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Background: Inhibitors of the renin-angiotensin-aldosterone system (RAAS), such as ACE inhibitors (ACEi), angiotensin-II receptor blockers and mineralocorticoid receptor antagonists, reduce morbidity and mortality in hypertension, congestive heart failure and chronic kidney disease. However, their use can lead to hyperkalaemia. We examined the proportions of RAAS inhibitor (RAASi) reduction or withdrawal, across GFR strata, following hospitalisation and the effect on patient mortality., Methods: This was a retrospective cohort study of adult patients hospitalised from 1 January2017 to 31 December2020. Biochemistry data, clinical notes and medicines use were extracted using the CogStack platform, from electronic health records. Patients were identified by creatinine measurement during hospitalisation. Hyperkalaemia was defined as potassium > 5.0 mmol/L, with severity categorisation. RAASi discontinuation defined as ≥ 48 h without administration. Mortality risk associated with RAASi cessation was assessed using Cox proportional hazards models., Results: Among 129,172 patients with potassium measurements, 49,011 were hospitalised. Hyperkalaemia prevalence was 8.57% in the emergency department and 16.79% among hospitalised patients. Higher hyperkalaemia levels correlated with increased CKD and heart failure. RAASi use was more common in hyperkalaemic patients, with higher discontinuation rates during hospitalisation (36% with potassium 5-5.5 mmol/L; 61% with potassium > 6.5 mmol/L). By discharge, 32% of patients had RAASi stopped, and 2% doses reduced. Discontinuation of RAASi was associated with 37% worse survival probability., Conclusion: RAASi cessation was greater with hyperkalaemia and associated with increased mortality in hospitalised patients. Reinstitution of RAASi after hospital discharge, or alternative management of hyperkalaemia if maintained on RAASi therapy, may improve clinical outcomes., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: The King’s College Hospital Research and Innovation Department, after review of the project, considered this as a service evaluation, rather than research. We confirmed this opinion using the HRA ‘Is this research?’ decision tool ( http://www.hra-decisiontools.org.uk/research/ ). We used anonymous data, at scale, at source (within the hospital IT system), and therefore, patient-level consent was not required. Approval for this approach to use of CogStack is within London—South East Research Ethics Committee approval (18/LO/2048) 2nd January 2019. King's Electronic Patient Record Interface (KERRI) committee (project ID 20210405A) approved the project (within the boundaries of CogStack ethical approval 18/LO/2048) on 7th May 2021. Consent to publish: Not applicable., (© 2024. The Author(s).)

Black African-Caribbean (BAC) populations are at greater risk of cardiometabolic disease than White Europeans (WE), despite exhibiting lower fasting triacylglycerol (TAG) concentrations. However, limited data exist regarding postprandial fatty acid metabolism in BAC populations. This study determined the ethnic differences in postprandial fatty acid metabolism between overweight and obese WE and BAC men. WE [ n = 10, age 33.3 ± 1.7 yr; body mass index (BMI) = 26.8 (25.8-31.0) kg/m 2 ] and BAC [ n = 9, age 27.9 ± 1.0 yr; BMI = 27.5 (26.0-28.6) kg/m 2 ] men consumed two consecutive (at 0 and 300 min) moderate-to-high-fat meals-the first labeled with [U- 13 C]palmitate. The plasma concentration and appearance of meal-derived fatty acids in very-low-density lipoprotein (VLDL)-TAG, chylomicron-TAG, and nonesterified fatty acid (NEFA) were determined over an 8-h postprandial period. Indirect calorimetry with 13 CO 2 enrichment determined total and meal-derived fatty acid oxidation rates, and plasma β-hydroxybutyrate (3-OHB) concentration was measured to assess ketogenesis. BAC exhibited lower postprandial TAG [area under the curve (AUC 0-480 ) = 671 (563-802) vs. 469 (354-623) mmol/L/min, P = 0.022] and VLDL-TAG [AUC 0-480 = 288 ± 30 vs. 145 ± 27 mmol/L/min, P = 0.003] concentrations than WE. The appearance of meal-derived fatty acids in VLDL-TAG was lower in BAC than in WE (AUC 0-480 = 133 ± 12 vs. 78 ± 13 mmol/L/min, P = 0.007). Following the second meal, BAC showed a trend for lower chylomicron-TAG concentration [AUC 300-480 = 69 (51-93) vs. 43 (28-67) mmol/L/min, P = 0.057]. There were no ethnic differences in the appearance of chylomicron-TAG, cumulative fatty acid oxidation, and the NEFA:3-OHB ratio ( P > 0.05). In conclusion, BAC exhibit lower postprandial TAG concentrations compared with WE men, driven by lower VLDL-TAG concentrations and possibly lower chylomicron-TAG in the late postprandial period. These findings suggest that postprandial fatty acid trafficking may be a less important determinant of cardiometabolic risk in BAC than in WE men. NEW & NOTEWORTHY Postprandial TAG is lower in Black African-Caribbean men than in White European men, and this is likely driven by lower meal-derived VLDL-TAG in Black African-Caribbean men. This observation could suggest that fatty acid trafficking may be a less important determinant of cardiometabolic risk in Black Africans than in White European men.

Competing Interests: There are no conflicts of interest.

