Influences on emergency department attendance among frail older people with deteriorating health: a multicentre prospective cohort study.

OBJECTIVES: To examine the patterns and influences on repeated emergency department attendance among frail older people with deteriorating health. STUDY DESIGN: Multicentre prospective cohort study (International Access Rights and Empowerment II study) with convergent mixed methods design. METHODS: Eligible patients were aged ≥65 years, with Clinical Frailty Score ≥5, and ≥1 hospital admission or ≥2 acute attendances in the previous 6 months. Questionnaires were administered to participants over 6 months and we extracted clinical data from the medical records. We conducted modified Poisson multivariable regression analysis to identify factors associated with repeated emergency department attendance (≥2 over 6 months) and thematic analysis of qualitative interviews. RESULTS: A total of 90 participants were recruited. The mean age was 84 years, and 63% were women. Of 87 participants, 21 experienced repeated emergency department attendance. Severe and/or overwhelming pain (adjusted prevalence ratio 2.44, 95% confidence interval 1.17-5.11), greater number of comorbidities (1.32, 1.08-1.62), ≥10 community nursing contacts (2.93, 1.31-6.56), and a total of ≥2 weeks spent in hospital during the previous 6 months (2.91, 1.24-6.84) were associated with repeated attendance. From 45 interviews, we identified influences on emergency department attendance: 1. inaccessibility of community healthcare; 2. perceived barriers to community healthcare seeking; 3. perceived benefits of hospital admission; 4. barriers to recovery during previous hospital admission (unsuitable food, inactivity); and 5. poorly coordinated transitions between settings. CONCLUSIONS: We identified missed opportunities to optimise older people's recovery during hospital admission, such as improved food and a timely and coordinated discharge, which may reduce reattendances. Proactive care in the community with systematic assessment of symptoms may be required, particularly for those with multimorbidity.

The stability of care preferences following acute illness: a mixed methods prospective cohort study of frail older people.

BACKGROUND: Patient preferences are integral to person-centred care, but preference stability is poorly understood in older people, who may experience fluctuant illness trajectories with episodes of acute illness. We aimed to describe, and explore influences on the stability of care preferences in frail older people following recent acute illness. METHODS: Mixed-methods prospective cohort study with dominant qualitative component, parallel data collection and six-month follow up. STUDY POPULATION: age ≥ 65, Rockwood Clinical Frailty score ≥ 5, recent acute illness requiring acute assessment/hospitalisation. Participants rated the importance of six preferences (to extend life, improve quality of life, remain independent, be comfortable, support 'those close to me', and stay out of hospital) at baseline, 12 and 24 weeks using a 0-4 scale, and ranked the most important. A maximum-variation sub-sample additionally contributed serial in-depth qualitative interviews. We described preference stability using frequencies and proportions, and undertook thematic analysis to explore influences on preference stability. RESULTS: 90/192 (45%) of potential participants consented. 82/90 (91%) answered the baseline questionnaire; median age 84, 63% female. Seventeen undertook qualitative interviews. Most participants consistently rated five of the six preferences as important (range 68-89%). 'Extend life' was rated important by fewer participants (32-43%). Importance ratings were stable in 61-86% of cases. The preference ranked most important was unstable in 82% of participants. Preference stability was supported by five influences: the presence of family support; both positive or negative care experiences; preferences being concordant with underlying values; where there was slowness of recovery from illness; and when preferences linked to long term goals. Preference change was related to changes in health awareness, or life events; if preferences were specific to a particular context, or multiple concurrent preferences existed, these were also more liable to change. CONCLUSIONS: Preferences were largely stable following acute illness. Stability was reinforced by care experiences and the presence of family support. Where preferences were unstable, this usually related to changing health awareness. Consideration of these influences during preference elicitation or advance care planning will support delivery of responsive care to meet preferences. Obtaining longer-term data across diverse ethnic groups is needed in future research.

Health Care Workers and Patients as Trojan Horses: a COVID19 ward outbreak.

