Analysis of uncertainty in health care cost-effectiveness studies: an introduction to statistical issues and methods

Cost-effectiveness analysis is now an integral part of health technology assessment and addresses the question of whether a new treatment or other health care program offers good value for money. In this paper we introduce the basic framework for decision making with cost-effectiveness data and then review recent developments in statistical methods for analysis of uncertainty when cost-effectiveness estimates are based on observed data from a clinical trial. Although much research has focused on methods for calculating confidence intervals for cost-effectiveness ratios using bootstrapping or Fieller’s method, these calculations can be problematic with a ratio-based statistic where numerator and=or denominator can be zero. We advocate plotting the joint density of cost and effect differences, together with cumulative density plots known as cost-effectiveness acceptability curves (CEACs) to summarize the overall value-for-money of interventions. We also outline the net-benefit formulation of the cost-effectiveness problem and show that it has particular advantages over the standard incremental cost-effectiveness ratio formulation

Associations of Patient Health-Related Problem Solving with Disease Control, Emergency Department Visits, and Hospitalizations in HIV and Diabetes Clinic Samples

BACKGROUND: Patient problem solving and decision making are recognized as essential to effective self-management across multiple chronic diseases. However, a health-related problem-solving instrument that demonstrates sensitivity to disease control parameters in multiple diseases has not been established. OBJECTIVES: To determine, in two disease samples, internal consistency and associations with disease control of the Health Problem-Solving Scale (HPSS), a 50-item measure with 7 subscales assessing effective and ineffective problem-solving approaches, learning from past experiences, and motivation/orientation. DESIGN: Cross-sectional study. PARTICIPANTS: Outpatients from university-affiliated medical center HIV (N = 111) and diabetes mellitus (DM, N = 78) clinics. MEASUREMENTS: HPSS, CD4, hemoglobin A1c (HbA1c), and number of hospitalizations in the previous year and Emergency Department (ED) visits in the previous 6 months. RESULTS: Administration time for the HPSS ranged from 5 to 10 minutes. Cronbach’s alpha for the total HPSS was 0.86 and 0.89 for HIV and DM, respectively. Higher total scores (better problem solving) were associated with higher CD4 and fewer hospitalizations in HIV and lower HbA1c and fewer ED visits in DM. Health Problem-Solving Scale subscales representing negative problem-solving approaches were consistently associated with more hospitalizations (HIV, DM) and ED visits (DM). CONCLUSIONS: The HPSS may identify problem-solving difficulties with disease self-management and assess effectiveness of interventions targeting patient decision making in self-care

Controls on gut phosphatisation : the trilobites from the Weeks Formation Lagerstätte (Cambrian; Utah)

Despite being internal organs, digestive structures are frequently preserved in Cambrian Lagerstätten. However, the reasons for their fossilisation and their biological implications remain to be thoroughly explored. This is particularly true with arthropods--typically the most diverse fossilised organisms in Cambrian ecosystems--where digestive structures represent an as-yet underexploited alternative to appendage morphology for inferences on their biology. Here we describe the phosphatised digestive structures of three trilobite species from the Cambrian Weeks Formation Lagerstätte (Utah). Their exquisite, three-dimensional preservation reveals unique details on trilobite internal anatomy, such as the position of the mouth and the absence of a differentiated crop. In addition, the presence of paired pygidial organs of an unknown function is reported for the first time. This exceptional material enables exploration of the relationships between gut phosphatisation and the biology of organisms. Indeed, soft-tissue preservation is unusual in these fossils as it is restricted to the digestive structures, which indicates that the gut played a central role in its own phosphatisation. We hypothesize that the gut provided a microenvironment where special conditions could develop and harboured a source of phosphorus. The fact that gut phosphatization has almost exclusively been observed in arthropods could be explained by their uncommon ability to store ions (including phosphorous) in their digestive tissues. However, in some specimens from the Weeks Formation, the phosphatisation extends to the entire digestive system, suggesting that trilobites might have had some biological particularities not observed in modern arthropods. We speculate that one of them might have been an increased capacity for ion storage in the gut tissues, related to the moulting of their heavily-mineralised carapace

Pain assessment for people with dementia: a systematic review of systematic reviews of pain assessment tools.