Background: Timely and economic provision of revascularisation procedures is a major healthcare need. We aimed to examine the safety and efficacy of daycase-based lower extremity endovascular revascularisation procedures in patients with peripheral artery disease., Methods: In this systematic review and meta-analysis, we searched MEDLINE and Embase for studies from Jan 01, 2000 through Apr 01, 2024 reporting complications of lower limb endovascular revascularisation procedures with same-day discharge. Eligibility-criteria, complications, and patient characteristics were extracted, methodological quality assessed (adapted Newcastle-Ottawa Scale), and meta-analyses of complications and technical success performed to provide pooled estimates. This study is registered with PROSPERO, CRD42022316466., Findings: Thirty observational studies (17 retrospective, 13 prospective) and 1 RCT reported 2427 minor and 653 major complications after 99,600 daycase procedures (93,344 patients). Eighteen studies reported daycase eligibility-criteria including 'responsible adult companion' (78%), 'proximity to hospital', and 'telephone availability' and excluding unstable and severe co-morbidities, offset coagulation, and severe chronic kidney disease. Pooled incidences of minor (4.7% [95% CI 3.8-5.6%], I 2  = 96%) and major (0.64% [95% CI 0.48-0.79%], I 2  = 46%) complications were low and technical success high (93% [95% CI 91-96%], I 2  = 97%). Most complications were related to the puncture site. Pooled conversion-to-hospitalisation rates and re-admission after discharge were 1.6% (95% CI 1.1-2.2%, I 2  = 82%) and 0.11% (95% CI 0.095-0.23%, I 2  = 97%), respectively. Meta-regression identified that minor complications decreased since 2000. Male sex and coronary artery disease were associated with more frequent, and higher age and closure device use with less minor complications. Diabetes mellitus and chronic kidney disease were associated with less major complications. Six studies reported complication rates both in daycases and inpatients and there was no significant difference (-0.8% [95% CI -1.9 to 0.3%])., Interpretation: After careful evaluation of eligibility, lower limb angioplasty can be performed safely with high technical success in a daycase setting. Most complications arise from the puncture site and not the procedure itself highlighting the importance of optimal access site management. The heterogeneity between studies warrants standardised monitoring of complications and outcomes., Funding: European Partnership on Metrology, co-financed from European Union's Horizon Europe Research and Innovation Programme and UK Research and Innovation, and Medical Research Council., Competing Interests: CH, JM and VB are members of the board of the European Society of Vascular Medicine. CH and OS are members of the nucleus of the European Society of Cardiology Working Group on Aorta and Peripheral Vascular Disease (CH treasurer and chairperson-elect, OS current chairperson). CH has received research funding from the European Partnership on Metrology, co-financed from European Union’s Horizon Europe Research and Innovation Programme and UK Research and Innovation, and Medical Research Council and honoraria for lectures by Bayer not related to the manuscript. CH declares being a council member and president-elect of Royal Society of Medicine, Vascular Medicine Council. All other authors declare no competing interests., (© 2024 The Author(s).)

Hyperkalaemia is associated with prolonged hospital admission and worse mortality. Hyperkalaemia may also necessitate clinical consults, therapies for hyperkalaemia and high-dependency bed utilisation. We evaluated the 'hidden' human and organisational resource utilisation for hyperkalaemia in hospitalised patients. This was a single-centre, observational cohort study (Jan 2017-Dec 2020) at a tertiary-care hospital. The CogStack system (data processing and analytics platform) was used to search unstructured and structured data from individual patient records. Association between potassium and death was modelled using cubic spline regression, adjusted for age, sex, and comorbidities. Cox proportional hazards estimated the hazard of death compared with normokalaemia (3.5-5.0 mmol/l). 129,172 patients had potassium measurements in the emergency department. Incidence of hyperkalaemia was 85.7 per 1000. There were 49,011 emergency admissions. Potassium > 6.5 mmol/L had 3.9-fold worse in-hospital mortality than normokalaemia. Chronic kidney disease was present in 21% with potassium 5-5.5 mmol/L and 54% with potassium > 6.5 mmol/L. For diabetes, it was 20% and 32%, respectively. Of those with potassium > 6.5 mmol/L, 29% had nephrology review, and 13% critical care review; in this group 22% transferred to renal wards and 8% to the critical care unit. Dialysis was used in 39% of those with peak potassium > 6.5 mmol/L. Admission hyperkalaemia and hypokalaemia were independently associated with reduced likelihood of hospital discharge. Hyperkalaemia is associated with greater in-hospital mortality and reduced likelihood of hospital discharge. It necessitated significant utilisation of nephrology and critical care consultations and greater likelihood of patient transfer to renal and critical care., (© 2024. The Author(s).)

Background: Ankle brachial pressure index can be estimated (eABPI) using cuffless ankle Doppler ultrasound. We evaluated the prognostic value of eABPI measured during pre- and post-procedural ultrasound exams to predict the clinical outcome after endovascular revascularisations., Methods: In this prospective, single-centre, service evaluation, consecutive patients with symptomatic peripheral artery disease undergoing lower limb endovascular revascularisations between July, 26 2018 and January, 13 2022 at Surrey and Sussex Healthcare NHS Trust (Redhill, UK) were analysed. eABPI was determined using the higher acceleration index measured with angle-corrected duplex ultrasound in ankle arteries before and ≤1 month post-procedure. Clinical outcomes (mortality, major amputations, amputation-free survival [AFS], clinically driven target lesion revascularization [cdTLR], major adverse limb events [MALE; cdTLR and major amputation], wound healing) were assessed over 1 year., Findings: Of 246 patients treated, for 219 patients (median 75 [IQR 66-83] years) pre- and post-procedural eABPI (0.50 [0.33-0.59] and 0.90 [0.69-1.0], p  < 0.0001) were available, respectively. In n = 199 patients with chronic limb-threatening ischaemia (CLTI) Kaplan-Meier survival analyses showed that higher post-procedural, but not pre-procedural, eABPI was associated with favourable AFS, MALE, cdTLR, and wound healing. This was confirmed in Cox regression analysis and remained significant with adjustment for pre-procedural eABPI, age, sex, co-morbidities, treated levels, wound score, and foot infection. Whereas all clinical outcomes, except for survival, were significantly better at ≥0.7 vs  <0.7, wound healing (unadjusted: HR 1.7 (95% CI 1.2-2.6), adjusted: HR 2.1 (95% CI 1.3-3.1), cdTLR, and MALE (unadjusted: HR 0.41 (95% CI 0.18-0.93), adjusted: HR 0.28 (95% CI 0.11-0.74) were significantly improved at ≥0.9 vs  <0.9., Interpretation: Post-procedural eABPI can provide valid, clinically important prognostic and predictive information. Our data indicate that revascularisations should target values of at least 0.9 to achieve optimal outcomes. Future studies need to confirm generalisability and cost-effectiveness in a wider context., Funding: European Partnership on Metrology, co-financed from European Union's Horizon Europe Research and Innovation Programme and UK Research and Innovation., Competing Interests: CH has received honoraria for presentations by Bayer and is member of the board of European Society of Vascular Medicine and board of the European Society of Cardiology Working Group on Aorta and Peripheral Vascular Disease and member of the Royal Society of Medicine Vascular, Lipid and Metabolic Medicine Council. All other authors declare no competing interests., (© 2023 The Author(s).)

In the UK, populations of Black African and Caribbean (BAC) ethnicity suffer higher rates of cardiometabolic disease than White Europeans (WE). Obesity, leading to increased visceral adipose tissue (VAT) and intrahepatic lipid (IHL), has long been associated with cardiometabolic risk, driving insulin resistance and defective fatty acid/lipoprotein metabolism. These defects are compounded by a state of chronic low-grade inflammation, driven by dysfunctional adipose tissue. Emerging evidence has highlighted associations between central complement system components and adipose tissue, fatty acid metabolism and inflammation; it may therefore sit at the intersection of various cardiometabolic disease risk factors. However, increasing evidence suggests an ethnic divergence in pathophysiology, whereby current theories fail to explain the high rates of cardiometabolic disease in BAC populations. Lower fasting and postprandial TAG has been reported in BAC, alongside lower VAT and IHL deposition, which are paradoxical to the high rates of cardiometabolic disease exhibited by this ethnic group. Furthermore, BAC have been shown to exhibit a more anti-inflammatory profile, with lower TNF-α and greater IL-10. In contrast, recent evidence has revealed greater complement activation in BAC compared to WE, suggesting its dysregulation may play a greater role in the high rates of cardiometabolic disease experienced by this population. This review outlines the current theories of how obesity is proposed to drive cardiometabolic disease, before discussing evidence for ethnic differences in disease pathophysiology between BAC and WE populations.

Aim: To quantify the impact of foot complications on mortality outcomes in people with type 2 diabetes (T2D), and how routinely measured factors might modulate that risk., Materials and Methods: Data for individuals with T2D for 2010-2020, from the Salford Integrated Care Record (Salford, UK), were extracted for laboratory and clinical data, and deaths. Annual expected deaths were taken from Office of National Statistics mortality data. An index of multiple deprivation (IMD) adjusted the standardized mortality ratio (SMR&#95;IMD). Life years lost per death (LYLD) was estimated from the difference between expected and actual deaths., Results: A total of 11 806 T2D patients were included, with 5583 new diagnoses and 3921 deaths during 2010-2020. The number of expected deaths was 2135; after IMD adjustment, there were 2595 expected deaths. Therefore, excess deaths numbered 1326 (SMR&#95;IMD 1.51). No foot complications were evident in n = 9857. This group had an SMR&#95;IMD of 1.13 and 2.74 LYLD. In total, 2979 patients had any foot complication recorded. In this group, the SMD&#95;IMR was 2.29; of these, 2555 (75%) had only one foot complication. Patients with a foot complication showed little difference in percentage HbA1c more than 58 mmol/mol. In multivariate analysis, for those with a foot complication and an albumin-to-creatinine ratio of more than 3 mg/mmol, the odds ratio (OR) for death was 1.93, and for an estimated glomerular filtration rate of less than 60 mL/min/1.73m 2 , the OR for death was 1.92., Conclusions: Patients with T2D but without a foot complication have an SMR&#95;IMD that is only slightly higher than that of the general population. Those diagnosed with a foot complication have a mortality risk that is double that of those without T2D., (© 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Introduction: The standardised mortality rate (SMR) for people with diabetes in England is 1.5-1.7, with differences in outcomes between sexes. There has been little work examining the factors that could have an impact on this or on what may determine sex differences in outcome., Methods: Data were extracted for patients with type 2 diabetes (T2D) in Salford (England) in 2010 for the years up to 2020, including any deaths recorded. Expected deaths were calculated from annual Office of National Statistics mortality rate and life expectancy by age and gender, adjusted for the local Index of Multiple Deprivation (IMD). This provided the SMR deprivation (SMRd), and life expectancy years lost per death (LEYLD). The effects of treatment type, and clinical features on SMRd relative to sex were examined by univariable and multivariable analysis., Results: Data from n = 11,806 (F = 5184; M = 6622) patients were included. Of these, n = 5540 were newly diagnosed and n = 3921 died (F = 1841; M = 2080). In total, n = 78,930 patient years. The expected deaths numbered n = 2596 (adjusted for age, sex, and IMD). Excess deaths were n = 1325 (F = 689; M = 636). Life expectancy years lost (LEYL) 18,989 (F = 9714; M = 9275). SMRd 1.51 (F = 1.60; M = 1.44) and LEYLD 4.84 years (F = 5.28; M = 4.46). The impact of risk factors was not different by sex. However, women had higher prevalence of % diagnosed >65 years of age; % last eGFR <60 mLs/min/1.73 m 2 , and lower prevalence of % prescribed ACE-inhibitor/ARB, DPP4-inhibitor and SGLT2-inhibitor. Applying the male prevalence rate to the female population and expected mortality suggested n = 437 (55%) of excess T2D female deaths were attributed to sex difference in the prevalence of these risk and protective factors., Conclusions: Outcomes in women with T2DM are worse than in men, contributed to by greater prevalence of adverse factors and less prescribing of cardioprotective medication., (© 2023 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.)

We evaluated the impact of COVID-19 restriction on the angioplasty service and outcome of chronic limb-threatening ischaemia (CLTI) patients undergoing lower-limb angioplasty in a UK secondary care setting. Consecutive patients were analysed retrospectively. Pre-COVID-19 (08/2018-02/2020), 106 CLTI patients (91% Fontaine 4; 60% diabetes mellitus) and during COVID-19 (03/2020-07/2021) 94 patients were treated (86% Fontaine 4; 66% diabetes mellitus). While the average monthly number of patients treated did not change, the proportion of day cases significantly increased (53% to 80%), and hospitalised patients decreased. Patients treated in ≤14/5 days after referral significantly increased to 64/63%. Kaplan-Meier survival analysis (30-day/1-year) showed that neither wound healing nor mortality were significantly changed during COVID-19. In day cases, 1-year but not 30-day major amputations significantly increased, and clinically driven target-lesion revascularisation decreased during COVID-19. One-year mortality was significantly worse in hospitalised compared to day cases (14% vs. 43%) at similar wound healing rates (83% vs. 84%). The most frequent known cause of death was infectious disease (64%), while cardiovascular (21%) was less frequent. Despite COVID-19 restrictions, a safe and effective angioplasty service was maintained while shortening waiting times. Very high mortality rates in hospitalised patients may indicate that CLTI patients need to be referred and treated more aggressively earlier.

Objectives: Perioperative nutrition aims to replenish nutritional stores before surgery and reduce postoperative complications. 'Immunonutrition' (including omega-3 fatty acids) may modulate the immune system and attenuate the postoperative inflammatory response. Hitherto, immunonutrition has overwhelmingly been administered in the postoperative period-however, this may be too late to provide benefit., Design: A systematic literature search using MEDLINE and EMBASE for randomized controlled trials (RCTs)., Setting: Perioperative major gastrointestinal surgery., Participants: Patients undergoing major gastrointestinal surgery., Interventions: Omega-3 fatty acid supplementation commenced in the preoperative period, with or without continuation into postoperative period., Main Outcome Measures: The effect of preoperative omega-3 fatty acids on inflammatory response and clinical outcomes., Results: 833 studies were identified. After applying inclusion and exclusion criteria, 12 RCTs, involving 1456 randomized patients, were included. Ten articles exclusively enrolled patients with cancer. Seven studies used a combination of EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) as the intervention and five studies used EPA alone. Eight out of 12 studies continued preoperative nutritional support into the postoperative period.Of the nine studies reporting mortality, no difference was seen. Duration of hospitalisation ranged from 4.5 to 18 days with intervention and 3.5 to 23.5 days with control. Omega-3 fatty acids had no effect on postoperative C-reactive protein and the effect on cytokines (including tumor necrosis factor-α, interleukin (IL)-6 and IL-10) was inconsistent. Ten of the 12 studies had low risk of bias, with one study having moderate bias from allocation and blinding., Conclusions: There is insufficient evidence to support routine preoperative omega-3 fatty acid supplementation for major gastrointestinal surgery, even when this is continued after surgery., Prospero Registration Number: CRD42018108333., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Delayed wound healing is a devastating complication of diabetes and supplementation with fish oil, a source of anti-inflammatory omega-3 (ω-3) fatty acids including eicosapentaenoic acid (EPA), seems an appealing treatment strategy. However, some studies have shown that ω-3 fatty acids may have a deleterious effect on skin repair and the effects of oral administration of EPA on wound healing in diabetes are unclear. We used streptozotocin-induced diabetes as a mouse model to investigate the effects of oral administration of an EPA-rich oil on wound closure and quality of new tissue formed. Gas chromatography analysis of serum and skin showed that EPA-rich oil increased the incorporation of ω-3 and decreased ω-6 fatty acids, resulting in reduction of the ω-6/ω-3 ratio. On the tenth day after wounding, EPA increased production of IL-10 by neutrophils in the wound, reduced collagen deposition, and ultimately delayed wound closure and impaired quality of the healed tissue. This effect was PPAR-γ-dependent. EPA and IL-10 reduced collagen production by fibroblasts in vitro . In vivo , topical PPAR-γ-blockade reversed the deleterious effects of EPA on wound closure and on collagen organization in diabetic mice. We also observed a reduction in IL-10 production by neutrophils in diabetic mice treated topically with the PPAR-γ blocker. These results show that oral supplementation with EPA-rich oil impairs skin wound healing in diabetes, acting on inflammatory and non-inflammatory cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Burger, Sagiorato, Silva, Candreva, Pacheco, White, Castelucci, Pral, Fisk, Rabelo, Elias-Oliveira, Osório, Consonni, Farias, Vinolo, Lameu, Carlos, Fielding, Whyte, Martinez, Calder and Rodrigues.)

Aim: A digital rectal examination (DRE) during routine assessment for patients with abdominal symptoms provides an opportunity to obtain faeces from the glove for faecal immunochemical testing (FIT). Here, we compared sampling via DRE to the standard faecal sampling by patients., Method: Patients were recruited to a prospective observational cohort study between July 2019 and March 2020. Patients provided a sample for the FOB Gold Wide ® which was compared to a further sample taken at clinic via DRE. Clinicians reported whether they obtained a 'good' sample filling all the grooves, a 'poor' sample filling some of the grooves or no faecal sample. Cohen's kappa was used to compare percentage agreement around a negative threshold of <10 μg haemoglobin/g of faeces. Sensitivity for serious bowel disease (SBD) was calculated., Results: Of 596 patients who underwent attempted DRE sampling, there were 258 (43.3%) 'good' samples, 117 (19.6%) 'poor' samples and 221 (37.1%) with no sample to wipe in the grooves. Cohen's kappa dropped from 0.70 to 0.30 for the 'good' and 'poor' samples, respectively. Of those with DRE samples and definitive diagnostic outcomes, the sensitivity for SBD dropped significantly from 76.0% to 41.7% between 'good' and 'poor' samples, respectively ( p = 0.041)., Conclusions: A 'good' sample obtained by DRE provides comparable results to samples obtained by patients. This creates potential benefit in speed and ease of testing for patients. However, not all DRE sampling attempts are successful, and the clinician must be satisfied that enough faeces is obtained to wipe adequately into all grooves.

Aim: To determine the absolute risk reduction (ARR) of heart failure events in people treated with sodium-glucose co-transporter-2 (SGLT2) inhibitors., Materials and Methods: We searched PubMed, EMBASE, CINAHL and ISI Web of Science for observational studies published to 9 May 2022 that explored the association between SGLT2 inhibitors and any indication for heart failure (including new diagnosis or hospitalization for heart failure) in type 2 diabetes. Identified studies were independently screened by two reviewers and assessed for bias using the Newcastle-Ottawa scale. Eligible studies with comparable outcome data were pooled for meta-analysis using random-effects models, reporting hazard ratios (HRs) with 95% confidence intervals (CIs). The ARR per 100 person-years was determined overall, and in subgroups with and without baseline cardiovascular disease (CVD)., Results: From 43 eligible studies, with a total of 4 818 242 participants from 17 countries, 21 were included for meta-analysis. SGLT2 inhibitors were associated with a reduced risk of hospitalization for heart failure (HR 0.65, 95% CI 0.59-0.72) overall and both in those with CVD (HR 0.78, 95% CI 0.68-0.89) and without CVD (HR 0.53, 95% CI 0.39-0.71). Risk reduction for hospitalization for heart failure in people with a history of CVD (ARR 1.17, 95% CI 0.78-1.55) was significantly greater than for those without CVD (ARR 0.39, 95% CI 0.32-0.47). The number-needed-to-treat to prevent one event of hospitalization for heart failure was 86 (95% CI 65-128) person-years of treatment for the CVD group and 256 (95% CI 215-316) person-years for those without CVD., Conclusions: Real-world SGLT2 inhibitor use supports randomized trial data for the size effect of reduced hospitalization for heart failure in type 2 diabetes, although with a much lower ARR in people without CVD., (© 2022 John Wiley & Sons Ltd.)

Aims: There has been uncertainty whether SGLT2 inhibition predisposes to hyperkalaemia or is protective from it. We therefore performed a meta-analysis to assess effects of SGLT2 inhibition on serum-potassium and hyperkalaemia-events in T2DM., Methods: MEDLINE and PubMed databases were searched for 'hyperkalaemia' or 'potassium', with SGLT2 inhibitors in T2DM, to 31st December 2020. Randomised controlled trials, with potassium or hyperkalaemia as primary or secondary outcomes, were included. Cochran's Q test and I 2 statistic assessed statistical heterogeneity. Meta-analyses were performed using Cochrane-RevMan with two outcomes: i) Odds ratio (OR) of hyperkalaemia-events between SGLT2 inhibitor and placebo (fixed-effects), ii) Mean difference (MD) in change from baseline potassium between SGLT2 inhibitor and placebo (random-effects)., Results: Of 1724 identified publications, nine were included in the meta-analysis (n = 3 hyperkalaemia event; n = 5 serum-potassium; n = 1 reported both outcomes). Pooled OR for hyperkalaemia-events for SGLT2 inhibitor vs placebo was 0.72 [95% confidence interval (CI) 0.61 to 0.85, P < 0.001], I 2 of 9%. The pooled MD in serum-potassium concentration with SGLT2 inhibitor vs placebo was -0.04 mmol/L [95% CI -0.08 to 0.00 mmol/L; P = 0.04], I 2 of 89%., Conclusions: Use of SGLT2 inhibitors in T2DM reduced odds of inducing hyperkalaemia but had a minimal effect of lowering serum potassium., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘MBW holds investigator-led research grant with AstraZeneca and previous funding from Eli Lilly. Speaker and Consultancy fees from MSD, Boehringer and AstraZeneca.’, (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Glycaemic control associates with better outcomes for hospitalised patients. Whether GLP-1 receptor agonists (GLP-1 RA) are suitable and effective drugs for inpatients is unclear., Methods: A retrospective, single centre, observational study using data from the electronic health record. Patients admitted using GLP-1 RA as outpatients, from 2016 to 2019, were identified. Outcomes were compared to those admitted using twice-daily (BD) mixed insulin. Capillary glucose, medication use, creatinine, and demographic data were collected. As drugs may be discontinued/not administered in hospital, days when GLP-1 RA was administered were 'GLP-1 RA active' and, for insulin, 'insulin active'. The primary comparison was rate of hypoglycaemia (<4 mmol/L) and severe hypoglycaemia (<3 mmol/L). A logistic regression model examined variables for hypoglycaemia., Results: GLP-1 RA comprised n = 262 admissions and BD insulin n = 166. The 'insulin active' cohort (n = 957 patient days) had higher risk of hypoglycaemia than 'GLP-1 RA active' (n = 806 days); occurring on 14.7% of days; 95% confidence interval [CI] 12.6-17.1 versus 9.9% days; 95% CI 8.0-12.2; p = 0.002, and severe hypoglycaemia 4.0% of days (95% CI 2.8-5.4) versus 2.0% (95% CI 1.1%-3.2%; p = 0.005). Daily glucose (mean ± standard deviation) was 10.8 ± 5.2 mmol/L in insulin active versus 9.6 ± 4.7 mmol/L in GLP-1 RA active; p < 0.001. Insulin use, age, and acute admissions predicted hypoglycaemia. The odds ratio for hypoglycaemia was 2.15 times greater (95% CI, 1.14-4.08; p = 0.019) with insulin than with GLP-1 RA., Conclusions: GLP-1 RA provided better glycaemic control than BD mixed insulin and should be continued during hospitalisation unless there is a clear indication for cessation., (© 2022 John Wiley & Sons Ltd.)

Background : diabetes and age are major risk factors for the development of lower extremity peripheral artery disease (PAD). Cocoa flavanol (CF) consumption is associated with lower risk for PAD and improves brachial artery (BA) endothelial function. Objectives : to assess if femoral artery (FA) endothelial function and dermal microcirculation are impaired in individuals with type 2 diabetes mellitus (T2DM) and evaluate the acute effect of CF consumption on FA endothelial function. Methods : in a randomised, controlled, double-blind, cross-over study, 22 individuals ( n = 11 healthy, n = 11 T2DM) without cardiovascular disease were recruited. Participants received either 1350 mg CF or placebo capsules on 2 separate days in random order. Endothelial function was measured as flow-mediated dilation (FMD) using ultrasound of the common FA and the BA before and 2 hours after interventions. The cutaneous microvasculature was assessed using optical coherence tomography angiography. Results : baseline FA-FMD and BA-FMD were significantly lower in T2DM (FA: 3.2 ± 1.1% [SD], BA: 4.8 ± 0.8%) compared to healthy (FA: 5.5 ± 0.7%, BA: 6.0 ± 0.8%); each p < 0.001. Whereas in healthy individuals FA-FMD did not significantly differ from BA-FMD ( p = 0.144), FA-FMD was significantly lower than BA-FMD in T2DM ( p = 0.003) indicating pronounced and additional endothelial dysfunction of lower limb arteries (FA-FMD/BA-FMD: 94 ± 14% [healthy] vs. 68 ± 22% [T2DM], p = 0.007). The baseline FA blood flow rate (0.42 ± 0.23 vs. 0.73 ± 0.35 l min -1 , p = 0.037) and microvascular dilation in response to occlusion in hands and feet were significantly lower in T2DM subjects than in healthy ones. CF increased both FA- and BA-FMD at 2 hours, compared to placebo, in both healthy and T2DM subgroups (FA-FMD effect: 2.9 ± 1.4%, BA-FMD effect 3.0 ± 3.5%, each p intervention < 0.001). In parallel, baseline FA blood flow and microvascular diameter significantly increased in feet (3.5 ± 3.5 μm, p intervention < 0.001) but not hands. Systolic blood pressure and pulse wave velocity significantly decreased after CF in both subgroups (-7.2 ± 9.6 mmHg, p intervention = 0.004; -1.3 ± 1.3 m s -1 , p intervention = 0.002). Conclusions : individuals with T2DM exhibit decreased endothelial function that is more pronounced in the femoral than in the brachial artery. CFs increase endothelial function not only in the BA but also the FA both in healthy individuals and in those with T2DM who are at increased risk of developing lower extremity PAD and foot ulcers.

Background: Weight loss, hyperglycaemia and diabetes are known features of pancreatic cancer. We quantified the timing and the amount of changes in body mass index (BMI) and glycated haemoglobin (HbA1c), and their association with pancreatic cancer from five years before diagnosis., Methods: A matched case-control study was undertaken within 590 primary care practices in England, United Kingdom. 8,777 patients diagnosed with pancreatic cancer (cases) between 1st January 2007 and 31st August 2020 were matched to 34,979 controls by age, gender and diabetes. Longitudinal trends in BMI and HbA1c were visualised. Odds ratios adjusted for demographic and lifestyle factors (aOR) and 95% confidence intervals (CI) were calculated with conditional logistic regression. Subgroup analyses were undertaken according to the diabetes status., Results: Changes in BMI and HbA1c observed for cases on longitudinal plots started one and two years (respectively) before diagnosis. In the year before diagnosis, a 1 kg/m2 decrease in BMI between cases and controls was associated with aOR for pancreatic cancer of 1.05 (95% CI 1.05 to 1.06), and a 1 mmol/mol increase in HbA1c was associated with aOR of 1.06 (1.06 to 1.07). ORs remained statistically significant (p < 0.001) for 2 years before pancreatic cancer diagnosis for BMI and 3 years for HbA1c. Subgroup analysis revealed that the decrease in BMI was associated with a higher pancreatic cancer risk for people with diabetes than for people without (aORs 1.08, 1.06 to 1.09 versus 1.04, 1.03 to 1.05), but the increase in HbA1c was associated with a higher risk for people without diabetes than for people with diabetes (aORs 1.09, 1.07 to 1.11 versus 1.04, 1.03 to 1.04)., Conclusions: The statistically significant changes in weight and glycaemic control started three years before pancreatic cancer diagnosis but varied according to the diabetes status. The information from this study could be used to detect pancreatic cancer earlier than is currently achieved. However, regular BMI and HbA1c measurements are required to facilitate future research and implementation in clinical practice., Competing Interests: The authors have declared that no competing interests exist.

