A Discrete Event Simulation model to evaluate the treatment pathways of patients with Cataract in the United Kingdom

Background The number of people affected by cataract in the United Kingdom (UK) is growing rapidly due to ageing population. As the only way to treat cataract is through surgery, there is a high demand for this type of surgery and figures indicate that it is the most performed type of surgery in the UK. The National Health Service (NHS), which provides free of charge care in the UK, is under huge financial pressure due to budget austerity in the last decade. As the number of people affected by the disease is expected to grow significantly in coming years, the aim of this study is to evaluate whether the introduction of new processes and medical technologies will enable cataract services to cope with the demand within the NHS funding constraints. Methods We developed a Discrete Event Simulation model representing the cataract services pathways at Leicester Royal Infirmary Hospital. The model was inputted with data from national and local sources as well as from a surgery demand forecasting model developed in the study. The model was verified and validated with the participation of the cataract services clinical and management teams. Results Four scenarios involving increased number of surgeries per half-day surgery theatre slot were simulated. Results indicate that the total number of surgeries per year could be increased by 40% at no extra cost. However, the rate of improvement decreases for increased number of surgeries per half-day surgery theatre slot due to a higher number of cancelled surgeries. Productivity is expected to improve as the total number of doctors and nurses hours will increase by 5 and 12% respectively. However, non-human resources such as pre-surgery rooms and post-surgery recovery chairs are under-utilized across all scenarios. Conclusions Using new processes and medical technologies for cataract surgery is a promising way to deal with the expected higher demand especially as this could be achieved with limited impact on costs. Non-human resources capacity need to be evenly levelled across the surgery pathway to improve their utilisation. The performance of cataract services could be improved by better communication with and proactive management of patients.Peer reviewedFinal Published versio

Aberrant Insertion of the Right Subclavian Artery: an Unusual Cause of Dysphagia in an Adult

Contains fulltext : 79615.pdf (publisher's version ) (Closed access

Foodways in transition: food plants, diet and local perceptions of change in a Costa Rican Ngäbe community

Background Indigenous populations are undergoing rapid ethnobiological, nutritional and socioeconomic transitions while being increasingly integrated into modernizing societies. To better understand the dynamics of these transitions, this article aims to characterize the cultural domain of food plants and analyze its relation with current day diets, and the local perceptions of changes given amongst the Ngäbe people of Southern Conte-Burica, Costa Rica, as production of food plants by its residents is hypothesized to be drastically in recession with an decreased local production in the area and new conservation and development paradigms being implemented. Methods Extensive freelisting, interviews and workshops were used to collect the data from 72 participants on their knowledge of food plants, their current dietary practices and their perceptions of change in local foodways, while cultural domain analysis, descriptive statistical analyses and development of fundamental explanatory themes were employed to analyze the data. Results Results show a food plants domain composed of 140 species, of which 85 % grow in the area, with a medium level of cultural consensus, and some age-based variation. Although many plants still grow in the area, in many key species a decrease on local production–even abandonment–was found, with much reduced cultivation areas. Yet, the domain appears to be largely theoretical, with little evidence of use; and the diet today is predominantly dependent on foods bought from the store (more than 50 % of basic ingredients), many of which were not salient or not even recognized as ‘food plants’ in freelists exercises. While changes in the importance of food plants were largely deemed a result of changes in cultural preferences for store bought processed food stuffs and changing values associated with farming and being food self-sufficient, Ngäbe were also aware of how changing household livelihood activities, and the subsequent loss of knowledge and use of food plants, were in fact being driven by changes in social and political policies, despite increases in forest cover and biodiversity. Conclusions Ngäbe foodways are changing in different and somewhat disconnected ways: knowledge of food plants is varied, reflecting most relevant changes in dietary practices such as lower cultivation areas and greater dependence on food from stores by all families. We attribute dietary shifts to socioeconomic and political changes in recent decades, in particular to a reduction of local production of food, new economic structures and agents related to the State and globalization

Interaction of Polysialic Acid with CCL21 Regulates the Migratory Capacity of Human Dendritic Cells

Dendritic cells (DCs) are the most potent antigen-presenting cells (APCs). Immature DCs (iDCs) are situated in the periphery where they capture pathogen. Subsequently, they migrate as mature DCs (mDCs) to draining lymph nodes to activate T cells. CCR7 and CCL21 contribute to the migratory capacity of the DC, but it is not completely understood what molecular requirements are involved. Here we demonstrate that monocyte-derived DCs dramatically change ST8Sia IV expression during maturation, leading to the generation of polysialic acid (polySia). PolySia expression is highly upregulated after 2 days Toll-like receptor-4 (TLR4) triggering. Surprisingly, only immunogenic and not tolerogenic mDCs upregulated polySia expression. Furthermore, we show that polySia expression on DCs is required for CCL21-directed migration, whereby polySia directly captures CCL21. Corresponding to polySia, the expression level of CCR7 is maximal two days after TLR4 triggering. In contrast, although TLR agonists other than LPS induce upregulation of CCR7, they achieve only a moderate polySia expression. In situ we could detect polySia-expressing APCs in the T cell zone of the lymph node and in the deep dermis. Together our results indicate that prolonged TLR4 engagement is required for the generation of polySia-expressing DCs that facilitate CCL21 capture and subsequent CCL21-directed migration

Epilepsy Caused by an Abnormal Alternative Splicing with Dosage Effect of the SV2A Gene in a Chicken Model

Photosensitive reflex epilepsy is caused by the combination of an individual's enhanced sensitivity with relevant light stimuli, such as stroboscopic lights or video games. This is the most common reflex epilepsy in humans; it is characterized by the photoparoxysmal response, which is an abnormal electroencephalographic reaction, and seizures triggered by intermittent light stimulation. Here, by using genetic mapping, sequencing and functional analyses, we report that a mutation in the acceptor site of the second intron of SV2A (the gene encoding synaptic vesicle glycoprotein 2A) is causing photosensitive reflex epilepsy in a unique vertebrate model, the Fepi chicken strain, a spontaneous model where the neurological disorder is inherited as an autosomal recessive mutation. This mutation causes an aberrant splicing event and significantly reduces the level of SV2A mRNA in homozygous carriers. Levetiracetam, a second generation antiepileptic drug, is known to bind SV2A, and SV2A knock-out mice develop seizures soon after birth and usually die within three weeks. The Fepi chicken survives to adulthood and responds to levetiracetam, suggesting that the low-level expression of SV2A in these animals is sufficient to allow survival, but does not protect against seizures. Thus, the Fepi chicken model shows that the role of the SV2A pathway in the brain is conserved between birds and mammals, in spite of a large phylogenetic distance. The Fepi model appears particularly useful for further studies of physiopathology of reflex epilepsy, in comparison with induced models of epilepsy in rodents. Consequently, SV2A is a very attractive candidate gene for analysis in the context of both mono- and polygenic generalized epilepsies in humans

Canadian physiotherapists' views on certification, specialisation, extended role practice, and entry-level training in rheumatology

<p>Abstract</p> <p>Background</p> <p>Since the last decade there has been a gradual change of boundaries of health professions in providing arthritis care. In Canada, some facilities have begun to adopt new arthritis care models, some of which involve physiotherapists (PT) working in extended roles. However, little is known about PTs' interests in these new roles. The primary objective of this survey was to determine the interests among orthopaedic physiotherapists (PTs) in being a certified arthritis therapist, a PT specialized in arthritis, or an extended scope practitioner in rheumatology, and to explore the associated factors, including the coverage of arthritis content in the entry-level physiotherapy training.</p> <p>Methods</p> <p>Six hundred PTs practicing in orthopaedics in Canada were randomly selected to receive a postal survey. The questionnaire covered areas related to clinical practice, perceptions of rheumatology training received, and attitudes toward PT roles in arthritis care. Logistic regression models were developed to explore the associations between PTs' interests in pursuing each of the three extended scope practice designations and the personal/professional/attitudinal variables.</p> <p>Results</p> <p>We received 286 questionnaires (response rate = 47.7%); 258 contained usable data. The average length of time in practice was 15.4 years (SD = 10.4). About 1 in 4 PTs agreed that they were interested in assuming advanced practice roles (being a certified arthritis therapist = 28.9%, being a PT specialized in rheumatology = 23.3%, being a PT practitioner = 20.9%). Having a caseload of ≥ 40% in arthritis, having a positive attitude toward advanced practice roles in arthritis care and toward the formal credentialing process, and recognizing the difference between certification and specialisation were associated with an interest in pursing advanced practice roles.</p> <p>Conclusion</p> <p>Orthopaedic PTs in Canada indicated a fair level of interest in pursuing certification, specialisation and extended scope practice roles in arthritis care. Future research should focus on the effectiveness and cost-effectiveness of the emerging health service delivery models involving certified, specialized or extended scope practice PTs in the management of arthritis.</p

Prevention of depression and anxiety in later life: design of a randomized controlled trial for the clinical and economic evaluation of a life-review intervention

