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Superior Aerobic Capacity and Indices of Skeletal Muscle Morphology in Chronically Trained Master Endurance Athletes Compared with Untrained Older Adults.
No full textThe study aim was to comprehensively assess physiological function and muscle morphology in chronically-trained older individuals against untrained young and older individuals. In a cross-sectional design 15 young untrained controls (YC) (20±2.7 y, 78.9±13.3kg), 12 untrained older controls (OC) (69.8±4.1 y, 77.5±14.2kg) and 14 endurance-trained master athletes (MA) (67.1±4.1 y, 68.7±6.5kg) underwent assessments of body composition, aerobic capacity, strength, muscle architecture and fibre-type morphology. Skeletal muscle index was lower and body fat greater in OC vs. MA. Estimated VO2max (ml·kg-1·min-1) was similar between MA and YC, but lower in OC. Isometric leg strength normalized to fat-free mass was similar between groups, whereas normalized isometric arm strength was greater in YC than MA. Myosin heavy chain (MHC) I fibre area was greater in MA than OC, whilst MHC II fibre area was greater in YC than OC. MHC II fibre myonuclear domain size was greater in YC than OC and MA, whereas MA had greater MHC I and MHC II fibre capilliarisation than OC and YC. Satellite cell content was similar between groups. Chronic endurance training enhances indices of muscle morphology and improves body composition and aerobic capacity in older age, with potentially important implications for healthspan extension
Development of practical recommendations for diagnostic accuracy studies in low prevalence situations.
No full textOBJECTIVE
Low disease prevalence poses challenges for diagnostic accuracy studies because of the large sample sizes that are required in order to obtain sufficient precision. The aim is to collate and discuss designs of diagnostic accuracy studies suited for use in low prevalence situations.
STUDY DESIGN AND SETTING
We conducted a literature search including backward citation tracking and expert consultation. Two reviewers independently selected studies on designs for estimating diagnostic accuracy in a low prevalence situation. During a one-day expert meeting, all designs were discussed and recommendations were formulated.
RESULTS
We identified six designs for diagnostic accuracy studies that are suitable in low prevalence situations, because they reduced the total sample size or the number of patients undergoing the index test or reference standard depending on which poses the highest burden. We described the advantages and limitations of these designs and evaluated efficiencies in sample sizes, risk of bias and alignment with the clinical pathway for applicability in routine care.
CONCLUSION
Choosing a study design for diagnostic accuracy studies in low prevalence situations should depend on whether the aim is to limit the number of patients undergoing the index test or reference standard, and the risk of bias associated with a particular design type
Fatigue in primary Sjögren's syndrome (pSS) is associated with lower levels of proinflammatory cytokines: a validation study.
No full textPrimary Sjögren's syndrome (pSS) is a chronic autoimmune rheumatic disease with symptoms including dryness, fatigue, and pain. The previous work by our group has suggested that certain proinflammatory cytokines are inversely related to patient-reported levels of fatigue. To date, these findings have not been validated. This study aims to validate this observation. Blood levels of seven cytokines were measured in 120 patients with pSS from the United Kingdom Primary Sjögren's Syndrome Registry and 30 age-matched healthy non-fatigued controls. Patient-reported scores for fatigue were classified according to severity and compared to cytokine levels using analysis of variance. The differences between cytokines in cases and controls were evaluated using Wilcoxon test. A logistic regression model was used to determine the most important identifiers of fatigue. Five cytokines, interferon-γ-induced protein-10 (IP-10), tumour necrosis factor-α (TNFα), interferon-α (IFNα), interferon-γ (IFN-γ), and lymphotoxin-α (LT-α) were significantly higher in patients with pSS (n = 120) compared to non-fatigued controls (n = 30). Levels of two proinflammatory cytokines, TNF-α (p = 0.021) and LT-α (p = 0.043), were inversely related to patient-reported levels of fatigue. Cytokine levels, disease-specific and clinical parameters as well as pain, anxiety, and depression were used as predictors in our validation model. The model correctly identifies fatigue levels with 85% accuracy. Consistent with the original study, pain, depression, and proinflammatory cytokines appear to be the most powerful predictors of fatigue in pSS. TNF-α and LT-α have an inverse relationship with fatigue severity in pSS challenging the notion that proinflammatory cytokines directly mediate fatigue in chronic immunological conditions
Obesity in acute alcoholic hepatitis increases morbidity and mortality.
No full textBACKGROUND
Alcohol and obesity synergise to increase the risk of liver-related mortality. We examined the influence of adiposity on clinical outcomes in alcoholic hepatitis (AH) and the underlying inflammatory crosstalk between adipose tissue (AT) and the liver.
