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Cellular therapies for the treatment of immune-mediated GI and liver disease.
No full textINTRODUCTION
Immune-mediated liver and gastrointestinal diseases are chronic conditions that lack curative treatments. Despite advances in the understanding and treatment of these conditions, they frequently remain refractory to treatment and represent a significant unmet need. Cellular therapies are an emerging option and hold the potential to have a major impact.
DATA SOURCES
A literature review was carried out using Pubmed. Keywords used for search were 'ATMP', 'immune mediated', 'autoimmune liver disease' and 'immune mediated gastrointestinal conditions', 'cell therapy', 'MSC', 'HSCT', 'Regulatory T cells', 'GVHD', 'Coeliac disease' 'IBD', 'PSC', 'AIH', 'PBC'. No new data were generated or analysed in support of this review.
AREAS OF AGREEMENT
There is substantial evidence from clinical trials to support the use of cell therapies as a treatment for immune-mediated liver and gastrointestinal conditions. Cellular therapy products have the ability to 'reset' the dysregulated immune system and this in turn can offer a longer term remission. There are ongoing clinical trials with mesenchymal stromal cells (MSCs) and other cells to evidence their efficacy profile and fill the gaps in current knowledge. Insights gained will inform future trial designs and subsequent therapeutic applications.
AREAS OF CONTROVERSY
There remains some uncertainty around the extrapolation of results from animal studies to clinical trials. Longevity of the therapeutic effects seen after the use of cell therapy needs to be scrutinized further. Heterogeneity in the selection of cells, source, methods of productions and cell administration pose challenges to the interpretation of the data.
GROWING POINTS
MSCs are emerging as a key therapeutic cells in immune-mediated liver and gastrointestinal conditions. Ongoing trials with these cells will provide new insights and a better understanding thus informing future larger scale studies.
AREAS TIMELY FOR DEVELOPING RESEARCH
Larger scale clinical trials to build on the evidence from small studies regarding safety and efficacy of cellular therapy are still needed before cellular therapies can become off the shelf treatments. Alignment of academia and industry to standardize the processes involved in cell selection, manipulation and expansion and subsequent use in clinical trials is an important avenue to explore further
Assembly Line ICU: what the Long Shops taught us about managing surge capacity for COVID-19.
No full textOBJECTIVES
To safely expand and adapt the normal workings of a large critical care unit in response to the COVID-19 pandemic.
METHODS
In April 2020, UK health systems were challenged to expand critical care capacity rapidly during the first wave of the COVID-19 pandemic so that they could accommodate patients with respiratory and multiple organ failure. Here, we describe the preparation and adaptive responses of a large critical care unit to the oncoming burden of disease. Our changes were similar to the revolution in manufacturing brought about by 'Long Shops' of 1853 when Richard Garrett and Sons of Leiston started mass manufacture of traction engines. This innovation broke the whole process into smaller parts and increased productivity. When applied to COVID-19 preparations, an assembly line approach had the advantage that our ICU became easily scalable to manage an influx of additional staff as well as the increase in admissions. Healthcare professionals could be replaced in case of absence and training focused on a smaller number of tasks.
RESULTS
Compared with the equivalent period in 2019, the ICU provided 30.9% more patient days (2599 to 3402), 1845 of which were ventilated days (compared with 694 in 2019, 165.8% increase) while time from first referral to ICU admission reduced from 193.8±123.8 min (±SD) to 110.7±76.75 min (±SD). Throughout, ICU maintained adequate capacity and also accepted patients from neighbouring hospitals. This was done by managing an additional 205 doctors (70% increase), 168 nurses who had previously worked in ICU and another 261 nurses deployed from other parts of the hospital (82% increase).Our large tertiary hospital ensured a dedicated non-COVID ICU was staffed and equipped to take regional emergency referrals so that those patients requiring specialist surgery and treatment were treated throughout the COVID-19 pandemic.
CONCLUSIONS
We report how the challenge of managing a huge influx of patients and redeployed staff was met by deconstructing ICU care into its constituent parts. Although reported from the largest colocated ICU in the UK, we believe that this offers solutions to ICUs of all sizes and may provide a generalisable model for critical care pandemic surge planning
Mental health symptoms in a cohort of hospital healthcare workers following the first peak of the COVID-19 pandemic in the UK.
