Journal articles
Strain W, Griffiths J (In Press). A systematic review and meta-analysis of the impact of GLP-1 receptor agonists and SGLT-2 inhibitors on cardiovascular outcomes in biologically healthy older adults. The British Journal of Diabetes
Strain W, Down S, Brown P, Puttanna A, Sinclair A (In Press). Diabetes and Frailty: an Expert Consensus Statement on the Management of Older Adults with Type 2 Diabetes. Diabetes Therapy
Strain WD, Paldanius PM (In Press). Dipeptidyl Peptidase-4 Inhibitor Development and Post-authorisation Programme for Vildagliptin. European Endocrinology
Strain W (In Press). Effects of semaglutide on stroke subtypes in type 2 diabetes: post hoc analysis of the randomised SUSTAIN 6 & PIONEER 6.
Stroke,
53Abstract:
Effects of semaglutide on stroke subtypes in type 2 diabetes: post hoc analysis of the randomised SUSTAIN 6 & PIONEER 6
Background: Glucagon-like peptide-1 receptor agonists, including semaglutide, may reduce stroke risk in people with type 2 diabetes (T2D). This post hoc analysis examined the subcutaneous and oral semaglutide effects, versus placebo, on stroke and its subtypes in people with T2D at high cardiovascular (CV) risk.
Methods: SUSTAIN 6 and PIONEER 6 were randomised CV outcome trials of subcutaneous and oral semaglutide in people with T2D at high CV risk, respectively. Time to first stroke and stroke subtypes were analysed using a Cox proportional hazards model stratified by trial with pooled treatment as a factor. The impact of prior stroke, prior myocardial infarction or stroke, age, sex, systolic blood pressure, estimated glomerular filtration rate, and prior atrial fibrillation on treatment effects was assessed using interaction p-values. Risk of major adverse CV event (MACE) was analysed according to prior stroke.
Results: 106/6480 participants had a stroke (1.0 event/100 patient-years of observation [PYO]). Semaglutide reduced incidence of any stroke versus placebo (0.8 vs 1.1 events/100 PYO; HR 0.68, 95%CI 0.46–1.00;p=0.048), driven by significant reductions in risk of small-vessel occlusion (0.3 vs 0.7 events/100 PYO; HR 0.51, 95%CI 0.29–0.89;p=0.017). HRs for risk of any stroke with semaglutide versus placebo were 0.60 (95%CI 0.37–0.99; 0.5 vs 0.9 events/100 PYO) and 0.89 (95%CI 0.47–1.69; 2.7 vs 3.0 events/100 PYO) in those without and with prior stroke, respectively. Except for prior atrial fibrillation (pinteraction=0.025), no significant interactions were observed between treatment effects on risk of any stroke and subgroups investigated, or between treatment effects on risk of MACE and prior stroke (pinteraction>0.05 for all).
Conclusions: Semaglutide reduced incidence of any first stroke during the trials versus placebo in people with T2D at high CV risk, primarily driven by small-vessel occlusion prevention. Semaglutide treatment, versus placebo, lowered the risk of stroke irrespective of prior stroke at baseline.
Clinical Trial Registration Information: SUSTAIN 6: NCT01720446 (https://clinicaltrials.gov/ct2/show/NCT01720446); PIONEER 6: NCT02692716 (https://clinicaltrials.gov/ct2/show/NCT02692716).
Abstract.
Rinaldi G (In Press). Epidemiological Model Based Periodic Intervention Policies
for COVID-19 Mitigation in the United Kingdom. Nature Scientific Reports
Zirk-Sadowski J, Masoli J, Strain WD, Delgado J, Henley W, Hamilton W, Melzer D, Ble A (In Press). Proton-Pump Inhibitors and Fragility Fractures in Vulnerable Older Patients. The American Journal of Gastroenterology (Elsevier)
evans M, Morgan A, Davies S, beba H, Strain W (In Press). The role of Sodium-glucose co-transporter-2 (SGLT2) inhibitors in frail older adults with or without type 2 diabetes mellitus (T2DM). Age and Ageing
Strain WD, Morgan A, Evans M (In Press). The value of insulin degludec in frail older adults with type 2 diabetes. Diabetes Therapy
Casanova F, Gooding K, Shore A, Adingupu D, Mawson D, Ball C, Anning C, Aizawa K, Gates P, Strain W, et al (In Press). Weight change and sulphonylurea therapy are related to three-year change in microvascular function in people with type 2 diabetes. Diabetologia
Allan L, O'Connell A, Raghuraman S, Bingham A, Laverick A, Chandler K, Connors J, Jones B, Um J, Morgan-Trimmer S, et al (2023). A rehabilitation intervention to improve recovery after an episode of delirium in adults over 65 years (RecoverED): study protocol for a multi-centre, single-arm feasibility study.
Pilot Feasibility Stud,
9(1).
Abstract:
A rehabilitation intervention to improve recovery after an episode of delirium in adults over 65 years (RecoverED): study protocol for a multi-centre, single-arm feasibility study.
BACKGROUND: Delirium affects over 20% of all hospitalised older adults. Delirium is associated with a number of adverse outcomes following hospital admission including cognitive decline, anxiety and depression, increased mortality and care needs. Previous research has addressed prevention of delirium in hospitals and care homes, and there are guidelines on short-term treatment of delirium during admission. However, no studies have addressed the problem of longer-term recovery after delirium and it is currently unknown whether interventions to improve recovery after delirium are effective and cost-effective. The primary objective of this feasibility study is to test a new, theory-informed rehabilitation intervention (RecoverED) in older adults delivered following a hospital admission complicated by delirium to determine whether (a) the intervention is acceptable to individuals with delirium and (b) a definitive trial and parallel economic evaluation of the intervention are feasible. METHODS: the study is a multi-centre, single-arm feasibility study of a rehabilitation intervention with an embedded process evaluation. Sixty participants with delirium (aged > 65 years old) and carer pairs will be recruited from six NHS acute hospitals across the UK. All pairs will be offered the intervention, with follow-up assessments conducted at 3 months and 6 months post-discharge home. The intervention will be delivered in participants' own homes by therapists and rehabilitation support workers for up to 10 intervention sessions over 12 weeks. The intervention will be tailored to individual needs, and the chosen intervention plan and goals will be discussed and agreed with participants and carers. Quantitative data on reach, retention, fidelity and dose will be collected and summarised using descriptive statistics. The feasibility outcomes that will be used to determine whether the study meets the criteria for progression to a definitive randomised controlled trial (RCT) include recruitment, delivery of the intervention, retention, data collection and acceptability of outcome measures. Acceptability of the intervention will be assessed using in-depth, semi-structured qualitative interviews with participants and healthcare professionals. DISCUSSION: Findings will inform the design of a pragmatic multi-centre RCT of the effectiveness and cost-effectiveness of the RecoverED intervention for helping the longer-term recovery of people with delirium compared to usual care. TRIAL REGISTRATION: the feasibility study was registered: ISRCTN15676570.
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Author URL.
Strain WD, Davies S, Chowdhury S (2023). Long COVID and myalgic encephalomyelitis: opportunities for understanding and research. British Journal of Healthcare Management, 29(6), 1-3.
Alwan NA, Clutterbuck D, Pantelic M, Hayer J, Fisher L, Hishmeh L, Heightman M, Allsopp G, Wootton D, Khan A, et al (2023). Long Covid active case finding study protocol: a co-produced community-based pilot within the STIMULATE-ICP study (Symptoms, Trajectory, Inequalities and Management: Understanding Long-COVID to Address and Transform Existing Integrated Care Pathways).
PLoS ONE,
18(7 July).
Abstract:
Long Covid active case finding study protocol: a co-produced community-based pilot within the STIMULATE-ICP study (Symptoms, Trajectory, Inequalities and Management: Understanding Long-COVID to Address and Transform Existing Integrated Care Pathways)
Background and aim Long Covid is a significant public health concern with potentially negative implications for health inequalities. We know that those who are already socially disadvantaged in society are more exposed to COVID-19, experience the worst health outcomes and are more likely to suffer economically. We also know that these groups are more likely to experience stigma and have negative healthcare experiences even before the pandemic. However, little is known about disadvantaged groups' experiences of Long Covid, and preliminary evidence suggests they may be under-represented in those who access formal care. We will conduct a pilot study in a defined geographical area in London, United Kingdom to test the feasibility of a community-based approach of identifying Long Covid cases that have not been clinically diagnosed and have not been referred to Long Covid specialist services. We will explore the barriers to accessing recognition, care, and support, as well as experiences of stigma and perceived discrimination. Methods This protocol and study materials were co-produced with a Community Advisory Board (CAB) made up primarily of people living with Long Covid. Working with voluntary organisations, a study leaflet will be distributed in the local community to highlight Long Covid symptoms and invite those experiencing them to participate in the study if they are not formally diagnosed. Potential participants will be assessed according to the study's inclusion criteria and offered the opportunity to participate if they fit them. Awareness of Long Covid and associated symptoms, experiences of trying to access care, as well as stigma and discrimination will be explored through qualitative interviews with participants. Upon completion of the interviews, participants will be offered a referral to the local social prescribing team to receive support that is personalised to them potentially including, but not restricted to, liaising with their primary care provider and the regional Long Covid clinic.
