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  • Feedback control in hemodialysis

    Randhay, Ashveer; Eldehni, Mohamed; Selby, Nicholas
    A number of systems of feedback control during dialysis have been developed, which have the shared characteristic of prospectively measuring physiological parameters and then automatically altering dialysis parameters in real time according to a pre-specified dialysis prescription. These include feedback systems aimed at reducing intradialytic hypotension based on relative blood volume monitoring linked to adjustments in ultrafiltration and dialysate conductivity, and blood temperature monitoring linked to alterations in dialysate temperature. Feedback systems also exist that manipulate sodium balance during dialysis by assessing and adjusting dialysate conductivity. In this review article, we discuss the rationale for automated feedback systems during dialysis, describe how the different feedback systems work, and provide a review of the current evidence on their clinical effectiveness.
  • Serum anti-tissue transglutaminase IgA and prediction of duodenal villous atrophy in adults with suspected coeliac disease without IgA deficiency (Bi.A.CeD): a multicentre, prospective cohort study.

    Holmes, Geoffrey
    BACKGROUND: Whether coeliac disease in adults can be diagnosed with serology alone remains controversial. We aimed to evaluate the accuracy of serum anti-tissue transglutaminase IgA (tTG-IgA) in the diagnosis of coeliac disease. METHODS: In this multicentre, prospective cohort study, adult participants (aged ≥18 years) with suspected coeliac disease without IgA deficiency who were not on a gluten-free diet and who had a local serum tTG-IgA measurement, were enrolled from Feb 27, 2018, to Dec 24, 2020, by 14 tertiary referral centres (ten from Europe, two from Asia, one from Oceania, and one from South America) to undergo local endoscopic duodenal biopsy. Local serum tTG-IgA was measured with 14 different test brands and concentration expressed as a multiple of each test's upper limit of normal (ULN), and defined as positive when greater than 1 times the ULN. The main study outcome was the reliability of serum tests for the diagnosis of coeliac disease, as defined by duodenal villous atrophy (Marsh type 3 or Corazza-Villanacci grade B). Histology was evaluated by the local pathologist, with discordant cases (positive tTG-IgA without duodenal villous atrophy or negative tTG-IgA with duodenal villous atrophy) re-evaluated by a central pathologist. The reliability of serum tests for the prediction of duodenal villous atrophy was evaluated according to sensitivity, specificity, positive predictive value, negative predictive value, and the area under the receiver operating characteristic curve (AUC) for categorical and continuous data. FINDINGS: We enrolled 436 participants with complete local data on serum tTG-IgA and duodenal histology (296 [68%] women and 140 [32%] men; mean age 40 years [SD 15]). Positive serum tTG-IgA was detected in 363 (83%) participants and negative serum tTG-IgA in 73 (17%). Of the 363 participants with positive serum tTG-IgA, 341 had positive histology (true positives) and 22 had negative histology (false positives) after local review. Of the 73 participants with negative serum tTG-IgA, seven had positive histology (false negatives) and 66 had negative histology (true negatives) after local review. The positive predictive value was 93·9% (95% CI 89·2-98·6), the negative predictive value was 90·4% (85·5-95·3), sensitivity was 98·0% (95·3-100·0), and specificity was 75·0% (66·6-83·4). After central re-evaluation of duodenal histology in 29 discordant cases, there were 348 true positive cases, 15 false positive cases, 66 true negative cases, and seven false negative cases, resulting in a positive predictive value of 95·9% (92·0-99·8), a negative predictive value of 90·4% (85·5-95·3), a sensitivity of 98·0% (95·3-100·0), and a specificity of 81·5% (73·9-89·1). Either using the local or central definition of duodenal histology, the positive predictive value of local serum tTG-IgA increased when the serological threshold was defined at increasing multiples of the ULN (p<0·0001). The AUC for serum tTG-IgA for the prediction of duodenal villous atrophy was 0·87 (95% CI 0·81-0·92) when applying the categorical definition of serum tTG-IgA (positive [>1 × ULN] vs negative [≤1 × ULN]), and 0·93 (0·89-0·96) when applying the numerical definition of serum tTG-IgA (multiples of the ULN). Additional endoscopic findings included peptic gastritis (nine patients), autoimmune atrophic gastritis (three), reflux oesophagitis (31), gastric or duodenal ulcer (three), and Barrett's oesophagus (one). In the 1-year follow-up, a midgut ileum lymphoma was diagnosed in a woman on a gluten-free diet. INTERPRETATION: Our data showed that biopsy could be reasonably avoided in the diagnosis of coeliac disease in adults with reliable suspicion of coeliac disease and high serum tTG-IgA. FUNDING: None.
  • Erythematous capillary-lymphatic malformations mimicking blood vascular anomalies.

