Exploring the impact of the COVID-19 pandemic and UK lockdown on individuals with experience of eating disorders

Background The coronavirus disease 2019 (COVID-19) pandemic may raise unique challenges for individuals with experience of eating disorders. Many factors have potential for detrimental impacts on psychological wellbeing and eating disorder recovery, including: Disruption to living situations, ‘social distancing’ restrictions, difficult access to healthcare, and societal changes to food behaviours and technology usage. To date, little is known on the impact of the pandemic on this population, particularly within the UK. Method A mixed-methods online survey was developed for the purpose of this study. Data was collected from 129 individuals currently experiencing, or in recovery from, an eating disorder during the early stages of the UK pandemic lockdown. Participants were aged between 16 and 65 years, with 121 participants identifying as female, 7 male and 1 participant preferring not to disclose their gender. Results Findings suggest that the pandemic is having a profound, negative impact upon individuals with experience of eating disorders. Eight key themes were generated: Disruption to living situation, increased social isolation and reduced access to usual support networks, changes to physical activity rates, reduced access to healthcare services, disruption to routine and perceived control, changes to relationship with food, increased exposure to triggering messages, and positive outcomes. The results suggest detrimental impacts on psychological wellbeing including decreased feelings of control, increased feelings of social isolation, increased rumination about disordered eating, and low feelings of social support. Conclusions Individuals with eating disorders are at significant risk of negative impacts of the pandemic. There is a vital need for interventions to support this population. Inequalities in healthcare provision were identified, emphasising a need for a more cohesive approach to remote treatment across UK healthcare services. Positive aspects of technology use were identified but the results suggest a need to address and/or limit the potential for negative impacts of public messages around food and exercise behaviours, and to co-design technologies with end-users to facilitate effective treatment

The role of TcdB and TccC subunits in secretion of the photorhabdus Tcd toxin complex

The Toxin Complex (TC) is a large multi-subunit toxin encoded by a range of bacterial pathogens. The best-characterized examples are from the insect pathogens Photorhabdus, Xenorhabdus and Yersinia. They consist of three large protein subunits, designated A, B and C that assemble in a 5:1:1 stoichiometry. Oral toxicity to a range of insects means that some have the potential to be developed as pest control technology. The three subunit proteins do not encode any recognisable export sequences and as such little progress has been made in understanding their secretion. We have developed heterologous TC production and secretion models in E. coli and used them to ascribe functions to different domains of the crucial B+C sub-complex. We have determined that the B and C subunits use a secretion mechanism that is either encoded by the proteins themselves or employ an as yet undefined system common to laboratory strains of E. coli. We demonstrate that both the N-terminal domains of the B and C subunits are required for secretion of the whole complex. We propose a model whereby the N-terminus of the C-subunit toxin exports the B+C sub-complex across the inner membrane while that of the B-subunit allows passage across the outer membrane. We also demonstrate that even in the absence of the B-subunit, that the C-subunit can also facilitate secretion of the larger A-subunit. The recognition of this novel export system is likely to be of importance to future protein secretion studies. Finally, the identification of homologues of B and C subunits in diverse bacterial pathogens, including Burkholderia and Pseudomonas, suggests that these toxins are likely to be important in a range of different hosts, including man

Cost effectiveness of total knee arthroplasty from a health care providers' perspective before and after introduction of an interdisciplinary clinical pathway - is investment always improvement?

<p>Abstract</p> <p>Background</p> <p>Total knee arthroplasty (TKA) is an effective, but also cost-intensive health care intervention for end stage osteoarthritis. This investigation was designed to evaluate the cost-effectiveness of TKA before versus after introduction of an interdisciplinary clinical pathway from a University Orthopedic Surgery Department's cost perspective as an interdisciplinary full service health care provider.</p> <p>Methods</p> <p>A prospective trial recruited two sequential cohorts of 132 and 128 consecutive patients, who were interviewed by means of the WOMAC questionnaire. Direct process costs from the health care providers' perspective were estimated according to the German DRG calculation framework. The health economic evaluation was based on margiual cost-effectveness ratios (MCERs); an individual marginal cost effectiveness relation ≤ 100 € per % WOMAC index increase was considered as primary endpoint of the confirmatory cohort comparison. The interdisciplinary clinical pathway under consideration primarily consisted of a voluntary preoperative personal briefing of patients concerning postoperatively expectable progess in health status and optimum use of walking aids after surgery. All patients were supplied with written information on these topics, attendance of the personal briefing also included preoperative training for postoperative mobilisation by the Department's physiotherapeutic staff.</p> <p>Results</p> <p>An individual marginal cost effectiveness relation ≤ 100 €/% WOMAC index increase was found in 38% of the patients in the pre pathway implementation cohort versus in 30% of the post pathway implementation cohort (Fisher p = 0.278). Both cohorts showed substantial improvement in WOMAC scores (39 versus 35% in median), whereas the cohort did not differ significantly in the median WOMAC score before surgery (41% for the pre pathway cohort versus 44% for the post pathway cohort). Despite a locally significant decrease in costs (4303 versus 4194 € in median), the individual cost/benefit relation became worse after introduction of the pathway: for the first cohort the MCER was estimated 108 € per gained % WOMAC index increase (86 - 150 €/%) versus 118 €/% WOMAC gain (93 - 173 €/%) in the second cohort after pathway implementation. In summary, the proposed critical pathway for TKA could be shown to be significantly cost efficient, but not cost effective concerning functional outcome, when the above individual marginal cost effectiveness criterion was concentrated on.</p> <p>Conclusions</p> <p>The introduction of an interdisciplinary clinical pathway does not necessarily improve patient related outcomes. On the contrary, cost effectiveness from the health care providers' perspective may even turn out remarkably reduced in the setting considered here (functional outcome assessment after treatment by a full service health care provider).</p