Abstract.
Van der Feltz-Cornelis CM, Moriarty AS, Strain WD (2023). Neurological Dysfunction in Long COVID Should Not be Labelled as Functional Neurological Disorder.
Viruses,
15(3), 783-783.
Abstract:
Neurological Dysfunction in Long COVID Should Not be Labelled as Functional Neurological Disorder
There have been suggestions that Long COVID might be purely functional (meaning psychological) in origin. Labelling patients with neurological dysfunction in Long COVID as having functional neurological disorder (FND) in the absence of proper testing may be symptomatic of that line of thought. This practice is problematic for Long COVID patients, as motor and balance symptoms have been reported to occur in Long COVID frequently. FND is characterized by the presentation of symptoms that seem neurological but lack compatibility of the symptom with a neurological substrate. Although diagnostic classification according to the ICD-11 and DSM-5-TR is dependent predominantly on the exclusion of any other medical condition that could account for the symptoms, current neurological practice of FND classification allows for such comorbidity. As a consequence, Long COVID patients with motor and balance symptoms mislabeled as FND have no longer access to Long COVID care, whereas treatment for FND is seldom provided and is ineffective. Research into underlying mechanisms and diagnostic methods should explore how to determine whether motor and balance symptoms currently diagnosed as FND should be considered one part of Long COVID symptoms, in other words, one component of symptomatology, and in which cases they correctly represent FND. Research into rehabilitation models, treatment and integrated care are needed, which should take into account biological underpinnings as well as possible psychological mechanisms and the patient perspective.
Abstract.
Yu D, Brown J, David Strain W, Simmons D (2023). Real-world evidence that among atrial fibrillation patients warfarin is associated with reduced nonelective admissions compared with those on DOACs.
Clin CardiolAbstract:
Real-world evidence that among atrial fibrillation patients warfarin is associated with reduced nonelective admissions compared with those on DOACs.
BACKGROUND: Randomized trials show inconsistent estimates on risks of direct-acting oral anticoagulants (DOACs) versus warfarin in bleeding and mortality for atrial fibrillation (AF) patients. Trials are confounded by additional DOAC adherence support, while warfarin has a low time in therapeutic range. Few real-world studies compared emergency hospitalization risk between DOAC and warfarin users in AF. This study aimed to determine emergency hospitalization risk for AF patients on DOACs or warfarin in real-world settings. METHODS: a tapered-matched real-world cohort extracted data from 412 English general practices' primary care records linked with emergency department (ED) and hospitalization data from the ECLIPSE database. AF patients with new DOAC or warfarin prescriptions were included. The primary outcome was all-cause ED attendance; the secondary outcomes were ED re-attendance, nonelective hospitalization, and rehospitalization within 12 months. Weighted Cox regression estimated relative risk difference. RESULTS: 39 201 DOAC patients were matched with 13 145 warfarin patients. DOAC patients had a 25% higher likelihood of attending ED (odds ratio 1.25; 95% confidence interval [CI] 1.01-1.55). DOAC use also associated with higher ED re-attendance, nonelective hospitalization, and rehospitalization within 12 months: 1.41 (95% CI 1.00-1.98), 1.26 (1.00-1.57), and 1.54 (1.01-2.34), respectively, with p-values
Abstract.
Author URL.
Forshaw D, Wall EC, Prescott G, Dehbi H-M, Green A, Attree E, Hismeh L, Strain WD, Crooks MG, Watkins C, et al (2023). STIMULATE-ICP: a pragmatic, multi-centre, cluster randomised trial of an integrated care pathway with a nested, Phase III, open label, adaptive platform randomised drug trial in individuals with Long COVID: a structured protocol.
PLoS One,
18(2).
Abstract:
STIMULATE-ICP: a pragmatic, multi-centre, cluster randomised trial of an integrated care pathway with a nested, Phase III, open label, adaptive platform randomised drug trial in individuals with Long COVID: a structured protocol.
INTRODUCTION: Long COVID (LC), the persistent symptoms ≥12 weeks following acute COVID-19, presents major threats to individual and public health across countries, affecting over 1.5 million people in the UK alone. Evidence-based interventions are urgently required and an integrated care pathway approach in pragmatic trials, which include investigations, treatments and rehabilitation for LC, could provide scalable and generalisable solutions at pace. METHODS AND ANALYSIS: This is a pragmatic, multi-centre, cluster-randomised clinical trial of two components of an integrated care pathway (Coverscan™, a multi-organ MRI, and Living with COVID Recovery™, a digitally enabled rehabilitation platform) with a nested, Phase III, open label, platform randomised drug trial in individuals with LC. Cluster randomisation is at level of primary care networks so that integrated care pathway interventions are delivered as "standard of care" in that area. The drug trial randomisation is at individual level and initial arms are rivaroxaban, colchicine, famotidine/loratadine, compared with no drugs, with potential to add in further drug arms. The trial is being carried out in 6-10 LC clinics in the UK and is evaluating the effectiveness of a pathway of care for adults with LC in reducing fatigue and other physical, psychological and functional outcomes at 3 months. The trial also includes an economic evaluation which will be described separately. ETHICS AND DISSEMINATION: the protocol was reviewed by South Central-Berkshire Research Ethics Committee (reference: 21/SC/0416). All participating sites obtained local approvals prior to recruitment. Coverscan™ has UK certification (UKCA 752965). All participants will provide written consent to take part in the trial. The first participant was recruited in July 2022 and interim/final results will be disseminated in 2023, in a plan co-developed with public and patient representatives. The results will be presented at national and international conferences, published in peer reviewed medical journals, and shared via media (mainstream and social) and patient support organisations. TRIAL REGISTRATION NUMBER: ISRCTN10665760.
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Author URL.
Williams J, Gilchrist M, Strain WD, Fraser D, Shore A (2022). 24-h Glycaemic profiles in peritoneal dialysis patients and non-dialysis controls with advanced kidney disease.
Perit Dial Int,
42(5), 497-504.
Abstract:
24-h Glycaemic profiles in peritoneal dialysis patients and non-dialysis controls with advanced kidney disease.
BACKGROUND: for patients on peritoneal dialysis (PD), the deleterious effects of high concentrations of dialysate glucose on the peritoneal membrane are well-documented. Systemic effects of peritoneally absorbed glucose are more poorly defined. Using continuous glucose monitoring (CGM), we aimed to describe 24-h glycaemic profiles of PD patients without diabetes and compare with non-dialysis controls with stage 5 chronic kidney disease (CKD-5). METHODS: in this cross-sectional, case-control study, 15 patients on PD (9 automated PD (APD) and 6 continuous ambulatory PD (CAPD)) and 16 CKD-5 controls underwent 72 h of CGM and metabolic profiling. CGM was used to derive average glucose concentrations and within-participant standard deviation (SD) of glucose. Data were analysed for the whole 72-h monitoring period and as daytime (09.00 to 21.00) and night-time (21.00 to 09.00). RESULTS: Average glucose concentrations and within-participant SD of glucose for the whole monitoring period were not different between the three groups (p ≥ 0.5). Daytime average glucose concentrations were also similar across the three groups (p = 0.729). APD was associated with a significantly higher nocturnal glucose than CAPD (5.25 mmol/L ± 0.65 vs. 4.28 ± 0.5, p = 0.026). A significant drop in nocturnal glucose compared with daytime average seen in both CAPD patients and controls was absent in APD patients. CONCLUSIONS: Systematically different glycaemic patterns were observed in non-diabetic APD and CAPD patients, including an absence of physiological nocturnal glucose dipping in patients on APD. Comprehensive CGM data sets highlight subtleties not appreciated by traditional metabolic biomarkers; this has implications when choosing the most appropriate outcome measures in future research addressing the metabolic impact of PD.
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Author URL.
Evans M, Lewis RD, Morgan AR, Whyte MB, Hanif W, Bain SC, Davies S, Dashora U, Yousef Z, Patel DC, et al (2022). A Narrative Review of Chronic Kidney Disease in Clinical Practice: Current Challenges and Future Perspectives.
Adv Ther,
39(1), 33-43.
Abstract:
A Narrative Review of Chronic Kidney Disease in Clinical Practice: Current Challenges and Future Perspectives.
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.
Abstract.
Author URL.
Williams J, Gilchrist M, Strain WD, Fraser D, Shore A (2022). An exploratory study of the relationship between systemic microcirculatory function and small solute transport in incident peritoneal dialysis patients.
Perit Dial Int,
42(5), 513-521.
Abstract:
An exploratory study of the relationship between systemic microcirculatory function and small solute transport in incident peritoneal dialysis patients.
BACKGROUND: the peritoneal capillary endothelium is widely considered to be the most influential structure in dictating the rate of small solute transport (SST) during peritoneal dialysis (PD). PD patients are at significant risk of systemic microcirculatory dysfunction. The relationship between peritoneal and systemic microcirculations in patients new to PD has not been well studied. We hypothesised that for patients on PD for less than 6 months, dysfunction in the systemic microcirculation would be reflected in the rate of SST. METHODS: We recruited 29 patients to a cross-sectional, observational study. Rate of SST was measured using a standard peritoneal equilibration test. Laser Doppler Flowmetry was used to measure response to physical and pharmacological challenge (post-occlusive hyperaemic response and iontophoretic application of vasodilators) in the cutaneous microcirculation. Sidestream Darkfield imaging was used to assess sublingual microvascular density, flow and endothelial barrier properties. RESULTS: We found no moderate or strong correlations between any of the measures of systemic microcirculatory function and rate of SST or albumin clearance. There was however a significant correlation between dialysate interleukin-6 concentrations and both SST (rs = 0.758 p ≤ 0.0001) and albumin clearance (rs = 0.53, p = 0.01). CONCLUSIONS: in this study, systemic microvascular dysfunction did not significantly influence the rate of SST even early in patients PD careers. In conclusion, this study demonstrates that intraperitoneal factors particularly inflammation have a far greater impact on rate of SST than systemic factors.
Abstract.
Author URL.
Evans M, Morgan AR, Bain SC, Davies S, Dashora U, Sinha S, Seidu S, Patel DC, Beba H, Strain WD, et al (2022). Defining the Role of SGLT2 Inhibitors in Primary Care: Time to Think Differently.
Diabetes Ther,
13(5), 889-911.
Abstract:
Defining the Role of SGLT2 Inhibitors in Primary Care: Time to Think Differently.
Disease burden in people with diabetes is mainly driven by long-term complications such as cardiovascular disease, heart failure and chronic kidney disease. This is a consequence of the interconnection between the cardiovascular, renal and metabolic systems, through a continuous chain of events referred to as 'the cardiorenal metabolic continuum'. Increasing evidence suggests that sodium-glucose cotransporter 2 inhibitors (SGLT2is) have beneficial effects across all stages of the cardiorenal metabolic continuum, reducing morbidity and mortality in a wide range of individuals, from those with diabetes and multiple risk factors to those with established heart failure and chronic kidney disease, regardless of the presence of diabetes. Despite this robust evidence base, the complexity of label indications and misconceptions concerning potential side effects have resulted in a lack of clear understanding in primary care regarding the implementation of SGLT2is in clinical practice. With this in mind, we provide an overview of the clinical and economic benefits of SGLT2is across the cardiorenal metabolic continuum together with practical considerations in order to help address some of these concerns and clearly define the role of SGLT2is in primary care as a holistic outcomes-driven treatment with the potential to reduce disease burden across the cardiorenal metabolic spectrum.
Abstract.
Author URL.
Heath R, Johnsen H, Strain WD, Evans M (2022). Emerging Horizons in Heart Failure with Preserved Ejection Fraction: the Role of SGLT2 Inhibitors.
Diabetes Ther,
13(2), 241-250.
Abstract:
Emerging Horizons in Heart Failure with Preserved Ejection Fraction: the Role of SGLT2 Inhibitors.
Heart failure with preserved ejection fraction (HFpEF) is a condition with increasing disease burden. Prevalence of HFpEF is increasing, reflecting an increasingly elderly and comorbid population, as well as reinforcing the need for more treatments for this disease. The pathophysiology of HFpEF is complex. Some inflammatory processes seen in HFpEF are shared with diabetes mellitus (DM) and there is an association seen between the two conditions. It is therefore no wonder that treatments for diabetes may have some effect on heart failure outcomes. Current treatment strategies in HFpEF are limited, with treatments focusing on symptom control rather than morbidity or mortality benefit. However, there are now promising results from the EMPEROR-Preserved study that show significantly reduced cardiovascular death or hospitalisation for heart failure (HHF) in patients taking empagliflozin, compared to those taking placebo. These results indicate a promising future for sodium-glucose co-transporter 2 (SGLT2) inhibitors in HFpEF. The ongoing DELIVER trial (investigating the use of dapagliflozin in HFpEF) is awaited but could provide further evidence of support for SGLT2 inhibitors in HFpEF. With hospital admissions for HFpEF increasing in the UK, the economic impact of treatments that reduce HHF is vast. The European Society of Cardiology (ESC) recently added SGLT2 inhibitors to their guidelines for treatment of heart failure with reduced ejection fraction (HFrEF) following DAPA-HF and EMPEROR-Reduced trials and we suggest that similar changes be made to guidelines to support the use of SGLT2 inhibitors in the management of HFpEF in upcoming months.
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Evans M, Morgan AR, Bain SC, Davies S, Hicks D, Brown P, Yousef Z, Dashora U, Viljoen A, Beba H, et al (2022). Meeting the Challenge of Virtual Diabetes Care: a Consensus Viewpoint on the Positioning and Value of Oral Semaglutide in Routine Clinical Practice.
Diabetes Ther,
13(2), 225-240.
Abstract:
Meeting the Challenge of Virtual Diabetes Care: a Consensus Viewpoint on the Positioning and Value of Oral Semaglutide in Routine Clinical Practice.
While glucagon-like peptide-1 receptor agonists (GLP-1 RAs), such as semaglutide, are among the most effective drugs for treating people with type 2 diabetes (T2D), they are clinically under-utilised. Until recently, the only route for semaglutide administration was via subcutaneous injection. However, an oral formulation of semaglutide was recently licensed, with the potential to address therapy inertia and increase patient adherence to treatment, which is essential in controlling blood glucose and reducing complications. The availability of oral semaglutide provides a new option for both clinicians and patients who are reluctant to use an injectable agent. This has been of particular importance in addressing the challenge of virtual diabetes care during the COVID-19 pandemic, circumventing the logistical problems that are often associated with subcutaneous medication administration. However, there remains limited awareness of the clinical and economic value of oral semaglutide in routine clinical practice. In this article, we present our consensus opinion on the role of oral semaglutide in routine clinical practice and discuss its value in reducing the burden of delivering diabetes care in the post-COVID-19 pandemic period of chronic disease management.
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Author URL.
Evans M, Morgan AR, Whyte MB, Hanif W, Bain SC, Kalra PA, Davies S, Dashora U, Yousef Z, Patel DC, et al (2022). New Therapeutic Horizons in Chronic Kidney Disease: the Role of SGLT2 Inhibitors in Clinical Practice.
Drugs,
82(2), 97-108.
Abstract:
New Therapeutic Horizons in Chronic Kidney Disease: the Role of SGLT2 Inhibitors in Clinical Practice.
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.
Abstract.
Author URL.
Khan F, Gonçalves I, Shore AC, Natali A, Palombo C, Colhoun HM, Östling G, Casanova F, Kennbäck C, Aizawa K, et al (2022). Plaque characteristics and biomarkers predicting regression and progression of carotid atherosclerosis.
Cell Rep Med,
3(7).
Abstract:
Plaque characteristics and biomarkers predicting regression and progression of carotid atherosclerosis.
The factors that influence the atherosclerotic disease process in high-risk individuals remain poorly understood. Here, we used a combination of vascular imaging, risk factor assessment, and biomarkers to identify factors associated with 3-year change in carotid disease severity in a cohort of high-risk subjects treated with preventive therapy (n = 865). The results show that changes in intima-media thickness (IMT) are most pronounced in the carotid bulb. Progression of bulb IMT demonstrates independent associations with baseline bulb IMT, the plaque gray scale median (GSM), and the plasma level of platelet-derived growth factor (PDGF) (standardized β-coefficients and 95% confidence interval [CI] -0.14 [-0.06 to -0.02] p = 0.001, 0.15 [0.02-0.07] p = 0.001, and 0.20 [0.03-0.07] p
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Alghamdi F, Owen R, Ashton REM, Obotiba AD, Meertens RM, Hyde E, Faghy MA, Knapp KM, Rogers P, Strain WD, et al (2022). Post-acute COVID syndrome (long COVID): What should radiographers know and the potential impact for imaging services. Radiography, 28, S93-S99.
Strain D (2022). Removing special covid leave will only undervalue staff and threaten patient safety. The BMJ
van der Feltz-Cornelis CM, Sweetman J, Allsopp G, Attree E, Crooks MG, Cuthbertson DJ, Forshaw D, Gabbay M, Green A, Heightman M, et al (2022). STIMULATE-ICP-Delphi (Symptoms, Trajectory, Inequalities and Management: Understanding Long-COVID to Address and Transform Existing Integrated Care Pathways Delphi): Study protocol.
PLoS ONE,
17(11).
Abstract:
STIMULATE-ICP-Delphi (Symptoms, Trajectory, Inequalities and Management: Understanding Long-COVID to Address and Transform Existing Integrated Care Pathways Delphi): Study protocol
Introduction As mortality rates from COVID-19 disease fall, the high prevalence of long-term sequelae (Long COVID) is becoming increasingly widespread, challenging healthcare systems globally. Traditional pathways of care for Long Term Conditions (LTCs) have tended to be managed by disease-specific specialties, an approach that has been ineffective in delivering care for patients with multi-morbidity. The multi-system nature of Long COVID and its impact on physical and psychological health demands a more effective model of holistic, integrated care. The evolution of integrated care systems (ICSs) in the UK presents an important opportunity to explore areas of mutual benefit to LTC, multi-morbidity and Long COVID care. There may be benefits in comparing and contrasting ICPs for Long COVID with ICPs for other LTCs. Methods and analysis This study aims to evaluate health services requirements for ICPs for Long COVID and their applicability to other LTCs including multi-morbidity and the overlap with medically not yet explained symptoms (MNYES). The study will follow a Delphi design and involve an expert panel of stakeholders including people with lived experience, as well as clinicians with expertise in Long COVID and other LTCs. Study processes will include expert panel and moderator panel meetings, surveys, and interviews. The Delphi process is part of the overall STIMULATE-ICP programme, aimed at improving integrated care for people with Long COVID. Ethics and dissemination Ethical approval for this Delphi study has been obtained (Research Governance Board of the University of York) as have approvals for the other STIMULATE-ICP studies. Study outcomes are likely to inform policy for ICPs across LTCs. Results will be disseminated through scientific publication, conference presentation and communications with patients and stakeholders involved in care of other LTCs and Long COVID.
Abstract.
Strain WD, Sherwood O, Banerjee A, Van der Togt V, Hishmeh L, Rossman J (2022). The Impact of COVID Vaccination on Symptoms of Long COVID: an International Survey of People with Lived Experience of Long COVID.
Vaccines,
10(5).
Abstract:
The Impact of COVID Vaccination on Symptoms of Long COVID: an International Survey of People with Lived Experience of Long COVID
Long COVID is a multi-system syndrome following SARS-CoV-2 infection with persistent symptoms of at least 4 weeks, and frequently for several months. It has been suggested that there may be an autoimmune component. There has been an understandable caution amongst some people experiencing long COVID that, by boosting their immune response, a COVID vaccine may exacerbate their symptoms. We aimed to survey people living with long COVID, evaluating the impact of their first COVID vaccination on their symptoms. Methods: Patients with long COVID were invited to complete a web-based questionnaire through postings on social media and direct mailing from support groups. Basic demographics, range and severity of long COVID symptoms, before and after their vaccine, were surveyed. Results: 900 people participated in the questionnaire, of whom 45 had pre-existing myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) but no evidence of COVID infection, and a further 43 did not complete the survey in full. The demographics and symptomology of the remaining 812 people were similar to those recorded by the UK Office of National Statistics. Following vaccination, 57.9% of participants reported improvements in symptoms, 17.9% reported deterioration and the remainder no change. There was considerable individual variation in responses. Larger improvements in symptom severity scores were seen in those receiving the mRNA vaccines compared to adenoviral vector vaccines. Conclusions: Our survey suggests COVID-19 vaccination may improve long COVID patients, on average. The observational nature of the survey limits drawing direct causal inference, but requires validation with a randomised controlled trial.
Abstract.
Shiri T, Evans M, Talarico CA, Morgan AR, Mussad M, Buck PO, McEwan P, Strain WD (2022). The Population-Wide Risk-Benefit Profile of Extending the Primary COVID-19 Vaccine Course Compared with an mRNA Booster Dose Program.
Vaccines,
10(2), 140-140.
