The use of full-setting non-invasive ventilation in the home care of people with amyotrophic lateral sclerosis-motor neuron disease with end-stage respiratory muscle failure: a case series

<p>Abstract</p> <p>Introduction</p> <p>Little has been written about the use of non-invasive ventilation in the home care of amyotrophic lateral sclerosis-motor neuron disease patients with end-stage respiratory muscle failure. Nocturnal use of non-invasive ventilation has been reported to improve daytime blood gases but continuous non-invasive ventilation dependence has not been studied in this regard. There continues to be great variation by country, economics, physician interest and experience, local concepts of palliation, hospice requirements, and resources available for home care. We report a case series of home-based amyotrophic lateral sclerosis-motor neuron disease patients who refused tracheostomy and advanced non-invasive ventilation to full-setting, while maintaining normal alveolar ventilation and oxygenation in the course of the disease. Since this topic has been presented in only one center in the United States and nowhere else, it is appropriate to demonstrate that this can be done in other countries as well.</p> <p>Case presentation</p> <p>We present here the cases of three Caucasian patients (a 51-year-old Caucasian man, a 45-year-old Caucasian woman and a 57-year-old Caucasian woman) with amyotrophic lateral sclerosis who developed continuous non-invasive ventilation dependence for 15 to 27 months without major complications and were able to maintain normal CO₂and pulse oxyhemoglobin saturation despite a non-measurable vital capacity. All patients were wheelchair-dependent and receiving riluzole 50 mg twice a day. Patient one developed mild-to-moderate bulbar-innervated muscle weakness. He refused tracheostomy but accepted percutaneous gastrostomy. Patient two had two lung infections, acute bronchitis and pneumonia, which were treated with antibiotics and cough assistance at home. Patient three had three chest infections (bronchitis and pneumonias) and asthmatic episodes treated with antibiotics, bronchodilators and cough assistance at home. All patients had normal speech while receiving positive pressure; they died suddenly and with normal oxygen saturation.</p> <p>Conclusions</p> <p>Although warned that prognosis was poor as vital capacity diminished, our patients survived without invasive airway tubes and despite non-measurable vital capacity. No patient opted for tracheostomy. Our patients demonstrate the feasibility of resorting to full-setting non-invasive management to prolong survival, optimizing wellness and management at home, and the chance to die peacefully.</p

The pseudo McMillan degree of implicit transfer functions of RLC networks

We study the structure of a given RLC network without sources. Since the McMillan degree of the implicit transfer function is not a suitable measure of complexity of the network, we introduce the pseudo McMillan degree to overcome these shortcomings.Using modified nodal analysis models, which are linked directly to the natural network topology, we shaw that the pseudo-McMillan degree equals the sum of the number of capacitors and inductors minus the number of fundamental loops of capacitors and fundamental cutsets of inductors; this is the number of independent dynamic elements in the network. Exploiting this representation we derive a minimal realization of the given RLC network, that is one where the number of independent differential equations equals the pseudo McMillan degree

Selecting effective incentive structures in health care: A decision framework to support health care purchasers in finding the right incentives to drive performance

<p>Abstract</p> <p>Background</p> <p>The Ontario health care system is devolving planning and funding authority to community based organizations and moving from steering through rules and regulations to steering on performance. As part of this transformation, the Ontario Ministry of Health and Long-Term Care (MOHLTC) are interested in using incentives as a strategy to ensure alignment – that is, health service providers' goals are in accord with the goals of the health system. The objective of the study was to develop a decision framework to assist policymakers in choosing and designing effective incentive systems.</p> <p>Methods</p> <p>The first part of the study was an extensive review of the literature to identify incentives models that are used in the various health care systems and their effectiveness. The second part was the development of policy principles to ensure that the used incentive models are congruent with the values of the Ontario health care system. The principles were developed by reviewing the Ontario policy documents and through discussions with policymakers. The validation of the principles and the suggested incentive models for use in Ontario took place at two meetings. The first meeting was with experts from the research and policy community, the second with senior policymakers from the MOHLTC. Based on the outcome of those two meetings, the researchers built a decision framework for incentives. The framework was send to the participants of both meetings and four additional experts for validation.</p> <p>Results</p> <p>We identified several models that have proven, with a varying degree of evidence, to be effective in changing or enabling a health provider's performance. Overall, the literature suggests that there is no single best approach to create incentives yet and the ability of financial and non-financial incentives to achieve results depends on a number of contextual elements. After assessing the initial set of incentive models on their congruence with the four policy principles we defined nine incentive models to be appropriate for use in Ontario and potentially other health care systems that want to introduce incentives to improve performance. Subsequently, the models were incorporated in the resulting decision framework.</p> <p>Conclusion</p> <p>The design of an incentive must reflect the values and goals of the health care system, be well matched to the performance objectives and reflect a range of contextual factors that can influence the effectiveness of even well-designed incentives. As a consequence, a single policy recommendation around incentives is inappropriate. The decision framework provides health care policymakers and purchasers with a tool to support the selection of an incentive model that is the most appropriate to improve the targeted performance.</p

Optimal foraging and community structure: implications for a guild of generalist grassland herbivores

A particular linear programming model is constructed to predict the diets of each of 14 species of generalist herbivores at the National Bison Range, Montana. The herbivores have body masses ranging over seven orders of magnitude and belonging to two major taxa: insects and mammals. The linear programming model has three feeding constraints: digestive capacity, feeding time and energy requirements. A foraging strategy that maximizes daily energy intake agrees very well with the observed diets. Body size appears to be an underlying determinant of the foraging parameters leading to diet selection. Species that possess digestive capacity and feeding time constraints which approach each other in magnitude have the most generalized diets. The degree that the linear programming models change their diet predictions with a given percent change in parameter values (sensitivity) may reflect the observed ability of the species to vary their diets. In particular, the species which show the most diet variability are those whose diets tend to be balanced between monocots and dicots. The community-ecological parameters of herbivore body-size ranges and species number can possibly be related to foraging behavior.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47765/1/442_2004_Article_BF00377109.pd

The epigenetic landscape of renal cancer

This is an accepted manuscript of an article published by Nature in Nature Reviews: Nephrology on 28/11/2016, available online: https://doi.org/10.1038/nrneph.2016.168 The accepted version of the publication may differ from the final published version.The majority of kidney cancers are associated with mutations in the von Hippel-Lindau gene and a small proportion are associated with infrequent mutations in other well characterized tumour-suppressor genes. In the past 15 years, efforts to uncover other key genes involved in renal cancer have identified many genes that are dysregulated or silenced via epigenetic mechanisms, mainly through methylation of promoter CpG islands or dysregulation of specific microRNAs. In addition, the advent of next-generation sequencing has led to the identification of several novel genes that are mutated in renal cancer, such as PBRM1, BAP1 and SETD2, which are all involved in histone modification and nucleosome and chromatin remodelling. In this Review, we discuss how altered DNA methylation, microRNA dysregulation and mutations in histone-modifying enzymes disrupt cellular pathways in renal cancers

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified