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Aims To assess whether glycaemic control is associated with prognosis in people with cancer and pre-existing diabetes. Methods In this pre-registered systematic review (PROSPERO: CRD42020223956), PubMed and Web of Science were searched on 25th Nov 2021 for studies investigating associations between glycosylated haemoglobin (HbA 1c ) and prognosis in people with diabetes and cancer. Summary relative risks (RRs) and 95% Confidence Intervals (CIs) for associations between poorly controlled HbA 1c or per 1-unit HbA 1c increment and cancer outcomes were estimated using a random-effects meta-analysis. We also investigated the impact of potential small-study effects using the trim-and-fill method and potential sources of heterogeneity using subgroup analyses. Results Fifteen eligible observational studies, reporting data on 10,536 patients with cancer and pre-existing diabetes, were included. Random-effects meta-analyses indicated that HbA 1c  ≥ 7% (53 mmol/mol) was associated with increased risks of: all-cause mortality (14 studies; RR: 1.14 [95% CI: 1.03–1.27]; p-value : 0.012), cancer-specific mortality (5; 1.68 [1.13–2.49]; p-value : 0.011) and cancer recurrence (8; 1.68 [1.18–2.38; p-value : 0.004]), with moderate to high heterogeneity. Dose-response meta-analyses indicated that 1-unit increment of HbA 1c (%) was associated with increased risks of all-cause mortality (13 studies; 1.04 [1.01–1.08]; p-value : 0.016) and cancer-specific mortality (4; 1.11 [1.04–1.20]; p-value : 0.003). All RRs were attenuated in trim-and-fill analyses. Conclusions Our findings suggested that glycaemic control might be a modifiable risk factor for mortality and cancer recurrence in people with cancer and pre-existing diabetes. High-quality studies with a larger sample size are warranted to confirm these findings due to heterogeneity and potential small-study effects. In the interim, it makes clinical sense to recommend continued optimal glycaemic control. Highlights • Diabetes is a common comorbidity in newly-diagnosed cancer patients. • The impact of glycaemic control in people with both cancer and diabetes is unclear. • In this meta-analysis, cancer prognosis is worse in those with poor HbA 1c control. • More studies with larger sample sizes are warranted to confirm these findings. • Clinicians should continue to ensure HbA 1c control in cancer patients with diabetes.

ObjectivesWe hypothesised that there is substantial variation in acute myocardial infarction (AMI) treatment across English hospitals, particularly for people hospitalised for non-ST-elevation myocardial infarction (NSTEMI) and with reduced kidney function. This study aimed to describe this variation at the hospital and the individual level to understand treatment variation and potential disparities in AMI management among people with reduced kidney function.DesignCross-sectional study.SettingSecondary care in England.ParticipantsPeople hospitalised for AMI (ST-elevation myocardial infarction (STEMI) or NSTEMI) in English hospitals and captured in the Myocardial Ischaemia National Audit Project, 2014 to 2019. Kidney function was defined using estimated glomerular filtration rate (eGFR) derived from the serum creatinine recorded within 24 hours of AMI admission.Outcome measureThe primary outcome was recorded invasive cardiac intervention (at least one of angiography, percutaneous coronary intervention and coronary artery bypass graft) compared with conservative management.ResultsWe included 361 259 people with a first hospitalisation for AMI (STEMI or NSTEMI) at 209 hospitals for hospital-level analyses and 292 572 people with complete covariable data at 207 hospitals for individual-level analyses. We found substantial variation in the mean proportion of people with NSTEMI managed invasively across hospitals in England. At the individual level, using multivariable logistic regression to derive adjusted predicted probabilities to describe the association between kidney function and AMI management (invasive vs conservative management), we found that people had a lower adjusted predicted probability of being treated with invasive cardiac management with worsening eGFR range, particularly for NSTEMI cases (eGFR range 2: 76.6% (95% CI 76.3 to 76.8) vs eGFR range 5: 44.5% (95% CI 41.2 to 47.5)).ConclusionsThere is substantial AMI treatment variation across hospitals in England, particularly among people hospitalised for NSTEMI with reduced kidney function. Further research is needed to evaluate the comparative effectiveness of NSTEMI management strategies for complex patients.