BACKGROUND: There is evidence of under-detection and poor management of pain in patients with dementia, in both long-term and acute care. Accurate assessment of pain in people with dementia is challenging and pain assessment tools have received considerable attention over the years, with an increasing number of tools made available. Systematic reviews on the evidence of their validity and utility mostly compare different sets of tools. This review of systematic reviews analyses and summarises evidence concerning the psychometric properties and clinical utility of pain assessment tools in adults with dementia or cognitive impairment. METHODS: We searched for systematic reviews of pain assessment tools providing evidence of reliability, validity and clinical utility. Two reviewers independently assessed each review and extracted data from them, with a third reviewer mediating when consensus was not reached. Analysis of the data was carried out collaboratively. The reviews were synthesised using a narrative synthesis approach. RESULTS: We retrieved 441 potentially eligible reviews, 23 met the criteria for inclusion and 8 provided data for extraction. Each review evaluated between 8 and 13 tools, in aggregate providing evidence on a total of 28 tools. The quality of the reviews varied and the reporting often lacked sufficient methodological detail for quality assessment. The 28 tools appear to have been studied in a variety of settings and with varied types of patients. The reviews identified several methodological limitations across the original studies. The lack of a 'gold standard' significantly hinders the evaluation of tools' validity. Most importantly, the samples were small providing limited evidence for use of any of the tools across settings or populations. CONCLUSIONS: There are a considerable number of pain assessment tools available for use with the elderly cognitive impaired population. However there is limited evidence about their reliability, validity and clinical utility. On the basis of this review no one tool can be recommended given the existing evidence

Involvement of microbial mats in early fossilization by decay delay and formation of impressions and replicas of vertebrates and invertebrates

Microbial mats have been hypothesized to improve the persistence and the preservation of organic remains during fossilization processes. We test this hypothesis with long-term experiments (up to 5.5 years) using invertebrate and vertebrate corpses.Once placed on mats,the microbial community coats the corpses and forms a three-dimensional sarcophagus composed of microbial cells and exopolymeric substances (EPS). This coverage provides a template for i) moulding superficial features, resulting in negative impressions, and ii) generating replicas.The impressions of fly setulae, fish scales and frog skin verrucae are shaped mainly by small cells in an EPS matrix. Microbes also replicate delicate structures such as the three successive layers that compose a fish eye.The sarcophagus protects the body integrity, allowing the persistence of inner organs such as the ovaries and digestive apparatus in flies,the swim bladder and muscles in fish, and the bone marrow in frog legs.This study brings strong experimental evidence to the idea that mats favour metazoan fossilization by moulding, replicating and delaying decay. Rapid burial has classically been invoked as a mechanism to explain exceptional preservation. However, mats may play a similar role during early fossilization as they can preserve complex features for a long timeThis work, which is part of the research projects CGL2013-42643P and the research grant supporting M. Iniesto were funded by the Spanish Ministry of Economy and Competitiveness. The SEM facility at IMPMC was supported by Region Ile de France grant SESAME 2006 I-07-593/R, INSU-CNRS, INP-CNRS, and University Pierre et Marie Curie, Paris. SEM analyses performed for this study were supported by a grant from the Foundation Simone et Cino Del Duca (PI: K. Benzerara). Some SEM observations were also conducted at SIdI UAM (Madrid). Environmental SEM observations were performed at the MNCN (Madrid

Low back pain beliefs are associated to age, location of work, education and pain-related disability in Chinese healthcare, professionals working in China: a cross sectinal survey

Background: Low back pain (LBP) is the leading cause of disability worldwide. Evidence pointing towards a more efficacious model of care using a biopsychosocial approach for LBP management highlights the need to understand the pain-related beliefs of patients and those who treat them. The beliefs held by healthcare professionals (HCPs) are known to influence the treatment advice given to patients and consequently management outcomes. Back pain beliefs are known to be influenced by factors such as culture, education, health literacy, place of work, personal experience of LBP and the sequelae of LBP such as disability. There is currently a knowledge gap among these relationships in non-western countries. The aim of this study was to examine the associations between LBP-related beliefs among Chinese HCPs and characteristics of these HCPs. Methods: A convenience sample of 432 HCPs working in various health settings in Shanghai, China, completed a series of questionnaires assessing their demographic characteristics, LBP status, pain-related disability and their beliefs about their own LBP experience, using the Back beliefs Questionnaire (BBQ) and the Fear Avoidance Beliefs Questionnaire (FABQ).Results: Younger Chinese HCPs (20–29 years) held more negative beliefs and attitudes related to LBP compared to older HCPs (>40years; BBQ mean difference [95% CI]: 2.4 [0.9 - 3.9], p = 0.001). HCPs working outside tertiary hospitals had poorer beliefs concerning the inevitable consequences of LBP (BBQ mean difference [95% CI]: -2.4 [-3.8 - -1.0], p = 0.001). HCPs who experienced LBP had higher level of fear avoidance beliefs when experiencing high LBP-related disability (FABQ-physical mean difference [95% CI]: 2.8 [1.5 - 4.1], p < 0.001; FABQ-work mean difference [95% CI]: 6.2 [4.0 - 8.4], p < 0.001)) and had lower level of fear avoidance beliefs if they had completed postgraduate study(FABQ-physical mean difference [95% CI]: 2.9 [-5.8 - 0.0], p = 0.049).Conclusion: This study suggests that LBP-related beliefs and attitudes among Chinese HCPs are influenced by age, location of work, level of LBP-related disability and education level. Understanding back pain beliefs of Chinese HCPs forms an important foundation for future studies into the condition and its management in China

