Mixed methods evaluation of a hospital group model using an embedded research approach: study protocol

INTRODUCTION: Hospital group models represent an organisational form that aims to bring together multiple provider organisations with a central headquarters and unified leadership responsible for locally managed operating units, standardised systems and a value-set shared across the group. These models seek to improve outcomes by reducing unwarranted variations in care provision and reducing costs through economies of scale. There is limited evidence on the impact and processes of implementing these models, so this study aims to evaluate one case study of a hospital group model. METHODS AND ANALYSIS: We will conduct a formative, mixed-methods evaluation using an embedded research approach to analyse the implementation of the model and its impact on outcomes and costs. We will carry out a multisited ethnography to analyse the programme theory for model design and implementation, the barriers and facilitators in the implementation; and wider contextual issues that influence implementation using semi-structured interviews (n=80), non-participant observations (n=80 hours), 'shadowing' (n=20 hours) and documentary analysis. We will also carry out an economic evaluation composed of a cost-consequence analysis and a return on investment analysis to evaluate the costs of creating and running the model and balance these against the potential cost-savings. ETHICS AND DISSEMINATION: The study protocol was reviewed by the local R&D Office and University College London Ethics Committee and classified as a service evaluation, not requiring approval by a research ethics committee. We will follow guidelines for informed consent, confidentiality and information governance, and address issues of critical distance prevalent in embedded research. Findings will be shared at regular time points to inform the implementation of the model. The evaluation will also generate: an evaluation framework to evaluate future changes; recommendations for meaningful baseline data and measuring improvement; identification of implementation costs and potential cost-savings; and lessons for the National Health Service on implementing these models

Extensive cross-disciplinary analysis of biological and chemical control of Calanus finmarchicus reproduction during an aldehyde forming diatom bloom in mesocosms

Egg and faecal pellet production and egg hatching success of the calanoid copepod Calanus finmarchicus were monitored over a period of 14 days (14-28 April, 2008) while fed water from 4 differently treated mesocosms and ambient water. Two of the mesocosms used were inoculated with the polyunsaturated aldehyde (PUA)-producing diatom Skeletonema marinoi, while 2 received only nutrient additions with or without silica. The mesocosms developed blooms of S. marinoi, mixed diatoms or the haptophyte Phaeocystis pouchetii, respectively. Faecal pellet production of C. finmarchicus increased with increasing food availability. Egg production increased with time in all mesocosms to a maximum single female production of 232 eggs female(-1) day(-1) (average of 90 eggs female(-1) day(-1)) and followed the development of ciliates and P. pouchetii, but was not affected by the observed high (up to 15 nmol L(-1)) PUA production potential of the phytoplankton. The hatching success of the eggs produced on the mesocosm diets was high (78-96%) and was not affected by either aldehydes in the maternal diet or exposure to the dissolved aldehydes in the water

International Veterinary Epilepsy Task Force consensus proposal: Medical treatment of canine epilepsy in Europe

In Europe, the number of antiepileptic drugs (AEDs) licensed for dogs has grown considerably over the last years. Nevertheless, the same questions remain, which include, 1) when to start treatment, 2) which drug is best used initially, 3) which adjunctive AED can be advised if treatment with the initial drug is unsatisfactory, and 4) when treatment changes should be considered. In this consensus proposal, an overview is given on the aim of AED treatment, when to start long-term treatment in canine epilepsy and which veterinary AEDs are currently in use for dogs. The consensus proposal for drug treatment protocols, 1) is based on current published evidence-based literature, 2) considers the current legal framework of the cascade regulation for the prescription of veterinary drugs in Europe, and 3) reflects the authors’ experience. With this paper it is aimed to provide a consensus for the management of canine idiopathic epilepsy. Furthermore, for the management of structural epilepsy AEDs are inevitable in addition to treating the underlying cause, if possible

Socioeconomic Predictors of Cognition in Ugandan Children: Implications for Community Interventions

Background: Several interventions to improve cognition in at risk children have been suggested. Identification of key variables predicting cognition is necessary to guide these interventions. This study was conducted to identify these variables in Ugandan children and guide such interventions. Methods: A cohort of 89 healthy children (45 females) aged 5 to 12 years old were followed over 24 months and had cognitive tests measuring visual spatial processing, memory, attention and spatial learning administered at baseline, 6 months and 24 months. Nutritional status, child’s educational level, maternal education, socioeconomic status and quality of the home environment were also measured at baseline. A multivariate, longitudinal model was then used to identify predictors of cognition over the 24 months. Results: A higher child’s education level was associated with better memory (p = 0.03), attention (p = 0.005) and spatial learning scores over the 24 months (p = 0.05); higher nutrition scores predicted better visual spatial processing (p = 0.002) and spatial learning scores (p = 0.008); and a higher home environment score predicted a better memory score (p = 0.03). Conclusion: Cognition in Ugandan children is predicted by child’s education, nutritional status and the home environment