Aortic distensibility (AD) is important for the prognosis of multiple cardiovascular diseases. We propose a novel resource-efficient deep learning (DL) model, inspired by the bi-directional ConvLSTM U-Net with densely connected convolutions, to perform end-to-end hierarchical learning of the aorta from cine cardiovascular MRI towards streamlining AD quantification. Unlike current DL aortic segmentation approaches, our pipeline: (i) performs simultaneous spatio-temporal learning of the video input, (ii) combines the feature maps from the encoder and decoder using non-linear functions, and (iii) takes into account the high class imbalance. By using multi-centre multi-vendor data from a highly heterogeneous patient cohort, we demonstrate that the proposed method outperforms the state-of-the-art method in terms of accuracy and at the same time it consumes ∼ 3.9 times less fuel and generates ∼ 2.8 less carbon emissions. Our model could provide a valuable tool for exploring genome-wide associations of the AD with the cognitive performance in large-scale biomedical databases. By making energy usage and carbon emissions explicit, the presented work aligns with efforts to keep DL’s energy requirements and carbon cost in check. The improved resource efficiency of our pipeline might open up the more systematic DL-powered evaluation of the MRI-derived aortic stiffness.

ObjectiveTo examine the association between practice percentage coding of chronic kidney disease (CKD) in primary care with risk of subsequent hospitalisations and death.DesignRetrospective cohort study using linked electronic healthcare records.Setting637 general practitioner (GP) practices in England.Participants167 208 patients with CKD stages 3–5 identified by 2 measures of estimated glomerular filtration rate <60 mL/min/1.73 m2, separated by at least 90 days, excluding those with coded initiation of renal replacement therapy.Main outcome measuresHospitalisations with cardiovascular (CV) events, heart failure (HF), acute kidney injury (AKI) and all-cause mortalityResultsParticipants were followed for (median) 3.8 years for hospital outcomes and 4.3 years for deaths. Rates of hospitalisations with CV events and HF were lower in practices with higher percentage CKD coding. Trends of a small reduction in AKI but no substantial change in rate of deaths were also observed as CKD coding increased. Compared with patients in the median performing practice (74% coded), patients in practices coding 55% of CKD cases had a higher rate of CV hospitalisations (HR 1.061 (95% CI 1.015 to 1.109)) and HF hospitalisations (HR 1.097 (95% CI 1.013 to 1.187)) and patients in practices coding 88% of CKD cases had a reduced rate of CV hospitalisations (HR 0.957 (95% CI 0.920 to 0.996)) and HF hospitalisations (HR 0.918 (95% CI 0.855 to 0.985)). We estimate that 9.0% of CV hospitalisations and 16.0% of HF hospitalisations could be prevented by improving practice CKD coding from 55% to 88%. Prescription of antihypertensives was the most dominant predictor of a reduction in hospitalisation rates for patients with CKD, followed by albuminuria testing and use of statins.ConclusionsHigher levels of CKD coding by GP practices were associated with lower rates of CV and HF events, which may be driven by increased use of antihypertensives and regular albuminuria testing, although residual confounding cannot be ruled out.

