HRQoL and mortality differentials. There are, however, many circumstances when – because of timing, lack of foresight or cost considerations – only stroke-specific or descriptive measures of health status are available and some indirect means of obtaining QALY-weights becomes necessary. In such circumstances, the use of regression-based transformations or mappings can circumvent the failure to elicit QALY-weights by allowing predicted weights to proxy for observed weights. This regression-based approach has been dubbed 'Transfer to Utility' (TTU) regression. The purpose of the present study is to demonstrate the feasibility and value of TTU regression in stroke by deriving transformations or mappings from stroke-specific and generic but descriptive measures of health status to a generic preference-based measure of HRQoL in a sample of Australians with a diagnosis of acute stroke. Findings will quantify the additional error associated with the use of condition-specific to generic transformations in stroke.</p> <p>Methods</p> <p>We used TTU regression to derive empirical transformations from three commonly used descriptive measures of health status for stroke (NIHSS, Barthel and SF-36) to a preference-based measure (AQoL) suitable for attaching QALY-weights to stroke disease states; based on 2570 observations drawn from a sample of 859 patients with stroke.</p> <p>Results</p> <p>Transformations from the SF-36 to the AQoL explained up to 71.5% of variation in observed AQoL scores. Differences between mean predicted and mean observed AQoL scores from the 'severity-specific' item- and subscale-based SF-36 algorithms and from the 'moderate to severe' index- and item-based Barthel algorithm were neither clinically nor statistically significant when 'low severity' SF-36 transformations were used to predict AQoL scores for patients in the NIHSS = 0 and NIHSS = 1–5 subgroups and when 'moderate to severe severity' transformations were used to predict AQoL scores for patients in the NIHSS ≥ 6 subgroup. In contrast, the difference between mean predicted and mean observed AQoL scores from the NIHSS algorithms and from the 'low severity' Barthel algorithms reached levels that could mask minimally important differences on the AQoL scale.</p> <p>Conclusion</p> <p>While our NIHSS to AQoL transformations proved unsuitable for most applications, our findings demonstrate that stroke-relevant outcome measures such as the SF-36 and Barthel Index can be adequately transformed to preference-based measures for the purposes of economic evaluation.</p

Does present use of cardiovascular medication reflect elevated cardiovascular risk scores estimated ten years ago? A population based longitudinal observational study

Background It is desirable that those at highest risk of cardiovascular disease should have priority for preventive measures, eg. treatment with prescription drugs to modify their risk. We wanted to investigate to what extent present use of cardiovascular medication (CVM) correlates with cardiovascular risk estimated by three different risk scores (Framingham, SCORE and NORRISK) ten years ago. Methods Prospective logitudinal observational study of 20 252 participants in The Hordaland Health Study born 1950-57, not using CVM in 1997-99. Prescription data obtained from The Norwegian Prescription Database in 2008. Results 26% of men and 22% of women aged 51-58 years had started to use some CVM during the previous decade. As a group, persons using CVM scored significantly higher on the risk algorithms Framingham, SCORE and NORRISK compared to those not treated. 16-20% of men and 20-22% of women with risk scores below the high-risk thresholds for the three risk scores were treated with CVM, while 60-65% of men and 25-45% of women with scores above the high-risk thresholds received no treatment. Among women using CVM, only 2.2% (NORRISK), 4.4% (SCORE) and 14.5% (Framingham) had risk scores above the high-risk values. Low education, poor self-reported general health, muscular pains, mental distress (in females only) and a family history of premature cardiovascular disease correlated with use of CVM. Elevated blood pressure was the single factor most strongly predictive of CVM treatment. Conclusion Prescription of CVM to middle-aged individuals by large seems to occur independently of estimated total cardiovascular risk, and this applies especially to females

Meredys, a multi-compartment reaction-diffusion simulator using multistate realistic molecular complexes

<p>Abstract</p> <p>Background</p> <p>Most cellular signal transduction mechanisms depend on a few molecular partners whose roles depend on their position and movement in relation to the input signal. This movement can follow various rules and take place in different compartments. Additionally, the molecules can form transient complexes. Complexation and signal transduction depend on the specific states partners and complexes adopt. Several spatial simulator have been developed to date, but none are able to model reaction-diffusion of realistic multi-state transient complexes.</p> <p>Results</p> <p><it>Meredys </it>allows for the simulation of multi-component, multi-feature state molecular species in two and three dimensions. Several compartments can be defined with different diffusion and boundary properties. The software employs a Brownian dynamics engine to simulate reaction-diffusion systems at the reactive particle level, based on compartment properties, complex structure, and hydro-dynamic radii. Zeroth-, first-, and second order reactions are supported. The molecular complexes have realistic geometries. Reactive species can contain user-defined feature states which can modify reaction rates and outcome. Models are defined in a versatile NeuroML input file. The simulation volume can be split in subvolumes to speed up run-time.</p> <p>Conclusions</p> <p><it>Meredys </it>provides a powerful and versatile way to run accurate simulations of molecular and sub-cellular systems, that complement existing multi-agent simulation systems. <it>Meredys </it>is a Free Software and the source code is available at <url>http://meredys.sourceforge.net/</url>.</p