    Keeley, Vaughan; Riches, Katie
    Superficial erythematous cutaneous vascular malformations are assumed to be blood vascular in origin, but cutaneous lymphatic malformations can contain blood and appear red. Management may be different and so an accurate diagnosis is important. Cutaneous malformations were investigated through 2D histology and 3D whole-mount histology. Two lesions were clinically considered as port-wine birthmarks and another 3 lesions as erythematous telangiectasias. The aims were (i) to demonstrate that cutaneous erythematous malformations including telangiectasia can represent a lymphatic phenotype, (ii) to determine if lesions represent expanded but otherwise normal or malformed lymphatics, and (iii) to determine if the presence of erythrocytes explained the red color. Microscopy revealed all lesions as lymphatic structures. Port-wine birthmarks proved to be cystic lesions, with nonuniform lymphatic marker expression and a disconnected lymphatic network suggesting a lymphatic malformation. Erythematous telangiectasias represented expanded but nonmalformed lymphatics. Blood within lymphatics appeared to explain the color. Blood-lymphatic shunts could be detected in the erythematous telangiectasia. In conclusion, erythematous cutaneous capillary lesions may be lymphatic in origin but clinically indistinguishable from blood vascular malformations. Biopsy is advised for correct phenotyping and management. Erythrocytes are the likely explanation for color accessing lymphatics through lympho-venous shunts.
  • Intermittently scanned continuous glucose monitoring in adults with type 1 diabetes: A subgroup analysis from the FLASH-UK study.

    Wilmot, Emma
    BACKGROUND: The FLASH-UK trial showed lower HbA1c with intermittently-scanned continuous glucose monitoring (isCGM), as compared with self-monitoring of blood glucose (SMBG), in adults with type 1 diabetes and HbA1c ≥58 mmol/mol. (≥ 7.5%). Here we present results from the pre-specified subgroup analysis for the 24-week HbA1c (primary outcome) and selected sensor-based secondary outcomes. METHODS: This was a multicentre, parallel-design, randomised controlled trial. The difference in treatment effect between subgroups (baseline HbA1c (≤75 vs >75 mmol/mol (≤9.0 vs > 9.0%), treatment modality (pump vs injections), prior participation in structured education, age, educational level, impaired awareness of hypoglycaemia, deprivation index quintile sex, ethnic group, and Patient Health Questionnaire-9 (PHQ-9) detected depression category) were evaluated. RESULTS: One hundred fifty-six participants [females 44%, mean (SD) baseline HbA1c 71 (9) mmol/mol 8.6(0.8%), age 44 (15)] were randomly assigned, in a 1:1 ratio to isCGM (n=78) or SMBG (n=78). The mean (SD) baseline HbA1c (%) was 8.7 (0.9) in the isCGM group and 8.5 (0.8) in the SMBG group, lowering to 7.9 (0.8) vs 8.3 (0.9) respectively at 24 weeks (adjusted mean difference -0.5, 95% confidence interval[CI] -0.7 to -0.3; p<0.001]. For HbA1c, there was no impact of treatment modality, prior participation in structured education, deprivation index quintile, sex or baseline depression category. The between-group difference in HbA1c was larger for younger people [a reduction of 2.7 (95%CI 0.3 to 5.0; p=0.028) mmol/mol for every additional 15 years of age]. Those with HbA1c 76-97 mmol/mol (>9.0-11.0%) had a marginally non-significant higher reduction in HbA1c of 8.4 mmol/mol (3.3 to 13.5) compared to 3.1 (0.3 to 6.0) in those with HbA1c 58-75mmol/mol (p=0.08). For "Time in range" (% 3.9 to 10 mmol/l), the difference was larger for those with at least a bachelor's degree. For "Time below range" (% <3.9 mmol/l), the difference was larger for those using injections, older people, and those with less than bachelor's degree. CONCLUSIONS: Intermittently-scanned continuous glucose monitoring is generally effective across a range of baseline characteristics.
  • Renal medicine in the intensive care unit: a narrative review.