Background Acute myocardial infarction (AMI) causes significant mortality and morbidity in people with impaired kidney function. Previous observational research has demonstrated reduced use of invasive management strategies and inferior outcomes in this population. Studies from the USA have suggested that disparities in care have reduced over time. It is unclear whether these findings extend to Europe and the UK. Methods Linked data from four national healthcare datasets were used to investigate management and outcomes of AMI by estimated glomerular filtration rate (eGFR) category in England. Multivariable logistic and Cox regression models compared management strategies and outcomes by eGFR category among people with kidney impairment hospitalised for AMI between 2015–2017. Results In a cohort of 5 835 people, we found reduced odds of invasive management in people with eGFR < 60mls/min/1.73m 2 compared with people with eGFR ≥ 60 when hospitalised for non-ST segment elevation MI (NSTEMI). The association between eGFR and odds of invasive management for ST-elevation MI (STEMI) varied depending on the availability of percutaneous coronary intervention. A graded association between mortality and eGFR category was demonstrated both in-hospital and after discharge for all people. Conclusions In England, patients with reduced eGFR are less likely to receive invasive management compared to those with preserved eGFR. Disparities in care may however be decreasing over time, with the least difference seen in patients with STEMI managed via the primary percutaneous coronary intervention pathway. Reduced eGFR continues to be associated with worse outcomes after AMI.

Non-atherosclerotic abnormalities of vessel calibre, aneurysm and ectasia, are challenging to quantify and are often overlooked in qualitative reporting. Utilising a novel 3-dimensional (3D) quantitative coronary angiography (QCA) application, we have evaluated the characteristics of normal, diabetic and aneurysmal or ectatic coronary arteries. We selected 131 individuals under 50 years-of-age, who had undergone coronary angiography for suspected myocardial ischaemia between 1st January 2011 and 31st December 2015, at the Bristol Heart Institute, Bristol, UK. This included 42 patients with angiographically normal coronary arteries, 36 diabetic patients with unobstructed coronaries, and 53 patients with abnormal coronary dilatation (aneurysm and ectasia). A total of 1105 coronary segments were analysed using QAngio XA 3D (Research Edition, Medis medical imaging systems, Leiden, The Netherlands). The combined volume of the major coronary arteries was significantly different between each group (1240 ± 476 mm 3 diabetic group, 1646 ± 391 mm 3 normal group, and 2072 ± 687 mm 3 abnormal group). Moreover, the combined coronary artery volumes correlated with patient body surface area (r = 0.483, p  < 0.01). Inter-observer variability was assessed and intraclass correlation coefficient of the total coronary artery volume demonstrated a low variability of 3D QCA (r = 0.996, p  < 0.001). Dedicated 3D QCA facilitates reproducible coronary artery volume estimation and allows discrimination of normal and diseased vessels.

ObjectivesAcute myocardial infarction (AMI) case ascertainment improves for the UK general population using linked health data sets. Because care pathways for people with chronic kidney disease (CKD) change based on disease severity, AMI case ascertainment for these people may differ compared with the general population. We aimed to determine the association between CKD severity and AMI case ascertainment in two secondary care data sets, and the agreement in estimated glomerular filtration rate (eGFR) between the same data sets.MethodsWe used a cohort study design. Primary care records for people with CKD or risk factors for CKD, identified using the National CKD Audit (2015–2017), were linked to the Myocardial Ischaemia National Audit Project (MINAP, 2007–2017) and Hospital Episode Statistics (HES, 2007–2017) secondary care registries. People with an AMI recorded in either MINAP, HES or both were included in the study cohort. CKD status was defined using eGFR, derived from the most recent serum creatinine value recorded in primary care. Moderate–severe CKD was defined as eGFR <60 mL/min/1.73 m2, and mild CKD or at risk of CKD was defined as eGFR ≥60 mL/min/1.73 m2 or eGFR missing. CKD stages were grouped as (1) At risk of CKD and Stages 1–2 (eGFR missing or ≥60 mL/min/1.73 m2), (2) Stage 3a (eGFR 45–59 mL/min/1.73 m2), (3) Stage 3b (eGFR 30–44 mL/min/1.73 m2) and (4) Stages 4–5 (eGFR <30 mL/min/1.73 m2).ResultsWe identified 6748 AMIs: 23% were recorded in both MINAP and HES, 66% in HES only and 11% in MINAP only. Compared with people at risk of CKD or with mild CKD, AMIs in people with moderate–severe CKD were more likely to be recorded in both MINAP and HES (42% vs 11%, respectively), or MINAP only (22% vs 5%), and less likely to be recorded in HES only (36% vs 84%). People with AMIs recorded in HES only or MINAP only had increased odds of death during hospitalisation compared with those recorded in both (adjusted OR 1.61, 95% CI 1.32 to 1.96 and OR 1.60, 95% CI 1.26 to 2.04, respectively). Agreement between eGFR at AMI admission (MINAP) and in primary care was poor (kappa (K) 0.42, SE 0.012).ConclusionsAMI case ascertainment is incomplete in both MINAP and HES, and is associated with CKD severity.

