Communities as ‘renewable energy’ for health care services? A multi-methods study into the form, scale, and role of voluntary support for community hospitals in England

Objective To examine the forms, scale and role of community and voluntary support for community hospitals in England. Design A multi-methods study. Quantitative analysis of Charity Commission data on levels of volunteering and voluntary income for charities supporting community hospitals. Nine qualitative case studies of community hospitals and their surrounding communities, including interviews and focus groups. Setting Community hospitals in England and their surrounding communities. Participants Charity Commission data for 245 community hospital Leagues of Friends. Interviews with staff (89), patients (60), carers (28), volunteers (35), community representatives (20), managers and commissioners (9). Focus groups with multi-disciplinary teams (8 groups across nine sites, involving 43 respondents), volunteers (6 groups, 33 respondents) and community stakeholders (8 groups, 54 respondents). Results Communities support community hospitals through: human resources (average = 24 volunteers a year per hospital); financial resources (median voluntary income = £15,632); practical resources through services and activities provided by voluntary and community groups; and intellectual resources (e.g. consultation and coproduction). Communities provide valuable supplementary resources to the NHS, enhancing community hospital services, patient experience, staff morale and volunteer well-being. Such resources, however, vary in level and form from hospital to hospital and over time: voluntary income is on the decline, as is membership of League of Friends, and it can be hard to recruit regular, active volunteers. Conclusions Communities can be a significant resource for health care services, in ways which can enhance patient experience and service quality. Harnessing that resource, however, is not straight forward and there is a perception that it might be becoming more difficult questioning the extent to which it can be considered sustainable or ‘renewable’

Multispectral tissue mapping: developing a concept for the optical evaluation of liver disease

Purpose: Alterations in the optical absorption behavior of liver tissue secondary to pathological processes can be evaluated by multispectral analysis, which is increasingly being explored as an imaging adjunct for use in liver surgery. Current methods are either invasive or have a limited wavelength spectrum, which restricts utility. This proof of concept study describes the development of a multispectral imaging (MSI) method called multispectral tissue mapping (MTM) that addresses these issues. Approach: The imaging system consists of a tunable excitation light source and a near-infrared camera. Following the development stage, proof of concept experiments are carried out where absorption spectra from colorectal cancer liver metastasis (CRLM), hepatocellular carcinoma (HCC), and liver steatosis specimen are acquired and compared to controls. Absorption spectra are compared to histopathology examination as the current gold standard for tissue assessment. Generalized linear mixed modeling is employed to compare absorption characteristics of individual pixels and to select wavelengths for false color image processing with the aim of visually enhancing cancer tissue. Results: Analysis of individual pixels revealed distinct absorption spectra therefore suggesting that MTM is possible. A prominent absorption peak at 1210 nm was found in lipid-rich animal tissues and steatotic liver specimen. Liver cancer tissue had a heterogeneous appearance on MSI. Subsequent statistical analysis suggests that measuring changes in absorption behavior may be a feasible method to estimate the pixel-based probability of cancer being present. In CRLM, this was observed throughout 1100 to 1700 nm, whereas in HCC it was concentrated around 1140 and 1430 nm. False color image processing visibly enhances contrast between cancer and normal liver tissues. Conclusions: The system’s ability to enable no-touch MSI at 1100 to 1700 nm was demonstrated. Preliminary data suggest that MTM warrants further exploration as a potential imaging tool for the detection of liver cancer during surger

Identification of liver metastases with probe-based confocal laser endomicroscopy at two excitation wavelengths.

BACKGROUND: Metastasis of colorectal cancer to the liver is the most common indication for hepatic resection in a western population. Incomplete excision of malignancy due to residual microscopic disease normally results in worse patient outcome. Therefore, a method aiding in the real time discrimination of normal and malignant tissue on a microscopic level would be of benefit. MATERIAL AND METHODS: The ability of fluorescent probe-based confocal laser endomicroscopy (pCLE) to identify normal and malignant liver tissue was evaluated in an orthotopic murine model of colorectal cancer liver metastasis (CRLM). To maximise information yield, two clinical fluorophores, fluorescein and indocyanine green (ICG) were injected and imaged in a dual wavelength approach (488 and 660 nm, respectively). Visual tissue characteristics on pCLE examination were compared with histological features. Fluorescence intensity in both tissues was statistically analysed to elucidate if this can be used to differentiate between normal and malignant tissue. RESULTS: Fluorescein (488 nm) enabled good visualisation of normal and CRLM tissue, whereas ICG (660 nm) visualisation was limited to normal liver tissue only. Fluorescence intensity in areas of CRLM was typically 53-100% lower than normal hepatic parenchyma. Using general linear mixed modelling and receiver operating characteristic analysis, high fluorescence intensity was found to be statistically more likely in normal hepatic tissue. CONCLUSION: Real time discrimination between normal liver parenchyma and metastatic tissue with pCLE examination of fluorescein and ICG is feasible. Employing two (rather than a single) fluorophores allows a combination of qualitative and quantitative characteristics to be used to distinguish between hepatic parenchyma and CRLM. Lasers Surg. Med. © 2016 Wiley Periodicals, Inc

Genotype-Phenotype Correlation for TGFBI Corneal Dystrophies Identifies p.(G623D) as a Novel Cause of Epithelial Basement Membrane Dystrophy.

Purpose: The majority of anterior corneal dystrophies are caused by dominant mutations in TGFBI (transforming growth factor β-induced) collectively known as the epithelial-stromal TGFBI dystrophies. Most cases of epithelial basement membrane dystrophy (EBMD) are thought to result from a degenerative (nongenetic) process; however, a minority of cases are associated with specific TGFBI mutations. We evaluated the spectrum of TGFBI mutations and associated phenotypes in a United Kingdom cohort with typical epithelial-stromal TGFBI dystrophies and an EBMD cohort. Methods: We recruited 68 probands with a clinical diagnosis of epithelial-stromal TGFBI dystrophy and 23 probands with bilateral EBMD. DNA was extracted from peripheral leukocytes, and TGFBI was bi-directly Sanger sequenced. Results: Nine TGFBI mutations were identified. The most common occurred at the mutation hot-spot residues R124 and R555 in 61 probands; these individuals had a genotype-phenotype correlation consistent with prior reports. Four probands with lattice corneal dystrophy carried a mutation in exon 14: p.(A620D), p.(V625D), and p.(H626R). We identified a p.(G623D) mutation in five probands, including two probands from the EBMD cohort. These subjects typically had an onset of severe recurrent corneal epithelial erosion in the fourth decade with mild diffuse or geographic subepithelial corneal opacities and only small anterior stromal lattice structures in older individuals. Symptoms of painful epithelial erosion improved markedly following phototherapeutic keratectomy. Conclusions: There was a strong correlation between genotype and phenotype for the majority of TGFBI mutations. In this cohort, the p.(G623D) mutation caused a greater proportion of TGFBI-associated disease than anticipated, associated with variable phenotypes including individuals diagnosed with EBMD

Non-Penetrance for Ocular Phenotype in Two Individuals Carrying Heterozygous Loss-of-Function ZEB1 Alleles

ZEB1 loss-of-function (LoF) alleles are known to cause a rare autosomal dominant disorder—posterior polymorphous corneal dystrophy type 3 (PPCD3). To date, 50 pathogenic LoF variants have been identified as disease-causing and familial studies have indicated that the PPCD3 phenotype is penetrant in approximately 95% of carriers. In this study, we interrogated in-house exomes (n = 3616) and genomes (n = 88) for the presence of putative heterozygous LoF variants in ZEB1. Next, we performed detailed phenotyping in a father and his son who carried a novel LoF c.1279C>T; p.(Glu427*) variant in ZEB1 (NM_030751.6) absent from the gnomAD v.2.1.1 dataset. Ocular examination of the two subjects did not show any abnormalities characteristic of PPCD3. GnomAD (n = 141,456 subjects) was also interrogated for LoF ZEB1 variants, notably 8 distinct heterozygous changes presumed to lead to ZEB1 haploinsufficiency, not reported to be associated with PPCD3, have been identified. The NM_030751.6 transcript has a pLI score ≥ 0.99, indicating extreme intolerance to haploinsufficiency. In conclusion, ZEB1 LoF variants are present in a general population at an extremely low frequency. As PPCD3 can be asymptomatic, the true penetrance of ZEB1 LoF variants remains currently unknown but is likely to be lower than estimated by the familial led approaches adopted to date

Proinsulin is stable at room temperature for 24 hours in EDTA:A clinical laboratory analysis (adAPT 3)

AIMS:Reference laboratories advise immediate separation and freezing of samples for the assay of proinsulin, which limit its practicability for smaller centres. Following the demonstration that insulin and C-peptide are stable in EDTA at room temperature for at least 24hours, we undertook simple stability studies to establish whether the same might apply to proinsulin. METHODS:Venous blood samples were drawn from six adult women, some fasting, some not, aliquoted and assayed immediately and after storage at either 4°C or ambient temperature for periods from 2h to 24h. RESULTS:There was no significant variation or difference with storage time or storage condition in either individual or group analysis. CONCLUSION:Proinsulin appears to be stable at room temperature in EDTA for at least 24h. Immediate separation and storage on ice of samples for proinsulin assay is not necessary, which will simplify sample transport, particularly for multicentre trials