METHODS
A cohort of 233 patients with AH from the UK and USA provided data to analyse the effects of obesity in AH. Body mass index was corrected for the severity of ascites, termed cBMI. Inflammatory and metabolic profiling was undertaken by proteome analysis of human serum samples. The effect of alcohol on adipose tissue and CXCL11 expression was studied in 3 T3-derived adipocytes and in mice using the high-fat diet-plus-binge ethanol model.
FINDINGS
Obesity was common amongst patients with AH, seen in 19% of individuals. Obesity (HR 2.22, 95%CI 1.1-4.3, p = .022) and underweight (HR 2.38, 1.00-5.6, p = .049) were independently associated with mortality at 3 months. Proteome analysis demonstrated multiple metabolic and inflammatory factors differentially expressed in obese AH verse lean AH, with CXCL11 being the most elevated factor in obese AH. In vitro analysis of cultured adipocytes and in vivo analysis of mouse models showed that alcohol induced CXCL11 expression in AT, but not in liver.
INTERPRETATION
Obesity is common in AH and associated with a greater than two-fold increase in short-term mortality. Obese AH is associated with a different inflammatory phenotype, with the greatest elevation in CXCL11. These data confirm that adiposity is clinically important in acute alcohol-related liver disease and illustrate the adipose-liver inflammatory axis in AH. FUND: This work was supported in part by an EASL Sheila Sherlock Physician Scientist Fellowship. The funder played no role in gathering or analysing data or writing the manuscript. This paper presents independent research supported by the NIHR Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care
Management of Pediatric Condyle Fractures.
No full textINTRODUCTION
Mandibular condyle fractures are a common type of facial fracture in children. The authors aimed to examine the demographics, etiology, treatment, and outcomes of these fractures managed in a single pediatric trauma unit.
MATERIALS AND METHODS
A retrospective review was performed of patients presenting to a pediatric hospital between 2003 and 2016 with mandibular condyle fractures. Initial data was extracted from a dedicated trauma database. Included patient's medical records and imaging were then reviewed. Data on demographics, etiology, fracture type, and treatment were recorded. Univariate statistical analysis was performed.
RESULTS
Forty-four patients with 49 condyle fractures were included. The average age of patients was 11.4 years (range 3-15 years). A fall from a bicycle/scooter was the most common mechanism. Twenty-six fractures were isolated and 23 involved a further fracture of the mandibular arch. The condylar neck was the most common site of fracture (55%). There was no statistical significance between age (0-10 years, 10-16 years) and site of fracture or the presence of an associated arch fracture. The majority of isolated fractures (73%) were treated conservatively without inter-maxillary fixation. Thirty-nine patients attended the follow-up and the median follow-up period was 196 days (interquartile range 21-165 days). Two patients had a malocclusion at follow-up that required intervention.
CONCLUSION
There was a broad range of presentations in our cohort. Conservative management in isolated fractures resulted in stable outcomes and this large case series supports the consensus that management of pediatric condyle fractures should be as conservative as possible
Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review.
No full textAdvances in technology have allowed for the sensitive, specific, and simultaneous quantitative profiling of steroid precursors, bioactive steroids and inactive metabolites, facilitating comprehensive characterization of the serum and urine steroid metabolomes. The quantification of steroid panels are therefore gaining favor over quantification of single marker metabolites in the clinical and research laboratories. However, although the biochemical pathways for the biosynthesis and metabolism of steroid hormones are now well defined, a gulf still exists between this knowledge and its application to the measured steroid profiles. In this review, we present an overview of steroid hormone biosynthesis and metabolism by the liver and peripheral tissues, specifically highlighting the pathways linking and differentiating the serum and urine steroid metabolomes. A brief overview of the methodology used in steroid profiling is also provided
The challenge of managing mild to moderate distress in patients with end stage renal disease: results from a multi-centre, mixed methods research study and the implications for renal service organisation.
No full textBACKGROUND
Lower-level emotional and psychological difficulties ('distress') in patients with end stage renal disease (ESRD), can lead to reduced quality of life and poor clinical outcomes. National guidelines mandate provision of emotional and psychological support for renal patients yet little is known about the support that patients may require, or the challenges that staff experience in identifying and responding to patient distress.
METHODS
Mixed methods study in renal units at four NHS Trusts in the West Midlands, UK involving cross-sectional surveys of ESRD patients and renal unit staff and semi-structured interviews with 46 purposively-sampled patients and 31 renal unit staff. Interviews explored patients' experience of distress and personal coping strategies, staff attitudes towards patient distress and perceptions of their role, responsibility and capacity.