Abstract Background Depressive and anxiety symptoms in older adults could develop into significant health problems with detrimental effects on quality of life and a possibly poor prognosis. Therefore, there is a need for preventive interventions which are at once effective, acceptable and economic affordable. Methods and design This paper describes the design of a study evaluating "The stories we live by", a preventive life-review group intervention, which was recently developed for adults of 55 years and over with depressive and anxiety symptoms. Both clinical and economic effectiveness will be evaluated in a pragmatic randomized controlled trial. The participants in the intervention condition will receive the 8-session preventive intervention. The participants in the control condition will have access to usual care. Clinical end-terms are depressive and anxiety symptoms, current major depressive episode, quality of life and positive mental health post-treatment (3 months after baseline) and at follow-ups (6 and 12 months after baseline). Additional goals of this study are to identify groups for whom the intervention is particularly effective and to identify the therapeutic pathways that are vital in inducing clinical change. This will be done by analyzing if treatment response is moderated by demographics, personality, past major depressive episodes, important life events and chronically disease, and mediated by reminiscence functions, perceived control, automatic positive thoughts and meaning in life. Finally the cost-effectiveness of the intervention relative to care as usual will be assessed by computing incremental costs per case of depression and anxiety avoided (cost-effectiveness) and per quality adjusted life year (QALY) (cost utility). Discussion It is expected that both the life-review intervention and its evaluation will contribute to the existing body of knowledge in several ways. First, the intervention is unique in linking life-review with narrative therapy and in its focus on specific, positive memories. Second, the evaluation is likely to answer questions regarding the acceptability and cost-effectiveness of life-review that have not been addressed thoroughly until now. Positive results of this study will make available a new evidence-based intervention to improve public health among people of 55 years and over

Altered Development of NKT Cells, γδ T Cells, CD8 T Cells and NK Cells in a PLZF Deficient Patient

In mice, the transcription factor, PLZF, controls the development of effector functions in invariant NKT cells and a subset of NKT cell-like, γδ T cells. Here, we show that in human lymphocytes, in addition to invariant NKT cells, PLZF was also expressed in a large percentage of CD8+ and CD4+ T cells. Furthermore, PLZF was also found to be expressed in all γδ T cells and in all NK cells. Importantly, we show that in a donor lacking functional PLZF, all of these various lymphocyte populations were altered. Therefore, in contrast to mice, PLZF appears to control the development and/or function of a wide variety of human lymphocytes that represent more than 10% of the total PBMCs. Interestingly, the PLZF-expressing CD8+ T cell population was found to be expanded in the peripheral blood of patients with metastatic melanoma but was greatly diminished in patients with autoimmune disease

Polymorphisms of the TUB Gene Are Associated with Body Composition and Eating Behavior in Middle-Aged Women

BACKGROUND: The TUB gene, encoding an evolutionary conserved protein, is highly expressed in the hypothalamus and might act as a transcription factor. Mutations in TUB cause late-onset obesity, insulin-resistance and neurosensory deficits in mice. An association of common variants in the TUB gene with body weight in humans has been reported. METHODS/FINDINGS: The aim was to investigate the relationship of single nucleotide polymorphisms (SNPs) of the TUB gene (rs2272382, rs2272383 and rs1528133) with both anthropometry and self-reported macronutrient intake from a validated food frequency questionnaire. These associations were studied in a population-based, cross-sectional study of 1680 middle-aged Dutch women, using linear regression analysis. The minor allele C of the rs1528133 SNP was significantly associated with increased weight (+1.88 kg, P = 0.022) and BMI (+0.56 units, P = 0.05). Compared with non-carriers, both AG heterozygotes and AA homozygotes of the rs2272382 SNP derived less energy from fat (AG: -0.55+/-0.28%, P = 0.05, AA: -0.95+/-0.48%, P = 0.047). However, both genotypes were associated with an increased energy intake from carbohydrates (0.69+/-0.33%, P = 0.04 and 1.68+/-0.56%, P = 0.003, respectively), mainly because of a higher consumption of mono- and disaccharides. Both these SNPs, rs2272382 and rs1528133, were also associated with a higher glycemic load in the diet. The glycemic load was higher among those with AG and AA genotypes for the variant rs2272382 than among the wild types (+1.49 (95% CI: -0.27-3.24) and +3.89 (95% CI: 0.94-6.85) units, respectively). Carriers of the minor allele C of rs1528133 were associated with an increased glycemic load of 1.85 units compared with non-carriers. CONCLUSIONS: Genetic variation of the TUB gene was associated with both body composition and macronutrient intake, suggesting that TUB might influence eating behavior