BackgroundAortic stenosis is a life-limiting condition for which transcatheter aortic valve implantation (TAVI) is an established therapy. Coronary artery disease (CAD) is frequently found in this patient group and optimal management in these patients remains uncertain.ObjectivesWe sought to examine the association of coexistent CAD on mortality and hospital readmission in patients undergoing TAVI.MethodsIn this observational cohort study, we examined patients who underwent TAVI and segregated them by the presence of obstructive epicardial CAD. The primary outcome was 3-year mortality with secondary outcomes being readmission for (1) all-causes, (2) a MACE (Major Adverse Cardiovascular Event) composite endpoint and (3) acute coronary syndrome. Subsidiary outcomes included patient angina and breathlessness scores.Results898 patients underwent TAVI, of which 488 (54.3%) had unobstructed coronary arteries and 410 (45.7%) had obstructive CAD. Overall, n=298 (33.2%) patients experienced the primary mortality endpoint with no significant difference when stratified according to CAD (n=160 (32.9%) vs n=136 (33.2%), HR 0.98, CI 0.78 to 1.24). After multivariate analysis, the presence of CAD had no effect on the primary outcome (HR 0.98, CI 0.68 to 1.40). There was no significant difference in readmission for any cause (n=181, 37.1% (CAD) vs n=169, 41.2% (no CAD), p=0.23), including no significant difference on readmission for MACE (n=48, 9.8% (CAD) vs n=45, 11.0% (no CAD), p=0.11). CAD at the time of TAVI also did not alter breathlessness or angina scores before/after TAVI (p>0.05).ConclusionCoexistent CAD had no significant association with mortality, any-cause readmission or symptoms for patients undergoing TAVI in our cohort.

Approved therapies for the treatment of patients with pulmonary arterial hypertension (PAH) mediate pulmonary vascular vasodilatation by targeting distinct biological pathways. International guidelines recommend that patients with an inadequate response to dual therapy with a phosphodiesterase type‐5 inhibitor (PDE5i) and endothelin receptor antagonist (ERA), are recommended to either intensify oral therapy by adding a selective prostacyclin receptor (IP) agonist (selexipag), or switching from PDE5i to a soluble guanylate‐cyclase stimulator (sGCS; riociguat). The clinical equipoise between these therapeutic choices provides the opportunity for evaluation of individualized therapeutic effects. Traditionally, invasive/hospital‐based investigations are required to comprehensively assess disease severity and demonstrate treatment benefits. Regulatory‐approved, minimally invasive monitors enable equivalent measurements to be obtained while patients are at home. In this 2 × 2 randomized crossover trial, patients with PAH established on guideline‐recommended dual therapy and implanted with CardioMEMS™ (a wireless pulmonary artery sensor) and ConfirmRx™ (an insertable cardiac rhythm monitor), will receive ERA + sGCS, or PDEi + ERA + IP agonist. The study will evaluate clinical efficacy via established clinical investigations and remote monitoring technologies, with remote data relayed through regulatory‐approved online clinical portals. The primary aim will be the change in right ventricular systolic volume measured by magnetic resonance imaging (MRI) from baseline to maximal tolerated dose with each therapy. Using data from MRI and other outcomes, including hemodynamics, physical activity, physiological measurements, quality of life, and side effect reporting, we will determine whether remote technology facilitates early evaluation of clinical efficacy, and investigate intra‐patient efficacy of the two treatment approaches.