6-OHDA-induced dopaminergic neurodegeneration in <i>Caenorhabditis elegans</i> is promoted by the engulfment pathway and inhibited by the transthyretin-related protein TTR-33

<div><p>Oxidative stress is linked to many pathological conditions including the loss of dopaminergic neurons in Parkinson’s disease. The vast majority of disease cases appear to be caused by a combination of genetic mutations and environmental factors. We screened for genes protecting <i>Caenorhabditis elegans</i> dopaminergic neurons from oxidative stress induced by the neurotoxin 6-hydroxydopamine (6-OHDA) and identified the <u>t</u>rans<u>t</u>hyretin-<u>r</u>elated gene <i>ttr-33</i>. The only described <i>C</i>. <i>elegans</i> transthyretin-related protein to date, TTR-52, has been shown to mediate corpse engulfment as well as axon repair. We demonstrate that TTR-52 and TTR-33 have distinct roles. TTR-33 is likely produced in the posterior arcade cells in the head of <i>C</i>. <i>elegans</i> larvae and is predicted to be a secreted protein. TTR-33 protects <i>C</i>. <i>elegans</i> from oxidative stress induced by paraquat or H₂O₂ at an organismal level. The increased oxidative stress sensitivity of <i>ttr-33</i> mutants is alleviated by mutations affecting the KGB-1 MAPK kinase pathway, whereas it is enhanced by mutation of the JNK-1 MAPK kinase. Finally, we provide genetic evidence that the <i>C</i>. <i>elegans</i> cell corpse engulfment pathway is required for the degeneration of dopaminergic neurons after exposure to 6-OHDA. In summary, we describe a new neuroprotective mechanism and demonstrate that TTR-33 normally functions to protect dopaminergic neurons from oxidative stress-induced degeneration, potentially by acting as a secreted sensor or scavenger of oxidative stress.</p></div

Determinants of intra-household food allocation between adults in South Asia - a systematic review.

BACKGROUND: Nutrition interventions, often delivered at the household level, could increase their efficiency by channelling resources towards pregnant or lactating women, instead of leaving resources to be disproportionately allocated to traditionally favoured men. However, understanding of how to design targeted nutrition programs is limited by a lack of understanding of the factors affecting the intra-household allocation of food. METHODS: We systematically reviewed literature on the factors affecting the allocation of food to adults in South Asian households (in Afghanistan, Bangladesh, Bhutan, India, Islamic Republic of Iran, Maldives, Nepal, Pakistan, Sri Lanka) and developed a framework of food allocation determinants. Two reviewers independently searched and filtered results from PubMed, Web of Knowledge and Scopus databases by using pre-defined search terms and hand-searching the references from selected papers. Determinants were extracted, categorised into a framework, and narratively described. We used adapted Downs and Black and Critical Appraisal Skills Programme checklists to assess the quality of evidence. RESULTS: Out of 6928 retrieved studies we found 60 relevant results. Recent, high quality evidence was limited and mainly from Bangladesh, India and Nepal. There were no results from Iran, Afghanistan, Maldives, or Bhutan. At the intra-household level, food allocation was determined by relative differences in household members' income, bargaining power, food behaviours, social status, tastes and preferences, and interpersonal relationships. Household-level determinants included wealth, food security, occupation, land ownership, household size, religion / ethnicity / caste, education, and nutrition knowledge. In general, the highest inequity occurred in households experiencing severe or unexpected food insecurity, and also in better-off, high caste households, whereas poorer, low caste but not severely food insecure households were more equitable. Food allocation also varied regionally and seasonally. CONCLUSION: Program benefits may be differentially distributed within households of different socioeconomic status, and targeting of nutrition programs might be improved by influencing determinants that are amenable to change, such as food security, women's employment, or nutrition knowledge. Longitudinal studies in different settings could unravel causal effects. Conclusions are not generalizable to the whole South Asian region, and research is needed in many countries

Drivers of population structure of the bottlenose dolphin (Tursiops truncatus) in the Eastern Mediterranean Sea