An initial application of computerized adaptive testing (CAT) for measuring disability in patients with low back pain

<p>Abstract</p> <p>Background</p> <p>Recent approaches to outcome measurement involving Computerized Adaptive Testing (CAT) offer an approach for measuring disability in low back pain (LBP) in a way that can reduce the burden upon patient and professional. The aim of this study was to explore the potential of CAT in LBP for measuring disability as defined in the International Classification of Functioning, Disability and Health (ICF) which includes impairments, activity limitation, and participation restriction.</p> <p>Methods</p> <p>266 patients with low back pain answered questions from a range of widely used questionnaires. An exploratory factor analysis (EFA) was used to identify disability dimensions which were then subjected to Rasch analysis. Reliability was tested by internal consistency and person separation index (PSI). Discriminant validity of disability levels were evaluated by Spearman correlation coefficient (r), intraclass correlation coefficient [ICC(2,1)] and the Bland-Altman approach. A CAT was developed for each dimension, and the results checked against simulated and real applications from a further 133 patients.</p> <p>Results</p> <p>Factor analytic techniques identified two dimensions named "body functions" and "activity-participation". After deletion of some items for failure to fit the Rasch model, the remaining items were mostly free of Differential Item Functioning (DIF) for age and gender. Reliability exceeded 0.90 for both dimensions. The disability levels generated using all items and those obtained from the real CAT application were highly correlated (i.e. > 0.97 for both dimensions). On average, 19 and 14 items were needed to estimate the precise disability levels using the initial CAT for the first and second dimension. However, a marginal increase in the standard error of the estimate across successive iterations substantially reduced the number of items required to make an estimate.</p> <p>Conclusion</p> <p>Using a combination approach of EFA and Rasch analysis this study has shown that it is possible to calibrate items onto a single metric in a way that can be used to provide the basis of a CAT application. Thus there is an opportunity to obtain a wide variety of information to evaluate the biopsychosocial model in its more complex forms, without necessarily increasing the burden of information collection for patients.</p

Measuring patient-reported outcomes: moving beyond misplaced common sense to hard science

Interest in the patient's views of his or her illness and treatment has increased dramatically. However, our ability to appropriately measure such issues lags far behind the level of interest and need. Too often such measurement is considered to be a simple and trivial activity that merely requires the application of common sense. However, good quality measurement of patient-reported outcomes is a complex activity requiring considerable expertise and experience. This review considers the most important issues related to such measurement in the context of chronic disease and details how instruments should be developed, validated and adapted for use in additional languages. While there is often consensus on how best to undertake these activities, there is generally little evidence to support such accord. The present article questions these orthodox views and suggests alternative approaches that have been shown to be effective

Ultra-Fast and Sensitive Detection of Non-Typhoidal Salmonella Using Microwave-Accelerated Metal-Enhanced Fluorescence (“MAMEF”)

Certain serovars of Salmonella enterica subsp. enterica cause invasive disease (e.g., enteric fever, bacteremia, septicemia, meningitis, etc.) in humans and constitute a global public health problem. A rapid, sensitive diagnostic test is needed to allow prompt initiation of therapy in individual patients and for measuring disease burden at the population level. An innovative and promising new rapid diagnostic technique is microwave-accelerated metal-enhanced fluorescence (MAMEF). We have adapted this assay platform to detect the chromosomal oriC locus common to all Salmonella enterica subsp. enterica serovars. We have shown efficient lysis of biologically relevant concentrations of Salmonella spp. suspended in bacteriological media using microwave-induced lysis. Following lysis and DNA release, as little as 1 CFU of Salmonella in 1 ml of medium can be detected in <30 seconds. Furthermore the assay is sensitive and specific: it can detect oriC from Salmonella serovars Typhi, Paratyphi A, Paratyphi B, Paratyphi C, Typhimurium, Enteritidis and Choleraesuis but does not detect Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Streptococcus pneumoniae, Haemophilus influenzae or Acinetobacter baumanii. We have also performed preliminary experiments using a synthetic Salmonella oriC oligonucleotide suspended in whole human blood and observed rapid detection when the sample was diluted 1∶1 with PBS. These pre-clinical data encourage progress to the next step to detect Salmonella in blood (and other ordinarily sterile, clinically relevant body fluids)

Extraction and sensitive detection of toxins A and B from the human pathogen Clostridium difficile in 40 seconds using microwave-accelerated metal-enhanced fluorescence.