    Horne, Kerry; Selby, Nicholas
    Kidney disease, both acute and chronic, is commonly encountered on the intensive care unit. Due to the role the kidneys play in whole body homeostasis, it follows that their dysfunction has wide-ranging implications and can affect prescribing and therapeutic management. This narrative review discusses the pathophysiology of acute kidney injury and chronic kidney disease, and how this relates to critically unwell patients. We cover several aspects of the management of renal dysfunction on the critical care unit, exploring some of the recurrent themes within the literature, including type and timing of kidney replacement therapy, management of acute kidney injury, as well as discussing how novel biomarkers for acute kidney injury may help to identify patients suffering from acute kidney injury as well as risk stratifying these patients. We discuss how early involvement of specialist nephrology services can improve outcomes in patients with kidney disease as well as offer valuable diagnostic and specialist management advice, particularly for patients with established end stage kidney disease and patients who are already known to nephrology services. We also explore some of the ongoing research questions that need to be answered within this arena.
  • In severe alcohol-related hepatitis, acute kidney injury is prevalent, associated with mortality independent of liver disease severity, and can be predicted using IL-8 and micro-RNAs.

    Austin, Andrew
    BACKGROUND: The prevalence, prediction and impact of acute kidney injury (AKI) in alcohol-related hepatitis (AH) is uncertain. AIMS: We aimed to determine AKI incidence; association with mortality; evaluate serum biomarkers and the modifying effects of prednisolone and pentoxifylline in the largest AH cohort to date. METHODS: Participants in the Steroids or Pentoxifylline for Alcoholic Hepatitis trial with day zero (D0) creatinine available were included. AKI was defined by modified International Club of Ascites criteria; incident AKI as day 7 (D7) AKI without D0-AKI. Survival was compared by Kaplan-Meier; mortality associations by Cox regression; associations with AKI by binary logistic regression; biomarkers by AUROC analyses. RESULTS: D0-AKI was present in 198/1051 (19%) participants; incident AKI developed in a further 119/571 (21%) with available data. Participants with D0-AKI had higher 90-day mortality than those without (32% vs. 25%, p = 0.008), as did participants with incident AKI compared to those without D0-AKI or incident AKI (47% vs. 25%, p < 0.001). Incident AKI was associated with D90 mortality adjusted for age and discriminant function (AHR 2.15, 1.56-2.97, p < 0.001); D0-AKI was not. Prednisolone therapy reduced incident AKI (AOR 0.55, 0.36-0.85, p = 0.007) but not mortality. D0 bilirubin and IL-8 combined, miR-6826-5p, and miR-6811-3p predicted incident AKI (AUROCs 0.726, 0.821, 0.770, p < 0.01). CONCLUSIONS: Incident AKI is associated with 90-day mortality independent of liver function. Prednisolone therapy was associated with reduced incident AKI. IL-8 and several miRNAs are potential biomarkers to predict AKI. Novel therapies to prevent incident AKI should be evaluated in AH to reduce mortality.
  • Associations with age and glomerular filtration rate in a referred population with chronic kidney disease: Methods and baseline data from a UK multicentre cohort study (NURTuRE-CKD).