Analysis of the profile, characteristics, patient experience and community value of community hospitals : a multimethod study

Background: Community hospitals have been part of England’s health-care landscape since the mid-nineteenth century. Evidence on them has not kept pace with their development. Aim: To provide a comprehensive analysis of the profile, characteristics, patient experience and community value of community hospitals. Design: A multimethod study with three phases. Phase one involved national mapping and the construction of a new database of community hospitals through data set reconciliation and verification. Phase two involved nine case studies, including interviews and focus groups with patients (n = 60), carers (n = 28), staff (n = 132), volunteers (n = 68), community stakeholders (n = 74) and managers and commissioners (n = 9). Phase three involved analysis of Charity Commission data on voluntary support. Setting: Community hospitals in England. Results: The study identified 296 community hospitals with beds in England. Typically, the hospitals were small (<30 beds), in rural communities, led by doctors/general practitioners (GPs) and nurses, without 24/7 on-site medical cover, providing step-down and step-up inpatient care, with an average length of stay of <30 days and a variable range of intermediate care services. Key to patients’ and carers’ experiences of community hospitals was their closeness to ‘home’ through their physical location, environment and atmosphere and the relationships that they support; their provision of personalised, holistic care; and their role in supporting patients through difficult psychological transitions. Communities engage with and support their hospitals through giving time (average = 24 volunteers), raising money (median voluntary income = £15,632), providing services (voluntary and community groups) and giving voice (e.g. communication and consultation). This can contribute to hospital utilisation and sustainability, patient experience, staff morale and volunteer well-being. Engagement varies between and within communities and over time. Community hospitals are important community assets, representing direct and indirect value: instrumental (e.g. health care), economic (e.g. employment), human (e.g. skills development), social (e.g. networks), cultural (e.g. identity and belonging) and symbolic (e.g. vitality and security). Value varies depending on place and time. Limitations: There were limitations to the secondary data available for mapping community hospitals and tracking charitable funds and to our sample of case study respondents, which concentrated on people with a connection to the hospitals. Conclusions: Community hospitals are diverse but are united by a set of common characteristics. Patients and carers experience community hospitals as qualitatively different from other settings. Their accounts highlight the importance of considering the functional, interpersonal, social and psychological dimensions of experience. Community hospitals are highly valued by their local communities, as demonstrated through their active involvement as volunteers and donors. Community hospitals enable the provision of local intermediate care services, delivered through an embedded, relational model of care, which generates deep feelings of reassurance. However, current developments, including the withdrawal of GPs, shifts towards step-down care for non-local patients and changing configurations of services, providers and ownership may undermine this. Future work: Comparative studies of patient experience in different settings, longitudinal studies of community support and value, studies into the implications of changes in community hospital function, GP involvement, provider-mix and ownership and international comparative studies could all be undertaken

Operator theory and function theory in Drury-Arveson space and its quotients

The Drury-Arveson space $H^2_d$, also known as symmetric Fock space or the $d$-shift space, is a Hilbert function space that has a natural $d$-tuple of operators acting on it, which gives it the structure of a Hilbert module. This survey aims to introduce the Drury-Arveson space, to give a panoramic view of the main operator theoretic and function theoretic aspects of this space, and to describe the universal role that it plays in multivariable operator theory and in Pick interpolation theory.Comment: Final version (to appear in Handbook of Operator Theory); 42 page

Novel disease-causing variants and phenotypic features of X-linked megalocornea

Purpose: The aim of the study was to describe the phenotype and molecular genetic causes of X-linked megalocornea (MGC1). We recruited four British, one New Zealand, one Vietnamese and four Czech families. // Methods: All probands and three female carriers underwent ocular examination and Sanger sequencing of the CHRDL1 gene. Two of the probands also had magnetic resonance imaging (MRI) of the brain. // Results: We identified nine pathogenic or likely pathogenic and one variant of uncertain significance in CHRDL1, of which eight are novel. Three probands had ocular findings that have not previously been associated with MGC1, namely pigmentary glaucoma, unilateral posterior corneal vesicles, unilateral keratoconus and unilateral Fuchs heterochromic iridocyclitis. The corneal diameters of the three heterozygous carriers were normal, but two had abnormally thin corneas, and one of these was also diagnosed with unilateral keratoconus. Brain MRI identified arachnoid cysts in both probands, one also had a neuroepithelial cyst, while the second had a midsagittal neurodevelopmental abnormality (cavum septum pellucidum et vergae). // Conclusion: The study expands the spectrum of pathogenic variants and the ocular and brain abnormalities that have been identified in individuals with MGC1. Reduced corneal thickness may represent a mild phenotypic feature in some heterozygous female carriers of CHRDL1 pathogenic variants