Clostridium difficile is the primary cause of antibiotic associated diarrhea in humans and is a significant cause of morbidity and mortality. Thus the rapid and accurate identification of this pathogen in clinical samples, such as feces, is a key step in reducing the devastating impact of this disease. The bacterium produces two toxins, A and B, which are thought to be responsible for the majority of the pathology associated with the disease, although the relative contribution of each is currently a subject of debate. For this reason we have developed a rapid detection assay based on microwave-accelerated metal-enhanced fluorescence which is capable of detecting the presence of 10 bacteria in unprocessed human feces within 40 seconds. These promising results suggest that this prototype biosensor has the potential to be developed into a rapid, point of care, real time diagnostic assay for C. difficile

Underwriting Apophenia and Cryptids: Are Cycles Statistical Figments of our Imagination?

This paper re-examines the evidence in favour of the existence of underwriting cycles in property and casualty insurance and their economical significance. Using a meta-analysis of published papers in the area of insurance economics, we show that the evidence supporting the existence of underwriting cycles is misleading. There is, in fact, little evidence in favour of insurance cycles with a linear autoregressive character. This means that any cyclicality in firm profitability in the property and casualty insurance industry is not predictable in a classical econometric framework. It follows that pricing in the property and casualty insurance industry is not incompatible with that of a competitive market

Shotgun sequencing of Yersinia enterocolitica strain W22703 (biotype 2, serotype O:9): genomic evidence for oscillation between invertebrates and mammals

<p>Abstract</p> <p>Background</p> <p><it>Yersinia enterocolitica </it>strains responsible for mild gastroenteritis in humans are very diverse with respect to their metabolic and virulence properties. Strain W22703 (biotype 2, serotype O:9) was recently identified to possess nematocidal and insecticidal activity. To better understand the relationship between pathogenicity towards insects and humans, we compared the W22703 genome with that of the highly pathogenic strain 8081 (biotype1B; serotype O:8), the only <it>Y. enterocolitica </it>strain sequenced so far.</p> <p>Results</p> <p>We used whole-genome shotgun data to assemble, annotate and analyse the sequence of strain W22703. Numerous factors assumed to contribute to enteric survival and pathogenesis, among them osmoregulated periplasmic glucan, hydrogenases, cobalamin-dependent pathways, iron uptake systems and the <it>Yersinia </it>genome island 1 (YGI-1) involved in tight adherence were identified to be common to the 8081 and W22703 genomes. However, sets of ~550 genes revealed to be specific for each of them in comparison to the other strain. The plasticity zone (PZ) of 142 kb in the W22703 genome carries an ancient flagellar cluster Flg-2 of ~40 kb, but it lacks the pathogenicity island YAPI_Ye, the secretion system <it>ysa </it>and <it>yts1</it>, and other virulence determinants of the 8081 PZ. Its composition underlines the prominent variability of this genome region and demonstrates its contribution to the higher pathogenicity of biotype 1B strains with respect to W22703. A novel type three secretion system of mosaic structure was found in the genome of W22703 that is absent in the sequenced strains of the human pathogenic <it>Yersinia </it>species, but conserved in the genomes of the apathogenic species. We identified several regions of differences in W22703 that mainly code for transporters, regulators, metabolic pathways, and defence factors.</p> <p>Conclusion</p> <p>The W22703 sequence analysis revealed a genome composition distinct from other pathogenic <it>Yersinia enterocolitica </it>strains, thus contributing novel data to the <it>Y. enterocolitica </it>pan-genome. This study also sheds further light on the strategies of this pathogen to cope with its environments.</p

Pdl1 Is a Putative Lipase that Enhances Photorhabdus Toxin Complex Secretion

The Toxin Complex (TC) is a large multi-subunit toxin first characterized in the insect pathogens Photorhabdus and Xenorhabdus, but now seen in a range of pathogens, including those of humans. These complexes comprise three protein subunits, A, B and C which in the Xenorhabdus toxin are found in a 4∶1∶1 stoichiometry. Some TCs have been demonstrated to exhibit oral toxicity to insects and have the potential to be developed as a pest control technology. The lack of recognisable signal sequences in the three large component proteins hinders an understanding of their mode of secretion. Nevertheless, we have shown the Photorhabdus luminescens (Pl) Tcd complex has been shown to associate with the bacteria's surface, although some strains can also release it into the surrounding milieu. The large number of tc gene homologues in Pl make study of the export process difficult and as such we have developed and validated a heterologous Escherichia coli expression model to study the release of these important toxins. In addition to this model, we have used comparative genomics between a strain that releases high levels of Tcd into the supernatant and one that retains the toxin on its surface, to identify a protein responsible for enhancing secretion and release of these toxins. This protein is a putative lipase (Pdl1) which is regulated by a small tightly linked antagonist protein (Orf53). The identification of homologues of these in other bacteria, linked to other virulence factor operons, such as type VI secretion systems, suggests that these genes represent a general and widespread mechanism for enhancing toxin release in Gram negative pathogens