Aim: To determine whether achieving early glycaemic control, and any subsequent glycaemic variability, was associated with any change in the risk of major adverse cardiovascular events (MACE)., Materials and Methods: A retrospective cohort analysis from the Oxford-Royal College of General Practitioners Research and Surveillance Centre database-a large, English primary care network-was conducted. We followed newly diagnosed patients with type 2 diabetes, on or after 1 January 2005, aged 25 years or older at diagnosis, with HbA1c measurements at both diagnosis and after 1 year, plus five or more measurements of HbA1c thereafter. Three glycaemic bands were created: groups A (HbA1c < 58 mmol/mol [<7.5%]), B (HbA1c ≥ 58 to 75 mmol/mol [7.5%-9.0%]) and C (HbA1c ≥ 75 mmol/mol [≥9.0%]). Movement between bands was determined from diagnosis to 1 year. Additionally, for data after the first 12 months, a glycaemic variability score was calculated from the number of successive HbA1c readings differing by 0.5% or higher (≥5.5 mmol/mol). Risk of MACE from 1 year postdiagnosis was assessed using time-varying Cox proportional hazards models, which included the first-year transition and the glycaemic variability score., Results: From 26 180 patients, there were 2300 MACE. Compared with group A->A transition over 1 year, those with C->A transition had a reduced risk of MACE (HR 0.75; 95% CI 0.60-0.94; P = .014), whereas group C->C had HR 1.21 (0.81-1.81; P = .34). Compared with the lowest glycaemic variability score, the greatest variability increased the risk of MACE (HR 1.51; 1.11-2.06; P = .0096)., Conclusion: Early control of HbA1c improved cardiovascular outcomes in type 2 diabetes, although subsequent glycaemic variability had a negative effect on an individual's risk., (© 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

The electronic health record has dramatically improved the safety of medical care as well as the clarity and accessibility of the notes. An equally profound, but under-recognised consequence, is the effect it has had on 'patient ownership' and responsibility within the hospital. It is now very easy to access and read through patients notes, from a distance and at scale, to identify patients for attention. Automated alerts can be set for quantitative laboratory or physiological variables, for the same purpose, and artificial intelligence is being developed for alerts based on free text or radiographic interpretation. This article explores the risk of this approach to healthcare and the danger of a 'collusion of anonymity', whereby responsibility for care is sufficiently diffuse that no one has ownership of a patient's care., (© Royal College of Physicians 2022 All rights reserved.)

There is a bidirectional relationship between hepatitis C and type 2 diabetes. The risk for developing type 2 diabetes is increased in patients with chronic hepatitis C virus (HCV) infection-with the prevalence of diabetes ranging from 13% to 33%. This is likely underpinned by insulin resistance. Type 2 diabetes may also be a predisposing factor for HCV infection. The new non-interferon-based therapeutic regimens for hepatitis C have transformed care and can eradicate disease. In this report, we show how such a regimen eradicated viral load, improved hepatocellular blood markers and significantly improved dysglycaemia, such that all glucose-lowering medication could be stopped., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Chronic kidney disease (CKD) is a serious, progressive condition associated with significant patient morbidity. Hypertension control and use of renin-angiotensin system blockers are the cornerstones of treatment for CKD. However, even with these treatment strategies, many individuals will progress towards kidney failure. Recently, sodium-glucose cotransporter 2 (SGLT2) inhibitor clinical trials with primary renal endpoints have firmly established SGLT2 inhibition, in addition to standard of care, as an effective strategy to slow down the progression of CKD and reduce some of its associated complications. The emergence of this new clinical evidence supports the use of SGLT2 inhibitors in the management of CKD in people with and without diabetes. As licensing and guidelines for SGLT2 inhibitors are updated, there is a need to adapt CKD treatment pathways and for this class of drugs to be included as part of standard care for CKD management. In this article, we have used consensus opinion alongside the available evidence to provide support for the healthcare community involved in CKD management, regarding the role of SGLT2 inhibitors in clinical practice. By highlighting appropriate prescribing and practical considerations, we aim to encourage greater and safe use of SGLT2 inhibitors for people with CKD, both with and without diabetes., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Aims: In populations of black African ancestry (BA), a paradox exists whereby lower visceral adipose tissue is found despite their high risk for type 2 diabetes (T2D). This systematic review investigates ethnic differences in other ectopic fat depots (intrahepatic lipid: IHL; intramyocellular lipid: IMCL and intrapancreatic lipid; IPL) to help contextualise their potential contribution to T2D risk., Methods: A systematic literature search was performed in December 2020 to identify studies reporting at least one ectopic fat comparison between BA and one/more other ethnicity. For IHL, a meta-analysis was carried out with studies considered comparable based on the method of measurement., Results: Twenty-eight studies were included (IHL: n = 20; IMCL: n = 8; IPL: n = 4). Meta-analysis of 11 studies investigating IHL revealed that it was lower in BA populations vs pooled ethnic comparators (MD -1.35%, 95% CI -1.55 to -1.16, I 2  = 85%, P < 0.00001), white European ancestry (MD -0.94%, 95% CI -1.17 to -0.70, I 2  = 79%, P < 0.00001), Hispanic ancestry (MD -2.06%, 95% CI -2.49 to -1.63, I 2  = 81%, P < 0.00001) and South Asian ancestry comparators (MD -1.92%, 95% CI -3.26 to -0.57, I 2  = 78%, P = 0.005). However, heterogeneity was high in all analyses. Most studies found no significant differences in IMCL between BA and WE. Few studies investigated IPL, however, indicated that IPL is lower in BA compared to WE and HIS., Conclusion: The discordance between ectopic fat and greater risk for T2D in BA populations raises questions around its contribution to T2D pathophysiology in BA., (© 2021. The Author(s).)