No full textBACKGROUND
The coronavirus disease 2019 (COVID-19) pandemic is likely to lead to a significant increase in mental health disorders among healthcare workers (HCW).
AIMS
We evaluated the rates of anxiety, depressive and post-traumatic stress disorder (PTSD) symptoms in a population of HCW in the UK.
METHOD
An electronic survey was conducted between the 5 June 2020 and 31 July 2020 of all hospital HCW in the West Midlands, UK using clinically validated questionnaires: the 4-item Patient Health Questionnaire(PHQ-4) and the Impact of Event Scale-Revised (IES-R). Univariate analyses and adjusted logistic regression analyses were performed to estimate the strengths in associations between 24 independent variables and anxiety, depressive or PTSD symptoms.
RESULTS
There were 2638 eligible participants who completed the survey (female: 79.5%, median age: 42 years, interquartile range: 32-51). The rates of clinically significant symptoms of anxiety, depression and PTSD were 34.3%, 31.2% and 24.5%, respectively. In adjusted analysis a history of mental health conditions was associated with clinically significant symptoms of anxiety (odds ratio (OR) = 2.3, 95% CI 1.9-2.7, P < 0.001), depression (OR = 2.5, 95% CI 2.1-3.0, P < 0.001) and PTSD (OR = 2.1, 95% CI 1.7-2.5, P < 0.001). The availability of adequate personal protective equipment (PPE), well-being support and lower exposure to moral dilemmas at work demonstrated significant negative associations with these symptoms (P ≤ 0.001).
CONCLUSIONS
We report higher rates of clinically significant mental health symptoms among hospital HCW following the initial COVID-19 pandemic peak in the UK. Those with a history of mental health conditions were most at risk. Adequate PPE availability, access to well-being support and reduced exposure to moral dilemmas may protect hospital HCW from mental health symptoms
Author response to: Comment on: Impact of bariatric surgery on cardiovascular outcomes and mortality: a population-based cohort study.
No full textAn exploration into experiences and attitudes regarding risky health behaviours in an adult cystic fibrosis population.
No full textHealth risk behaviours (HRBs) are prevalent within the cystic fibrosis (CF) population, and there is a lack of research around what influences their engagement. This research explored beliefs associated with HRBs within an adult CF population using qualitative semi-structured interviews. Participants' beliefs towards their CF and its life impact were investigated to explore reasons for engaging in HRB. A desire for normalcy was evident, often accompanied by engagement in everyday HRB as a method of minimising the illness identity. Evidence of a life-orientated illness perspective was also prevalent, with participants engaging in some risky behaviours for fun. Overall, there was a lack of knowledge on the consequences of HRB, with many participants reporting not being informed of these by clinicians. This research highlights a dilemma between clinical recommendations and personal life strategies undertaken by individuals with CF to support their identity
Validation of subscales of the Severe Asthma Questionnaire (SAQ) using exploratory factor analysis (EFA).
No full textBACKGROUND
The Severe Asthma Questionnaire (SAQ) is a health related quality of life (HRQoL) questionnaire validated for use in severe asthma. It is scored using the mean value of 16 items (SAQ score) in addition to a single item global rating of HRQoL (SAQ-global). The aim was to validate clinically relevant subscales using exploratory factor analysis (EFA).
METHODS
The SAQ was completed, along with measures of asthma control and EQ5D-5L by patients attending six UK severe asthma centres. Clinical data were included in the analysis. EFA using principal axis factoring and oblimin rotation was used to achieve simple structure of data.
RESULTS
460 patients with severe asthma participated, 65% women, mean age 51 (16-83) years. A three factor solution achieved best fit and showed that the SAQ items formed three distinct but inter-correlated groups of items where items were grouped in a way that was consistent with item content. The three subscales were differentially associated with clinically relevant variables (lung function and mood). Males and females interpreted the question of night disturbance in different ways.
CONCLUSIONS
This paper provides a template for best practice in the use of EFA when validating HRQoL subscales. The SAQ can be scored as three subscales with content reflecting three different constructs people with severe asthma use when making judgements about their lives. The subscale 'My Life' assesses the impact of severe asthma on different life activities, 'My Mind' assesses the perceived emotional impact and 'My Body' the impact of extra-pulmonary symptoms and side effects
Distally-based Peroneus Brevis Turnover Muscle Flap in the Reconstruction of Soft Tissue Defects.