BACKGROUND: Transmission in healthcare settings can result in significant infections in healthcare workers and patients. Understanding infection dynamics has important implications for methods employed in hospitals to prevent nosocomial transmission events. METHODS: In this case series report we describe a cluster of COVID-19 (Coronavirus disease 2019) in a tertiary care university hospital, in the early phases of the epidemic, after hospital visiting had been stopped and when the UK lockdown was in place. FINDINGS: A 48 year old patient developed COVID-19 31 days post-admission and four days after admission to a medical ward from ITU. Infection was likely acquired from an asymptomatic or minimally symptomatic healthcare worker (HCW). Subsequent investigation over a 14 day period revealed symptoms in 23 staff members and five linked cases in patients on the same ward.Nine of the 23 affected staff members provided care for and had direct exposure with the index case. Four staff reported caring for the index case without use of personal protective equipment. One was coughed on directly by the patient 24 hours prior to the onset of symptoms. CONCLUSION: SARS CoV2 infection can be introduced to a ward area by asymptomatic and minimally symptomatic healthcare workers. Staff members and patients can act as Trojan horses carrying infection into and around the hospital, setting up unexpected transmission events.Transmission of infection from pre-symptomatic, asymptomatic and minimally symptomatic individuals means that universal use of measures to prevent transmission is required for successful reduction of transmission events in the hospital setting.

A public health needs assessment for domestic indoor overheating.

OBJECTIVES: Indoor overheating is a potentially fatal health hazard that was identified as an issue requiring urgent action in the 2017 UK Climate Change Risk Assessment. We aimed to make research on this issue more accessible to local public health teams to encourage its inclusion in local strategic needs assessments. STUDY DESIGN: Epidemiological health needs assessment. METHODS: We adapted established health needs assessment methods, focussing on the epidemiological component, drawing evidence from a non-systematic literature review that was complemented by discussion with experts. RESULTS: Indoor overheating arises from an interaction between occupants' susceptibility to heat, their behaviour and the building's location and its characteristics. Many of these factors are interrelated and, at a national level, are expected to vary over time with demographic and climate change. Understanding these factors, ways to mitigate them and a long-term view are all essential for managing overheating risk. CONCLUSIONS: There is a need for services to be provided at the local level that consider the home environment and its impact on health in all seasons. A population-level approach to risk management across a local area is also useful to inform collaborative efforts to reduce future incidence of overheating and better understand how it varies with socio-economic deprivation.

How many people will need palliative care in 2040? Past trends, future projections and implications for services.

BACKGROUND: Current estimates suggest that approximately 75% of people approaching the end-of-life may benefit from palliative care. The growing numbers of older people and increasing prevalence of chronic illness in many countries mean that more people may benefit from palliative care in the future, but this has not been quantified. The present study aims to estimate future population palliative care need in two high-income countries. METHODS: We used mortality statistics for England and Wales from 2006 to 2014. Building on previous diagnosis-based approaches, we calculated age- and sex-specific proportions of deaths from defined chronic progressive illnesses to estimate the prevalence of palliative care need in the population. We calculated annual change over the 9-year period. Using explicit assumptions about change in disease prevalence over time, and official mortality forecasts, we modelled palliative care need up to 2040. We also undertook separate projections for dementia, cancer and organ failure. RESULTS: By 2040, annual deaths in England and Wales are projected to rise by 25.4% (from 501,424 in 2014 to 628,659). If age- and sex-specific proportions with palliative care needs remain the same as in 2014, the number of people requiring palliative care will grow by 25.0% (from 375,398 to 469,305 people/year). However, if the upward trend observed from 2006 to 2014 continues, the increase will be of 42.4% (161,842 more people/year, total 537,240). In addition, disease-specific projections show that dementia (increase from 59,199 to 219,409 deaths/year by 2040) and cancer (increase from 143,638 to 208,636 deaths by 2040) will be the main drivers of increased need. CONCLUSIONS: If recent mortality trends continue, 160,000 more people in England and Wales will need palliative care by 2040. Healthcare systems must now start to adapt to the age-related growth in deaths from chronic illness, by focusing on integration and boosting of palliative care across health and social care disciplines. Countries with similar demographic and disease changes will likely experience comparable rises in need.

Recreational physical activity in natural environments and implications for health: A population based cross-sectional study in England.