Background: The Acute Medical Unit (AMU) provides care for unscheduled hospital admissions. Seven-day consultant presence and morning AMU discharges have been advocated to improve hospital bed management., Aims: To determine whether a later time of daily peak AMU occupancy correlates with measures of hospital stress; whether 7-day consultant presence, for COVID-19, abolished weekly periodicity of discharges., Design: Retrospective cohort analysis., Methods: : Anonymised AMU admission and discharge times were retrieved from the Profile Information Management System (PIMS), at a large, urban hospital from 14 April 2014 to 31 December 2018 and 20 March to 2 May 2020 (COVID-19 peak). Minute-by-minute admission and discharge times were combined to construct a running total of AMU bed occupancy. Fourier transforms were used to determine periodicity. We tested association between (i) average AMU occupancy and (ii) time of peak AMU occupancy, with measures of hospital stress (total medical bed occupancy and 'medical outliers' on non-medical wards)., Results: : Daily, weekly and seasonal patterns of AMU bed occupancy were evident. Timing of AMU peak occupancy was unrelated to each measure of hospital stress: total medical inpatients (Spearman's rho, rs = 0.04, P = 0.24); number of medical outliers (rs = -0.06, P = 0.05). During COVID-19, daily bed occupancy was similar, with continuation of greater Friday and Monday discharges than the weekend., Conclusions: : Timing of peak AMU occupancy did not alter with hospital stress. Efforts to increase morning AMU discharges are likely to have little effect on hospital performance. Seven-day consultant presence did not abolish weekly periodicity of discharges-other factors influence weekend discharges., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Chronic kidney disease (CKD) is a complex disease which affects approximately 13% of the world's population. Over time, CKD can cause renal dysfunction and progression to end-stage kidney disease and cardiovascular disease. Complications associated with CKD may contribute to the acceleration of disease progression and the risk of cardiovascular-related morbidities. Early CKD is asymptomatic, and symptoms only present at later stages when complications of the disease arise, such as a decline in kidney function and the presence of other comorbidities associated with the disease. In advanced stages of the disease, when kidney function is significantly impaired, patients can only be treated with dialysis or a transplant. With limited treatment options available, an increasing prevalence of both the elderly population and comorbidities associated with the disease, the prevalence of CKD is set to rise. This review discusses the current challenges and the unmet patient need in CKD., (© 2021. The Author(s).)

The article by Subbe et al raise important considerations as to what is deemed quality care in medicine. Throughput in acute medicine is highly prized. Prompt decision making, and action, is certainly required for several groups of unwell patients, but there is system-wide pressure to maintain this fast pace for all patients. It does not automatically follow that quicker medicine benefits all patients to some degree. 'Productivity' may come at the cost of too much medicine - characterised by overdiagnosis, overtreatment, and substantial resource utilisation.

Introduction: The COVID-19 vaccination programme is under way worldwide. Anecdotal evidence is increasing that some people with type 1 diabetes mellitus (T1DM) experience temporary instability of blood glucose (BG) levels post-vaccination which normally settles within 2-3 days. We report an analysis of BG profiles of 20 individuals before/after vaccination., Methods: We examined the BG profile of 20 consecutive adults (18 years of age or more) with T1DM using the FreeStyle Libre flash glucose monitor in the period immediately before and after COVID-19 vaccination. The primary outcome measure was percentage (%) BG readings in the designated target range 3.9-10 mmmol/L as reported on the LibreView portal for 7 days prior to the vaccination (week -1) and the 7 days after the vaccination (week +1)., Results: There was a significant decrease in the %BG on target following the COVID-vaccination for the 7 days following vaccination (mean 45.2% ± SE 4.2%) vs pre-COVID-19 vaccination (mean 52.6% ± SE 4.5%). This was mirrored by an increase in the proportion of readings in other BG categories 10.1%-13.9%/≥14%. There was no significant change in BG variability in the 7days post-COVID-19 vaccination. This change in BG proportion on target in the week following vaccination was most pronounced for people taking Metformin/Dapagliflozin+basal-bolus insulin (-23%) vs no oral hypoglycaemic agents (-4%), and median age <53 vs ≥53 years (greater reduction in %BG in target for older individuals (-18% vs -9%))., Conclusion: In T1DM, we have shown that COVID-19 vaccination can cause temporary perturbation of BG, with this effect more pronounced in patients talking oral hypoglycaemic medication plus insulin, and in older individuals. This may also have consequences for patients with T2DM who are currently not supported by flash glucose monitoring., (© 2021 John Wiley & Sons Ltd.)