A feasibility study incorporating a pilot randomised controlled trial of oral feeding plus pre-treatment gastrostomy tube versus oral feeding plus as-needed nasogastric tube feeding in patients undergoing chemoradiation for head and neck cancer (TUBE trial): study protocol

Background There are 7000 new cases of head and neck squamous cell cancers (HNSCC) treated by the NHS each year. Stage III and IV HNSCC can be treated non-surgically by radio therapy (RT) or chemoradiation therapy (CRT). CRT can affect eating and drinking through a range of side effects with 90 % of patients undergoing this treatment requiring nutritional support via gastrostomy (G) or nasogastric (NG) tube feeding. Long-term dysphagia following CRT is a primary concern for patients. The effect of enteral feeding routes on swallowing function is not well understood, and the two feeding methods have, to date, not been compared to assess which leads to a better patient outcome. The purpose of this study is to explore the feasibility of conducting a randomised controlled trial (RCT) comparing these two options with particular emphasis on patient willingness to be randomised and clinician willingness to approach eligible patients. Methods/design This is a mixed methods multicentre study to establish the feasibility of a randomised controlled trial comparing oral feeding plus pre-treatment gastrostomy versus oral feeding plus as required nasogastric tube feeding in patients with HNSCC. A total of 60 participants will be randomised to the two arms of the study (1:1 ratio). The primary outcome of feasibility is a composite of recruitment (willingness to randomise and be randomised) and retention. A qualitative process evaluation investigating patient, family and friends and staff experiences of trial participation will also be conducted alongside an economic modelling exercise to synthesise available evidence and provide estimates of cost-effectiveness and value of information. Participants will be assessed at baseline (pre-randomisation), during CRT weekly, 3 months and 6 months. Discussion Clinicians are in equipoise over the enteral feeding options for patients being treated with CRT. Swallowing outcomes have been identified as a top priority for patients following treatment and this trial would inform a future larger scale RCT in this area to inform best practice

Biodegradative mechanism of the brown rot basidiomycete Gloeophyllum trabeum: evidence for an extracellular hydroquinone-driven fenton reaction

AbstractWe have identified key components of the extracellular oxidative system that the brown rot fungus Gloeophyllum trabeum uses to degrade a recalcitrant polymer, polyethylene glycol, via hydrogen abstraction reactions. G. trabeum produced an extracellular metabolite, 2,5-dimethoxy-1,4-benzoquinone, and reduced it to 2,5-dimethoxyhydroquinone. In the presence of 2,5-dimethoxy-1,4-benzoquinone, the fungus also reduced extracellular Fe3+ to Fe2+ and produced extracellular H2O2. Fe3+ reduction and H2O2 formation both resulted from a direct, non-enzymatic reaction between 2,5-dimethoxyhydroquinone and Fe3+. polyethylene glycol depolymerization by G. trabeum required both 2,5-dimethoxy-1,4-benzoquinone and Fe3+ and was completely inhibited by catalase. These results provide evidence that G. trabeum uses a hydroquinone-driven Fenton reaction to cleave polyethylene glycol. We propose that similar reactions account for the ability of G. trabeum to attack lignocellulose

Transmembrane helix dynamics of bacterial chemoreceptors supports a piston model of signalling.

Transmembrane α-helices play a key role in many receptors, transmitting a signal from one side to the other of the lipid bilayer membrane. Bacterial chemoreceptors are one of the best studied such systems, with a wealth of biophysical and mutational data indicating a key role for the TM2 helix in signalling. In particular, aromatic (Trp and Tyr) and basic (Arg) residues help to lock α-helices into a membrane. Mutants in TM2 of E. coli Tar and related chemoreceptors involving these residues implicate changes in helix location and/or orientation in signalling. We have investigated the detailed structural basis of this via high throughput coarse-grained molecular dynamics (CG-MD) of Tar TM2 and its mutants in lipid bilayers. We focus on the position (shift) and orientation (tilt, rotation) of TM2 relative to the bilayer and how these are perturbed in mutants relative to the wildtype. The simulations reveal a clear correlation between small (ca. 1.5 Å) shift in position of TM2 along the bilayer normal and downstream changes in signalling activity. Weaker correlations are seen with helix tilt, and little/none between signalling and helix twist. This analysis of relatively subtle changes was only possible because the high throughput simulation method allowed us to run large (n = 100) ensembles for substantial numbers of different helix sequences, amounting to ca. 2000 simulations in total. Overall, this analysis supports a swinging-piston model of transmembrane signalling by Tar and related chemoreceptors