BACKGROUND: Building on evidence that natural environments (e.g. parks, woodlands, beaches) are key locations for physical activity, we estimated the total annual amount of adult recreational physical activity in England's natural environments, and assessed implications for population health. METHODS: A cross-sectional analysis of six waves (2009/10-2014/5) of the nationally representative, Monitor of Engagement with the Natural Environment survey (n=280,790). The survey uses a weekly quota sample, and population weights, to estimate nature visit frequency across England, and provides details on a single, randomly selected visit (n=112,422), including: a) duration; b) activity; and c) environment type. RESULTS: Approximately 8.23 million (95% CIs: 7.93, 8.54) adults (19.5% of the population) made at least one 'active visit' (i.e. ≥30min, ≥3 METs) to natural environments in the previous week, resulting in 1.23 billion (1.14, 1.32) 'active visits' annually. An estimated 3.20 million (3.05, 3.35) of these also reported meeting recommended physical activity guidelines (i.e. ≥5×30min a week) fully, or in part, through such visits. Active visits by this group were associated with an estimated 109,164 (101,736, 116,592) Quality Adjusted Life Years (QALYs) annually. Assuming the social value of a QALY to be £20,000, the annual value of these visits was approximately £2.18 billion (£2.03, £2.33). Results for walking were replicated using WHO's Health Economic Assessment Tool. CONCLUSIONS: Natural environments provide the context for a large proportion of England's recreational physical activity and highlight the need to protect and manage such environments for health purposes.

Minimum indoor temperature threshold recommendations for English homes in winter - A systematic review.

OBJECTIVES: To identify and assess the available evidence on the impacts of cold indoor temperature thresholds on human health and make evidence-based recommendations for English homes. STUDY DESIGN: Systematic literature review. METHODS: A systematic search of peer-reviewed published literature from the UK and countries with similar climates, and grading of the evidence using the National Institute of Health (NIH) framework was followed by a discussion with experts and formulation of recommendations. RESULTS: Twenty papers were included. Studies were included if they were conducted outside England but were from countries considered to have similar climates. Studies included two small randomised controlled trials, two cohort studies and one case control study; other studies were cross-sectional, largely laboratory-based studies. Health effects in the general population start to occur at around 18 °C. Effects in older people are more profound than in younger adults. Older people are less able to perceive low temperatures. DISCUSSION: Although evidence was limited, a strong argument for setting thresholds remains. The effects observed on the general population and the effects on those more vulnerable makes a case for a recommended minimum temperature for all. Health messages should be clear and simple, allowing informed choices to be made. A threshold of 18 °C was considered the evidence based and practical minimum temperature at which a home should be kept during winter in England. CONCLUSION: There is limited evidence available on minimum temperature thresholds for homes. However a recommendation of at least 18 °C for the whole population with nuancing of messages for those more vulnerable to the effects of cold can be made from the results of the retrieved studies. RECOMMENDATION: Heating homes to at least 18 °C (65 °F) in winter poses minimal risk to the health of a sedentary person, wearing suitable clothing.

Surveillance for outbreaks of gastroenteritis in elderly long-term care facilities in France, November 2010 to May 2012.

This article describes outbreaks of gastroenteritis in elderly long-term care facilities (LTCF) in France from November 2010 to May 2012 reported through the surveillance system for gastroenteritis outbreaks in LTCF. A total of 1,072 outbreaks were reported, causing 26,551 episodes of illness and 60 deaths. The median attack rate (AR) among residents was 32%. Norovirus and person-to-person transmission were the most frequently reported aetiology and mode of transmission. Control measures were implemented in 1,054 (98%) outbreaks and for 928 outbreaks, the timing of such measures could be inferred. Of these, 799 (86%) had put control measures into effect within three days of the occurrence of the first case. Outbreaks of gastroenteritis in LTCF cause substantial morbidity and mortality among elderly people in France. LTCF are encouraged to develop infection prevention and control plans and to notify any gastroenteritis outbreak to health authorities to ensure rapid control.

Resistance to teratogenesis by F1 and F2 embryos of PAH-adapted Fundulus heteroclitus is strongly inherited despite reduced recalcitrance of the AHR pathway.