    Taal, Maarten; Lucas, Bethany
    BACKGROUND: Chronic kidney disease (CKD) is common but heterogenous and is associated with multiple adverse outcomes. The National Unified Renal Translational Research Enterprise (NURTuRE)-CKD cohort was established to investigate risk factors for clinically important outcomes in persons with CKD referred to secondary care. METHODS: Eligible participants with CKD stages G3-4 or stages G1-2 plus albuminuria > 30 mg/mmol were enrolled from 16 nephrology centres in England, Scotland and Wales from 2017 to 2019. Baseline assessment included demographic data, routine laboratory data and research samples. Clinical outcomes are being collected over 15 years by the UK Renal Registry using established data linkage. Baseline data are presented with subgroup analysis by age, sex and estimated GFR (eGFR). RESULTS: 2996 participants were enrolled. Median (interquartile range) age was 66 (54 to 74) years, 58.5% were male, eGFR 33.8 (24.0 to 46.6) ml/min/1.73m2 and UACR 209 (33 to 926) mg/g. 1883 participants (69.1%) were in high-risk CKD categories. Primary renal diagnosis was CKD of unknown cause in 32.3%, glomerular disease in 23.4% and diabetic kidney disease in 11.5%. Older participants and those with lower eGFR had higher systolic blood pressure and were less likely to be treated with renin-angiotensin system inhibitors (RASi) but were more likely to receive a statin. Female participants were less likely to receive a RASi or statin. CONCLUSIONS: NURTuRE-CKD is a prospective cohort of persons who are at relatively high risk of adverse outcomes. Long-term follow-up and a large biorepository create opportunities for research to improve risk prediction and investigate underlying mechanisms to inform new treatment development.
  • Exploring the variability of sarcopenia prevalence in a research population using different disease definitions.

    Willott, Ruth; Gordon, Adam L
    BACKGROUND: Sarcopenia is the progressive loss of muscle mass and function with age. A number of different sarcopenia definitions have been proposed and utilised in research. This study aimed to investigate how the prevalence of sarcopenia in a research cohort of older adults is influenced by the use of independent aspects of these different definitions. METHODS: Data from 255 research participants were compiled. Defining criteria by the European Working Group on Sarcopenia in Older People, the International Working Group on Sarcopenia (IWGS), and the Foundation for the National Institutes of Health were applied. RESULTS: Prevalence of sarcopenia using muscle mass ranged from 4 to 22%. Gait speed and handgrip strength criteria identified 4-34% and 4-16% of participants as sarcopenic, respectively. CONCLUSION: Prevalence of sarcopenia differs substantially depending on the criteria used. Work is required to address the impact of this for sarcopenia research to be usefully translated to inform on clinical practice.
  • Blood pressure targets in chronic kidney disease: still no consensus.

    Taal, Maarten; Lucas, Bethany
    PURPOSE OF REVIEW: Despite a strong consensus that treatment of hypertension is fundamental to strategies seeking to slow chronic kidney disease (CKD) progression and reduce the associated risk of cardiovascular events (CVE), controversy persists regarding optimal blood pressure (BP) targets. This article reviews the evidence for different targets, discusses associated controversies and suggests approaches to improve BP control. RECENT FINDINGS: Landmark clinical trials established the principle that lower BP targets are associated with slower progression of CKD in people with a greater magnitude of proteinuria and previous guidelines recommended a target BP of <130/80 mmHg for those with proteinuria. However, the Systolic Blood Pressure Intervention Trial provided new evidence that a systolic BP target of <120 mmHg was associated with a reduced risk of CVE, though there was no impact on CKD progression and there was concern about an increase in renal adverse events. Nevertheless, 2021 Kidney Disease Improving Global Outcomes guidelines recommended systolic BP <120 mmHg, though other updated guidelines did not follow this trend. All guidelines emphasise the importance of standardised BP measurement and a personalised approach. SUMMARY: An individualised and shared decision-making approach to BP target setting and management is recommended, guided by standardised BP measurement.
  • Estimating the cost effectiveness of intermittently scanned continuous glucose monitoring in adults with type 1 diabetes in England.

    Wilmot, Emma
    OBJECTIVE: We previously showed that intermittently scanned continuous glucose monitoring (isCGM) reduces HbA1c at 24 weeks compared with self-monitoring of blood glucose with finger pricking (SMBG) in adults with type 1 diabetes and high HbA1c levels (58 to 97 mmol/mol [7.5-11%]). We aim to assess the economic impact of isCGM compared with SMBG. METHODS: Participant-level baseline and follow-up health status (EQ-5D-5L) and within-trial healthcare resource-use data were collected. Quality-adjusted life-years (QALYs) were derived at 24 weeks, adjusting for baseline EQ-5D-5L. Participant-level costs were generated. Using the IQVIA CORE Diabetes Model, economic analysis was performed from the National Health Service perspective over a lifetime horizon, discounted at 3.5%. RESULTS: Within-trial EQ-5D-5L showed non-significant adjusted incremental QALY gain of 0.006 (95%CI: -0.007 to 0.019) for isCGM compared with SMBG and an adjusted cost increase of £548 (95%CI: 381 to 714) per participant. The lifetime projected incremental cost (95%CI) of isCGM was £1,954 (-5,108 to 8,904) with an incremental QALY (95%CI) gain of 0.436 (0.195 to 0.652) resulting in an incremental cost-per-QALY of £4,477. In all subgroups, isCGM had an incremental cost-per-QALY better than £20,000 compared with SMBG; for people with baseline HbA1c >75 mmol/mol (9.0%), it was cost-saving. Sensitivity analysis suggested isCGM remains cost-effective if its effectiveness lasts for at least 7 years. CONCLUSION: While isCGM is associated with increased short-term costs, compared with SMBG, its benefits in lowering HbA1c will lead to sufficient long-term health-gains and cost-savings to justify costs, so long as the effect lasts into the medium term.
  • Intrinsic Motivation