RESULTS
Patient distress was widespread (346/1040; 33.3%), and emotional problems were frequently reported. Younger patients, females, those from black and minority ethnic (BME) groups and patients recently initiating dialysis reported particular support needs. Staff recognised the value of supporting distressed patients, yet support often depended on individual staff members' skills and personal approach. Staff reported difficulties with onward referral to formal counselling and psychology services and a lack of immediate access to less formalised options. There was also a substantial training/skills gap whereby many staff reported lacking the confidence to recognise and respond to patient distress. Staff fell broadly into three groups: 'Enthusiasts' who considered identifying and responding to patient distress as integral to their role; 'Equivocators' who thought that managing distress was part of their role, but who lacked skills and confidence to do this effectively, and 'Avoiders' who did not see managing distress as part of their role and actively avoided the issue with patients.
CONCLUSIONS
Embedding the value of emotional support provision into renal unit culture is the key to 'normalising' discussions about distress. Immediately accessible, informal support options should be available, and all renal staff should be offered training to proactively identify and reactively manage patient distress. Emotional support for staff is important to ensure that a greater emphasis on managing patient distress is not associated with an increased incidence of staff burnout
HEART UK consensus statement on Lipoprotein(a): A call to action.
No full textLipoprotein(a), Lp(a), is a modified atherogenic low-density lipoprotein particle that contains apolipoprotein(a). Its levels are highly heritable and variable in the population. This consensus statement by HEART UK is based on the evidence that Lp(a) is an independent cardiovascular disease (CVD) risk factor, provides recommendations for its measurement in clinical practice and reviews current and emerging therapeutic strategies to reduce CVD risk. Ten statements summarise the most salient points for practitioners and patients with high Lp(a). HEART UK recommends that Lp(a) is measured in adults as follows: 1) those with a personal or family history of premature atherosclerotic CVD; 2) those with first-degree relatives who have Lp(a) levels >200 nmol/l; 3) patients with familial hypercholesterolemia; 4) patients with calcific aortic valve stenosis and 5) those with borderline (but <15%) 10-year risk of a cardiovascular event. The management of patients with raised Lp(a) levels should include: 1) reducing overall atherosclerotic risk; 2) controlling dyslipidemia with a desirable non-HDL-cholesterol level of <100 mg/dl (2.5 mmol/l) and 3) consideration of lipoprotein apheresis
Optical coherence tomography (OCT) in unconscious and systemically unwell patients using a mobile OCT device: a pilot study.
No full textOBJECTIVE
This study aims to evaluate the feasibility of retinal imaging in critical care using a novel mobile optical coherence tomography (OCT) device. The Heidelberg SPECTRALIS FLEX module (Heidelberg Engineering, Heidelberg, Germany) is an OCT unit with a boom arm, enabling ocular OCT assessment in less mobile patients.
DESIGN
We undertook an evaluation of the feasibility of using the SPECTRALIS FLEX for undertaking ocular OCT images in unconscious and critically ill patients.
SETTING
This study was conducted in the critical care unit of a large tertiary referral unit in the United Kingdom.
PARTICIPANTS
13 systemically unwell patients admitted to the critical care unit were purposively sampled to enable evaluation in patients with a range of clinical states.
OUTCOME MEASURES
The primary outcome was the feasibility of acquiring clinically interpretable OCT scans on a consecutive series of patients. The standardised scanning protocol included macula-focused OCT, OCT optic nerve head (ONH), OCT angiography (OCTA) of the macula and ONH OCTA.
RESULTS
OCT images from 13 patients were attempted. The success rates of each scan type are 84% for OCT macula, 76% for OCT ONH, 56% for OCTA macula and 36% for OCTA ONH. The overall mean success rate of scans per patient was 64% (95% CI 46% to 81%). Clinicians reported clinical value in 100% scans which were successfully obtained, including both ruling in and ruling out relevant ocular complications such as corneal thinning, macular oedema and optic disc swelling. The most common causes of failure to achieve clinically interpretable scans were inadequately sustained OCT alignment in delirious patients and a compromised ocular surface due to corneal exposure.
CONCLUSIONS
This prospective evaluation indicates the feasibility and potential clinical value of the SPECTRALIS FLEX OCT system on the critical care unit. Portable OCT systems have the potential to bring instrument-based ophthalmic assessment to critically ill patients, enabling detection and micron-level monitoring of ocular complications