Atlantic killifish (Fundulus heteroclitus) inhabiting the Atlantic Wood Superfund site on the Elizabeth River (Portsmouth, VA, USA) are exposed to a complex mixture of polycyclic aromatic hydrocarbons (PAHs) from former creosote operations, but are resistant to the acute toxicity and cardiac teratogenesis caused by PAHs. The resistance is associated with a dramatic recalcitrance to induction of cytochrome P450 (CYP1) metabolism enzymes following exposure to aryl hydrocarbon receptor (AHR) agonists, along with an elevated antioxidant response and increased expression of several other xenobiotic metabolism and excretion enzymes. However, the heritability of the resistance in the absence of chemical stressors has been inconsistently demonstrated. Understanding the heritability of this resistance will help clarify the nature of population-level responses to chronic exposure to PAH mixtures and aid in identifying the important mechanistic components of resistance to aryl hydrocarbons. We compared the response of Atlantic Wood F1 and F2 embryos to benzo[k]fluoranthene (BkF), benzo[a]pyrene (BaP), 3,3',4,4',5-pentachlorobiphenyl (PCB-126), and a mixture of BkF and fluoranthene (Fl) to that of F1 embryos of reference site killifish. Resistance to cardiac teratogenesis and induction of CYP mRNA expression and CYP activity was determined. We found that both Atlantic Wood F1 and F2 embryos were highly resistance to cardiac teratogenesis. However, the resistance by Atlantic Wood F2 embryos to induction of CYP mRNA expression and enzyme activity was intermediate between that of Atlantic Wood F1 embryos and reference embryos. These results suggest that resistance to cardiac teratogenesis in Atlantic Wood fish is conferred by multiple factors, not all of which appear to be fully genetically heritable.

The impact of thunderstorm asthma on emergency department attendances across London during July 2013.

BACKGROUND: This study illustrates the potential of using emergency department attendance data, routinely accessed as part of a national syndromic surveillance system, to monitor the impact of thunderstorm asthma. METHODS: The Emergency Department Syndromic Surveillance System (EDSSS) routinely monitors anonymised attendance data on a daily basis across a sentinel network of 35 emergency departments. Attendance data for asthma, wheeze and difficulty breathing are analysed on a daily basis. RESULTS: A statistically significant spike in asthma attendances in two EDSSS emergency departments in London was detected on 23 July 2013, coinciding with a series of large violent thunderstorms across southern England. There was also an increase in the reported severity of these attendances. CONCLUSIONS: This preliminary report illustrates the potential of the EDSSS to monitor the impact of thunderstorms on emergency department asthma attendances. Further work will focus on how this system can be used to quantify the impact on emergency departments, thus potentially improving resource planning and also adding to the thunderstorm asthma evidence-base.

Expression of the enteroviral capsid protein VP1 in the islet cells of patients with type 1 diabetes is associated with induction of protein kinase R and downregulation of Mcl-1.

AIMS/HYPOTHESIS: Immunohistochemical staining reveals that the enteroviral capsid protein VP1 is present at higher frequency in the insulin-containing islets of patients with recent-onset type 1 diabetes than in controls. This is consistent with epidemiological evidence suggesting that enteroviral infection may contribute to the autoimmune response in type 1 diabetes. However, immunostaining of VP1 is not definitive since the antibody widely used to detect the protein (Clone 5D8/1) might also cross-react with additional proteins under some conditions. Therefore, we sought to verify that VP1 immunopositivity correlates with additional markers of viral infection. METHODS: Antigen immunoreactivity was examined in formalin-fixed, paraffin-embedded, pancreases from two different collections of type 1 diabetes and control cases: a historical collection from the UK and the nPOD (network of Pancreatic Organ donors with Diabetes) cohort from the USA. RESULTS: VP1 immunoreactivity was present in ~20% of insulin-containing islets of both cohorts under stringent conditions but was absent from insulin-deficient islets. The presence of VP1 was restricted to beta cells but only a minority of these contained the antigen. The innate viral sensor, protein kinase R (PKR) was upregulated selectively in beta cells that were immunopositive for VP1. The anti-apoptotic protein myeloid cell leukaemia sequence-1 (Mcl-1) was abundant in beta cells that were immunonegative for VP1 but Mcl-1 was depleted in cells containing VP1. CONCLUSIONS/INTERPRETATION: The presence of immunoreactive VP1 within beta cells in type 1 diabetes is associated with a cellular phenotype consistent with the activation of antiviral response pathways and enhanced sensitivity to apoptosis. However, definitive studies confirming whether viral infections are causal to beta cell loss in human diabetes are still awaited.