    McNaughton, Harry
    The prevailing wisdom in neurological rehabilitation, and particularly for stroke, is that physical therapies are the key to improvements in function. Despite accepting the importance of 'the motivated patient', the lack of simple, proven ways to improve intrinsic motivation has hindered efforts to combine physical therapies with motivation. Now there is available a simple, free, well-validated approach to encourage intrinsic motivation ('Take Charge'). The benefits for people who had a stroke are well-established but this could be applied to people with a range of neurological and other disorders. We provide the evidential support for this approach and suggest ways of incorporating it into daily practice.
  • No-biopsy diagnostic approach to coeliac disease.

    Holmes, Geoffrey
    This brief review outlines contributions that Michael Marsh and others made to understanding the structure and function of the upper small bowel mucosa and the formation of abnormalities that occur in coeliac disease (CD). He introduced his classification of lesions 30 years ago that has been widely adopted. The development and use of serological tests to screen for and diagnose CD in children and adults without the need for a small bowel biopsy in a considerable proportion is also recognised and will gain traction.
  • Delivering manual cardiopulmonary resuscitation (CPR) in a diving bell: an analysis of head-to-chest and knee-to-chest compression techniques.

    Johnson, Graham; Tilbury, Nicholas; Hughes, Gareth; Tabner, Andrew
    INTRODUCTION: Chest compression often cannot be administered using conventional techniques in a diving bell. Multiple alternative techniques are taught, including head-to-chest and both prone and seated knee-to-chest compressions, but there are no supporting efficacy data. This study evaluated the efficacy, safety and sustainability of these techniques. METHODS: Chest compressions were delivered by a team of expert cardiopulmonary resuscitation (CPR) providers. The primary outcome was proportion of chest compressions delivered to target depth compared to conventional CPR. Techniques found to be safe and potentially effective by the study team were further trialled by 20 emergency department staff members. RESULTS: Expert providers delivered a median of 98% (interquartile range [IQR] 1.5%) of chest compressions to the target depth using conventional CPR. Only 32% (IQR 60.8%) of head-to-chest compressions were delivered to depth; evaluation of the technique was abandoned due to adverse effects. No study team member could register sustained compression outputs using prone knee-to-chest compressions. Seated knee-to-chest were delivered to depth 12% (IQR 49%) of the time; some compression providers delivered > 90% of compressions to depth. CONCLUSIONS: Head-to-chest compressions have limited efficacy and cause harm to providers; they should not be taught or used. Prone knee-to-chest compressions are ineffective. Seated knee-to-chest compressions have poor overall efficacy but some providers deliver them well. Further research is required to establish whether this technique is feasible, effective and sustainable in a diving bell setting, and whether it can be taught and improved with practise.
  • An evaluation of the NUI Compact Chest Compression Device (NCCD), a mechanical CPR device suitable for use in the saturation diving environment.