The drivers of population differentiation in oceanic high dispersal organisms, have been crucial for research in evolutionary biology. Adaptation to different environments is commonly invoked as a driver of differentiation in the oceans, in alternative to geographic isolation. In this study, we investigate the population structure and phylogeography of the bottlenose dolphin (Tursiops truncatus) in the Mediterranean Sea, using microsatellite loci and the entire mtDNA control region. By further comparing the Mediterranean populations with the well described Atlantic populations, we addressed the following hypotheses: (1) bottlenose dolphins show population structure within the environmentally complex Eastern Mediterranean Sea; (2) population structure was gained locally or otherwise results from chance distribution of preexisting genetic structure; (3) strong demographic variations within the Mediterranean basin have affected genetic variation sufficiently to bias detected patterns of population structure. Our results suggest that bottlenose dolphin exhibits population structures that correspond well to the main Mediterranean oceanographic basins. Furthermore, we found evidence for fine scale population division within the Adriatic and the Levantine seas. We further describe for the first time, a distinction between populations inhabiting pelagic and coastal regions within the Mediterranean. Phylogeographic analysis suggests that current genetic structure, results mostly from stochastic distribution of Atlantic genetic variation, during a recent postglacial expansion. Comparison with Atlantic mtDNA haplotypes, further suggest the existence of a metapopulation across North Atlantic/Mediterranean, with pelagic regions acting as source for coastal environments

The FiCTION dental trial protocol - fillings children's teeth: indicated or not?

Background: There is a lack of evidence for effective management of dental caries (decay) in children’s primary (baby) teeth and an apparent failure of conventional dental restorations (fillings) to prevent dental pain and infection for UK children in Primary Care. UK dental schools’ teaching has been based on British Society of Paediatric Dentistry guidance which recommends that caries in primary teeth should be removed and a restoration placed. However, the evidence base for this is limited in volume and quality, and comes from studies conducted in either secondary care or specialist practices. Restorations provided in specialist environments can be effective but the generalisability of this evidence to Primary Care has been questioned. The FiCTION trial addresses the Health Technology Assessment (HTA) Programme’s commissioning brief and research question “What is the clinical and cost effectiveness of restoration caries in primary teeth, compared to no treatment?” It compares conventional restorations with an intermediate treatment strategy based on the biological (sealing-in) management of caries and with no restorations. Methods/Design: This is a Primary Care-based multi-centre, three-arm, parallel group, patient-randomised controlled trial. Practitioners are recruiting 1461 children, (3–7 years) with at least one primary molar tooth where caries extends into dentine. Children are randomized and treated according to one of three treatment approaches; conventional caries management with best practice prevention, biological management of caries with best practice prevention or best practice prevention alone. Baseline measures and outcome data (at review/treatment during three year follow-up) are assessed through direct reporting, clinical examination including blinded radiograph assessment, and child/parent questionnaires. The primary outcome measure is the incidence of either pain or infection related to dental caries. Secondary outcomes are; incidence of caries in primary and permanent teeth, patient quality of life, cost-effectiveness, acceptability of treatment strategies to patients and parents and their experiences, and dentists’ preferences. Discussion: FiCTION will provide evidence for the most clinically-effective and cost-effective approach to managing caries in children’s primary teeth in Primary Care. This will support general dental practitioners in treatment decision making for child patients to minimize pain and infection in primary teeth. The trial is currently recruiting patients

Molecular marks for epigenetic identification of developmental and cancer stem cells

Epigenetic regulations of genes by reversible methylation of DNA (at the carbon-5 of cytosine) and numerous reversible modifications of histones play important roles in normal physiology and development, and epigenetic deregulations are associated with developmental disorders and various disease states, including cancer. Stem cells have the capacity to self-renew indefinitely. Similar to stem cells, some malignant cells have the capacity to divide indefinitely and are referred to as cancer stem cells. In recent times, direct correlation between epigenetic modifications and reprogramming of stem cell and cancer stem cell is emerging. Major discoveries were made with investigations on reprogramming gene products, also known as master regulators of totipotency and inducer of pluoripotency, namely, OCT4, NANOG, cMYC, SOX2, Klf4, and LIN28. The challenge to induce pluripotency is the insertion of four reprogramming genes (Oct4, Sox2, Klf4, and c-Myc) into the genome. There are always risks of silencing of these genes by epigenetic modifications in the host cells, particularly, when introduced through retroviral techniques. In this contribution, we will discuss some of the major discoveries on epigenetic modifications within the chromatin of various genes associated with cancer progression and cancer stem cells in comparison to normal development of stem cell. These modifications may be considered as molecular signatures for predicting disorders of development and for identifying disease states