Immunohistochemical analysis of the relationship between islet cell proliferation and the production of the enteroviral capsid protein, VP1, in the islets of patients with recent-onset type 1 diabetes.

AIMS/HYPOTHESIS: The enteroviral capsid protein, VP1, was recently shown to be present in some beta cells in more than 60% of patients with recent-onset type 1 diabetes but in very few age-matched controls. The rate of proliferation of islet cells was also markedly increased in the type 1 diabetic patients. As it has been suggested that enteroviruses replicate most efficiently in proliferating cells, we have investigated whether VP1 is preferentially present in proliferating beta cells in type 1 diabetes. METHODS: Combined immunoperoxidase and immunofluorescence staining was used to record the presence of enteroviral VP1, insulin and Ki67 in the islets of recent-onset type 1 diabetic patients. RESULTS: From a total of 1,175 islets, 359 (30.5%) contained insulin. VP1-producing endocrine cells were found in 72 islets (6.1% of total), all of which retained insulin. Ki67(+) endocrine cells were present in 52 (4.4%) islets, with 44 (84.6%) of these being insulin-positive. Overall, 28 of 1,175 (2.4%) islets contained both Ki67(+) cells and VP1(+) cells. Dual positivity of these markers accounted for 38.9% of the total VP1(+) islets and 53.8% of the total Ki67(+) islets. No individual islet cells were dual-positive for Ki67 and VP1. CONCLUSIONS/INTERPRETATION: Ki67(+) cells were frequently observed in islets that also contained VP1(+) cells, suggesting that the factors facilitating viral replication may also drive islet cell proliferation. However, in an individual cell, VP1 production does not require concurrent beta cell proliferation.

The risk of variant Creutzfeldt-Jakob disease among UK patients with bleeding disorders, known to have received potentially contaminated plasma products.

The risk of variant Creutzfeldt-Jakob disease (vCJD) from potentially infected plasma products remains unquantified. This risk has been assessed for 787 UK patients with an inherited bleeding disorder prospectively followed-up for 10-20 years through the UK Haemophilia Centre Doctors' Organisation (UKHCDO) Surveillance Study. These patients had been treated with any of 25 'implicated' clotting factor batches from 1987 to 1999, which included in their manufacture, plasma from eight donors who subsequently developed clinical vCJD. Variant CJD infectivity of these batches was estimated using plasma fraction infectivity estimates and batch-manufacturing data. Total potential vCJD infectivity received by each patient has been estimated by cumulating estimated infectivity from all doses received during their lifetime. Of 787 patients, 604 (77%) were followed-up for over 13 years following exposure to an implicated batch. For these 604 patients, the estimated vCJD risk is ≥ 1% for 595, ≥ 50% for 164 and 100% for 51. This is additional to background UK population risk due to dietary exposure. Of 604 patients, 94 (16%) received implicated batches linked to donors who developed clinical vCJD within 6 months of their donations. One hundred and fifty-one (25%) had received their first dose when under 10 years of age. By 1st January 2009, none of these patients had developed clinical vCJD. The absence of clinical vCJD cases in this cohort to date suggests that either plasma fraction infectivity estimates are overly precautionary, or the incubation period is longer for this cohort than for implicated cellular blood product recipients. Further follow-up of this cohort is needed.

Nationwide outbreak of Salmonella enterica serotype 4,12:i:- infections in France, linked to dried pork sausage, March-May 2010.

In May 2010, a nationwide excess of infections with the specific monophasic variant Salmonella enterica serotype 4,12:i:- was investigated in France. Subtyping with multilocus variable number of tandem repeats analysis revealed a distinct epidemic strain within this excess. Epidemiological investigations identified a dried pork sausage sold by a particular chain of supermarkets as the likely vehicle of transmission. The suspected batches have been withdrawn and recalled.

Evidence of increased islet cell proliferation in patients with recent-onset type 1 diabetes.