    Tabner, Andrew
    INTRODUCTION: Provision of manual chest compressions in a diving bell using a conventional technique is often impossible, and alternative techniques are poorly evidenced in terms of efficacy and sustainability. The first mechanical cardiopulmonary resuscitation (CPR) device suitable for use in this environment, the NUI Compact Chest Compression Device (NCCD), has recently been designed and manufactured. This study assessed both the efficacy of the device in delivering chest compressions to both prone and seated manikins, and the ability of novice users to apply and operate it. METHODS: Compression efficacy was assessed using a Resusi Anne QCPR intelligent manikin, and the primary outcome was the proportion of compressions delivered to target depth (50-60 mm). The gold standard was that achieved by expert CPR providers delivering manual CPR; the LUCAS 3 mCPR device was a further comparator. RESULTS: The NCCD delivered 100% of compressions to target depth compared to 98% for the gold standard (interquartile range 1.5%) and 98% for the LUCAS 3 when applied to both supine and seated manikins. The NCCD sometimes became dislodged and had to be reapplied when used with a seated manikin. CONCLUSIONS: The NCCD can deliver chest compressions at target rate and depth to both supine and seated manikins with efficacy equivalent to manual CPR and the LUCAS 3. It can become dislodged when applied to a seated manikin; its design has now been altered to prevent this. New users can be trained in use of the NCCD quickly, but practise is required to ensure effective use.
  • Digital health and acute kidney injury: consensus report of the 27th Acute Disease Quality Initiative workgroup.

    Selby, Nicholas
    Acute kidney injury (AKI), which is a common complication of acute illnesses, affects the health of individuals in community, acute care and post-acute care settings. Although the recognition, prevention and management of AKI has advanced over the past decades, its incidence and related morbidity, mortality and health care burden remain overwhelming. The rapid growth of digital technologies has provided a new platform to improve patient care, and reports show demonstrable benefits in care processes and, in some instances, in patient outcomes. However, despite great progress, the potential benefits of using digital technology to manage AKI has not yet been fully explored or implemented in clinical practice. Digital health studies in AKI have shown variable evidence of benefits, and the digital divide means that access to digital technologies is not equitable. Upstream research and development costs, limited stakeholder participation and acceptance, and poor scalability of digital health solutions have hindered their widespread implementation and use. Here, we provide recommendations from the Acute Disease Quality Initiative consensus meeting, which involved experts in adult and paediatric nephrology, critical care, pharmacy and data science, at which the use of digital health for risk prediction, prevention, identification and management of AKI and its consequences was discussed.
  • What is the significance of a faecal elastase-1 level between 200 and 500μg/g?

    Mathew, A; Mathew
    BACKGROUND: Pancreatic exocrine insufficiency is a cause of malabsorption. It is generally diagnosed if faecal elastase-1 (FE-1) levels are below 200 µg/g. Pancreatic function is assumed to be normal when faecal elastase levels are >500 µg/g. The significance of faecal elastase levels above 200 µg/g but less than 500 µg/g is unclear. METHODS: This retrospective study reports the response to treatment in patients who had an FE-1 level between 200 and 500 µg/g. RESULTS: Of these 82 patients, 28 were offered pancreatic enzyme replacement therapy (PERT). A clinical response, defined as an improvement in their initial symptoms after commencing PERT, was seen in 20 patients (71%), 7 with potentially predisposing conditions and 13 with functional diarrhoea. PERT particularly abolished or improved diarrhoea, steatorrhoea and flatulence. CONCLUSION: Clinicians should, therefore, be aware that a trial of PERT given to patients with FE-1 levels between 200 and 500 µg/g may lead to improvement in gastrointestinal symptoms.
  • The use of non-invasive brain stimulation techniques to reduce body weight and food cravings: A systematic review and meta-analysis.

    Al-Khyatt, Waleed; Alhindi, Y A; Idris, Iskandar
    Several studies demonstrated non-invasive brain stimulation (NIBS) techniques such as transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) are safe and simple techniques that can reduce body weight, food cravings, and food consumption in patients with obesity. However, a systematic to evaluate the efficacy of active NIBS versus sham stimulation in reducing body weight and food cravings in patients with obesity is not available. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) using PubMed, Embase, MEDLINE, and Cochrane Central Register of Control Trial between January 1990 and February 2022. Mean differences (MDs) for continuous outcome variables with 95% confidence intervals (95% CIs) were used to examine the effects of NIBS on body weight and body mass index (BMI), whereas the hedges's g test was used to measure the effects on food craving. Nineteen RCTs involving 571 participants were included in this study. Active neurostimulation (TMS and tDCS) was significantly more likely than sham stimulation to reduce body weight (TMS: -3.29 kg, 95% CI [-5.32, -1.26]; I2  = 48%; p < .001; tDCS: -0.82 kg, 95% CI [-1.01, -0.62]; I2  = 0.0%; p = .00) and BMI (TMS: -0.74, 95% CI [-1.17, -0.31]; I2  = 0% p = .00; tDCS: MD = -0.55, 95% CI [-2.32, 1.21]; I2  = 0% p = .54) as well as food cravings (TMS: g = -0.91, 95% CI [-1.68, -0.14]; I2  = 88 p = .00; tDCS: g = -0.32, 95% CI [-0.62, -0.02]; p = .04). Compared with sham stimulation, our findings indicate that active NIBS can significantly help to reduce body weight and food cravings. Hence, these novel techniques may be used as primary or adjunct tools in treating patients with obesity.
  • Impact of diabetes on remodelling, microvascular function and exercise capacity in aortic stenosis.