No full textReconstruction of the distal 3rd of the lower leg requires either local or free flap coverage if tendons or bones are exposed. The distally based, pedicled peroneus brevis (PB) flap has been shown to be a valid option in the management of distal 3rd lower limb injuries. Herein, we present 21 cases treated with distally-based PB muscle flaps between May 2017 and September 2019. The defect location varied, and included defects over the lateral and medial malleolar areas, distal tibia (middle and distal 3rd junction, and the distal 3rd), and Achilles tendon area.
Methods
The PB was dissected from the lateral fibula and intermuscular septa in a cephalic to caudal direction, to a point no lower than 7 cm proximal to the lateral malleolus tip. This preserved most distal vascular perforators to the muscle, and afforded sufficient mobilization to allow successful turn-over of the muscle, with transposition into the defect within 30 minutes of tourniquet time. A meshed skin graft completed the intervention.
Results
The metalwork was removed in all chronic cases (10/21), as bone union had occurred. All flaps survived completely. One patient partially lost the skin graft; the wound was healed by secondary intention. No major complications occurred and no significant patient discomfort was noted. All wounds healed completely by 9 weeks of follow-up.
Conclusion
The PB turnover muscle flap is a versatile flap, ideally suited to manage up to moderately sized defects of the distal 3rd of the lower leg, with negligible postoperative morbidity
Negative impact of COVID-19 lockdown on papilloedema and idiopathic intracranial hypertension.
No full textSelf-reported Pruritus and Clinical, Dialysis-Related, and Patient-Reported Outcomes in Hemodialysis Patients.
No full textRationale & Objective
Chronic kidney disease (CKD)-associated pruritus, generalized itching related to CKD, affects many aspects of hemodialysis patients' lives. However, information regarding the relationship between pruritus and several key outcomes in hemodialysis patients remains limited.
Study Design
Prospective cohort.
Setting & Participants
23,264 hemodialysis patients from 21 countries in the Dialysis Outcomes and Practice Patterns Study (DOPPS) phases 4 to 6 (2009-2018).
Exposure
Pruritus severity, based on self-reported degree to which patients were bothered by itchy skin (5-category ordinal scale from "not at all" to "extremely").
Outcomes
Clinical, dialysis-related, and patient-reported outcomes.
Analytical Approach
Cox regression for time-to-event outcomes and modified Poisson regression for binary outcomes, adjusted for potential confounders.
Results
The proportion of patients at least moderately bothered by pruritus was 37%, and 7% were extremely bothered. Compared with the reference group ("not at all"), the adjusted mortality HR for patients extremely bothered by pruritus was 1.24 (95% CI, 1.08-1.41). Rates of cardiovascular and infection-related deaths and hospitalizations were also higher for patients extremely versus not at all bothered by pruritus (HR range, 1.17-1.44). Patients extremely bothered by pruritus were also more likely to withdraw from dialysis and miss hemodialysis sessions and were less likely to be employed. Strong monotonic associations were observed between pruritus severity and longer recovery time from a hemodialysis session, lower physical and mental quality of life, increased depressive symptoms, and poorer sleep quality.
Limitations
Residual confounding, recall bias, nonresponse bias.
Conclusions
Our findings demonstrate how diverse and far-reaching poor outcomes are for patients who experience CKD-associated pruritus, specifically those with more severe pruritus. There is need for change in practice patterns internationally to effectively identify and treat patients with pruritus to reduce symptom burden and improve quality of life and possibly even survival
Nutrition in alcohol-related liver disease: Physiopathology and management.
No full textMalnutrition encompassing both macro- and micro-nutrient deficiency, remains one of the most frequent complications of alcohol-related liver disease (ArLD). Protein-energy malnutrition can cause significant complications including sarcopenia, frailty and immunodepression in cirrhotic patients. Malnutrition reduces patient's survival and negatively affects the quality of life of individuals with ArLD. Moreover, nutritional deficit increases the likelihood of hepatic decompensation in cirrhosis. Prompt recognition of at-risk individuals, early diagnosis and treatment of malnutrition remains a key component of ArLD management. In this review, we describe the pathophysiology of malnutrition in ArLD, review the screening tools available for nutritional assessment and discuss nutritional management strategies relevant to the different stages of ArLD, ranging from acute alcoholic hepatitis through to decompensated end stage liver disease