AIMS/HYPOTHESIS: In adults, the rate of beta cell replication is normally very low, but recent evidence suggests that it may increase during insulitis. We therefore studied tissue from donors with recent-onset type 1 diabetes to establish whether islet cell proliferation is increased during the disease process. METHODS: Paraffin-embedded pancreatic sections from ten donors with recent-onset type 1 diabetes and a range of relevant controls were stained by immunohistochemical techniques with antibodies against the proliferation markers Ki67 and minichromosome maintenance protein-2 (MCM-2). A combination staining technique involving immunoperoxidase and immunofluorescence methods was developed to quantify the numbers of alpha and beta cells with Ki67-positive nuclei and to investigate the relationship between insulitis and islet cell proliferation. RESULTS: In non-diabetic control donors, only 1.1 +/- 0.3% (mean +/- SEM) of islets contained one or more Ki67(+) islet cells, whereas this proportion was increased markedly in recent-onset type 1 diabetes (10.88 +/- 2.5%; p < 0.005). An equivalent increase in Ki67(+) staining occurred in alpha and beta cells and was correlated positively with the presence of insulitis. A significant increase in the labelling of islet cells from type 1 diabetic donors was also seen when MCM-2 staining was employed. Increased islet cell proliferation was not evident in three donors with longer duration type 1 diabetes or in ten type 2 diabetic donors. CONCLUSIONS/INTERPRETATION: Alpha and beta cells undergo a marked increase in proliferation during the progression of type 1 diabetes in humans. The results imply that islet cell proliferation is re-initiated in response to the autoimmune attack associated with type 1 diabetes.

The prevalence of enteroviral capsid protein vp1 immunostaining in pancreatic islets in human type 1 diabetes.

AIMS/HYPOTHESIS: Evidence that the beta cells of human patients with type 1 diabetes can be infected with enterovirus is accumulating, but it remains unclear whether such infections occur at high frequency and are important in the disease process. We have now assessed the prevalence of enteroviral capsid protein vp1 (vp1) staining in a large cohort of autopsy pancreases of recent-onset type 1 diabetic patients and a range of controls. METHODS: Serial sections of paraffin-embedded pancreatic autopsy samples from 72 recent-onset type 1 diabetes patients and up to 161 controls were immunostained for insulin, glucagon, vp1, double-stranded RNA activated protein kinase R (PKR) and MHC class I. RESULTS: vp1-immunopositive cells were detected in multiple islets of 44 out of 72 young recent-onset type 1 diabetic patients, compared with a total of only three islets in three out of 50 neonatal and paediatric normal controls. vp1 staining was restricted to insulin-containing beta cells. Among the control pancreases, vp1 immunopositivity was also observed in some islets from ten out of 25 type 2 diabetic patients. A strong correlation was established between islet cell vp1 positivity and PKR production in insulin-containing islets of both type 1 and type 2 diabetic patients, consistent with a persistent viral infection of the islets. CONCLUSIONS/INTERPRETATION: Immunoreactive vp1 is commonly found in the islets of recent-onset type 1 diabetes patients, but only rarely in normal paediatric controls. vp1 immunostaining was also observed in some islets of type 2 diabetes patients, suggesting that the phenomenon is not restricted to type 1 diabetes patients.

Analysis of islet inflammation in human type 1 diabetes.

The immunopathology of type 1 diabetes (T1D) has proved difficult to study in man because of the limited availability of appropriate samples, but we now report a detailed study charting the evolution of insulitis in human T1D. Pancreas samples removed post-mortem from 29 patients (mean age 11.7 years) with recent-onset T1D were analysed by immunohistochemistry. The cell types constituting the inflammatory infiltrate within islets (insulitis) were determined in parallel with islet insulin content. CD8(+) cytotoxic T cells were the most abundant population during insulitis. Macrophages (CD68(+)) were also present during both early and later insulitis, although in fewer numbers. CD20(+) cells were present in only small numbers in early insulitis but were recruited to islets as beta cell death progressed. CD138(+) plasma cells were infrequent at all stages of insulitis. CD4(+) cells were present in the islet infiltrate in all patients but were less abundant than CD8(+) or CD68(+) cells. Forkhead box protein P3(+) regulatory T cells were detected in the islets of only a single patient. Natural killer cells were detected rarely, even in heavily inflamed islets. The results suggest a defined sequence of immune cell recruitment in human T1D. They imply that both CD8(+) cytotoxic cells and macrophages may contribute to beta cell death during early insulitis. CD20(+) cells are recruited in greatest numbers during late insulitis, suggesting an increasing role for these cells as insulitis develops. Natural killer cells and forkhead box protein P3(+) T cells do not appear to be required for beta cell death.