    Kelly, Damien
    OBJECTIVE: To characterise cardiac remodelling, exercise capacity and fibroinflammatory biomarkers in patients with aortic stenosis (AS) with and without diabetes, and assess the impact of diabetes on outcomes. METHODS: Patients with moderate or severe AS with and without diabetes underwent echocardiography, stress cardiovascular magnetic resonance (CMR), cardiopulmonary exercise testing and plasma biomarker analysis. Primary endpoint for survival analysis was a composite of cardiovascular mortality, myocardial infarction, hospitalisation with heart failure, syncope or arrhythmia. Secondary endpoint was all-cause death. RESULTS: Diabetes (n=56) and non-diabetes groups (n=198) were well matched for age, sex, ethnicity, blood pressure and severity of AS. The diabetes group had higher body mass index, lower estimated glomerular filtration rate and higher rates of hypertension, hyperlipidaemia and symptoms of AS. Biventricular volumes and systolic function were similar, but the diabetes group had higher extracellular volume fraction (25.9%±3.1% vs 24.8%±2.4%, p=0.020), lower myocardial perfusion reserve (2.02±0.75 vs 2.34±0.68, p=0.046) and lower percentage predicted peak oxygen consumption (68%±21% vs 77%±17%, p=0.002) compared with the non-diabetes group. Higher levels of renin (log10renin: 3.27±0.59 vs 2.82±0.69 pg/mL, p<0.001) were found in diabetes. Multivariable Cox regression analysis showed diabetes was not associated with cardiovascular outcomes, but was independently associated with all-cause mortality (HR 2.04, 95% CI 1.05 to 4.00; p=0.037). CONCLUSIONS: In patients with moderate-to-severe AS, diabetes is associated with reduced exercise capacity, increased diffuse myocardial fibrosis and microvascular dysfunction, but not cardiovascular events despite a small increase in mortality.
  • Peri- and Postoperative Outcomes for Obstructive Sleep Apnoea Patients after Bariatric Surgery-a Systematic Review and Meta-analysis.

    Holt, G; Al-Khyatt, Waleed; Idris, Iskandar
    BACKGROUND: Obstructive sleep apnoea (OSA) is prevalent among patients undergoing bariatric surgery. Previous studies have reported a higher risk of complications, ICU admission and longer length of stay in patients with OSA following surgery. However, clinical outcomes following bariatric surgery are unclear. The hypothesis is that patients with OSA will have an increased risk of these outcome measures after bariatric surgery. METHODS: A systematic review and meta-analysis were performed to answer the research question. Searches for bariatric surgery and obstructive sleep apnoea were performed using PubMed and Ovid Medline. Studies which compared OSA and non-OSA patients undergoing bariatric surgery and used outcome measures that included length of stay, risk of complications, 30-day readmission and need for ICU admission were selected for the systematic review. Comparable datasets from these studies were used for the meta-analysis. RESULTS: Patients with OSA are at greater risk of complications after bariatric surgery (RR = 1.23 [CI: 1.01, 1.5], P = 0.04), driven mostly by an increased risk of cardiac complications (RR = 2.44 [CI: 1.26, 4.76], P = 0.009). There were no significant differences between the OSA and non-OSA cohorts in the other outcome variables (respiratory complications, length of stay, 30-day readmission and need for ICU admission). CONCLUSION: Following bariatric surgery, patients with OSA must be managed carefully due to the increased risk of cardiac complications. However, patients with OSA are not more likely to require a longer length of stay or readmission.

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