Abstract:
The Population-Wide Risk-Benefit Profile of Extending the Primary COVID-19 Vaccine Course Compared with an mRNA Booster Dose Program
The vaccination program is reducing the burden of COVID-19. However, recently, COVID-19 infections have been increasing across Europe, providing evidence that vaccine efficacy is waning. Consequently, booster doses are required to restore immunity levels. However, the relative risk–benefit ratio of boosters, compared to pursuing a primary course in the unvaccinated population, remains uncertain. In this study, a susceptible-exposed-infectious-recovered (SEIR) transmission model of SARS-CoV-2 was used to investigate the impact of COVID-19 vaccine waning on disease burden, the benefit of a booster vaccine program compared to targeting the unvaccinated population, and the population-wide risk–benefit profile of vaccination. Our data demonstrates that the rate of vaccine efficacy waning has a significant impact on COVID-19 hospitalisations with the greatest effect in populations with lower vaccination coverage. There was greater benefit associated with a booster vaccination strategy compared to targeting the unvaccinated population, once >50% of the population had received their primary vaccination course. The population benefits of vaccination (reduced hospitalisations, long-COVID and deaths) outweighed the risks of myocarditis/pericarditis by an order of magnitude. Vaccination is important in ending the COVID-19 pandemic sooner, and the reduction in hospitalisations, death and long-COVID associated with vaccination significantly outweigh any risks. Despite these obvious benefits some people are vaccine reluctant, and as such remain unvaccinated. However, when most of a population have been vaccinated, a focus on a booster vaccine strategy for this group is likely to offer greater value, than targeting the proportion of the population who choose to remain unvaccinated.
Abstract.
He J, Bellenger NG, Ludman AJ, Shore AC, Strain WD (2022). Treatment of myocardial ischaemia-reperfusion injury in patients with ST-segment elevation myocardial infarction: promise, disappointment, and hope.
Rev Cardiovasc Med,
23(1).
Abstract:
Treatment of myocardial ischaemia-reperfusion injury in patients with ST-segment elevation myocardial infarction: promise, disappointment, and hope.
Acute myocardial infarction (AMI) is a major cause of morbidity and mortality worldwide. Timely reperfusion with primary percutaneous coronary intervention (PPCI) remains the gold standard in patients presenting with ST-segment elevation myocardial infarction (STEMI), limiting infarct size, preserving left ventricular ejection fraction (LVEF), and improving clinical outcomes. Despite this, a significant proportion of STEMI patients develop post-infarct heart failure. We review the current understanding and up-to-date evidence base for therapeutic intervention of ischaemia-reperfusion injury (IRI), a combination of myocardial ischaemia secondary to acute coronary occlusion and reperfusion injury leading to further myocardial injury and cell death. Multiple treatment modalities have been shown to be cardioprotective and reduce IRI in experimental animal models. Recent phase II/III randomised controlled trials (RCT) have assessed multiple cardioprotective strategies ranging from ischaemic conditioning, therapeutic hypothermia and hyperoxaemia to pharmacological therapies. While several therapies have been shown to reduce infarct size in animal models or proof-of-concept studies, many larger scale trial results have proven inconsistent and disappointing. Hard clinical outcomes remain elusive. We discuss potential reasons for the difficulties in translation to clinical practice.
Abstract.
Author URL.
Strain WD, Mansi J, Boikos C, Boivin M, Fisher WA (2021). Achieving Influenza Vaccine Uptake Target in Canada via a Pharmacy-Led Telephone Discussion during the 2019-2020 Season.
Vaccines (Basel),
9(4).
Abstract:
Achieving Influenza Vaccine Uptake Target in Canada via a Pharmacy-Led Telephone Discussion during the 2019-2020 Season.
Older adults (≥65 years) are at elevated risk of influenza-related morbidity and mortality. Many developed countries do not achieve the World Health Organization influenza immunization target of 75% in people ≥65 years. We aimed to determine whether a brief pharmacy phone call could increase vaccine uptake of standard and enhanced influenza. Twenty-eight community pharmacists across Canada performed a telephone consultation with 643 older adults whose primary care records indicated that they had not received their influenza vaccination from their usual practitioner. of these 643 adults, 169 (26.3%) had been vaccinated in another setting. of the remaining 474, 313 (66%) agreed to receive the vaccine. of those who refused vaccination, 69 provided a rationale for not wanting it, including that the flu shot "causes the flu" (n = 25), "doesn't work" (n = 25), "is too painful" (n = 10), and other (n = 10). Overall, of the 643 individuals who had not received their vaccination from their usual health care provider in the first wave of vaccinations, 75.4% (n = 485) ultimately received their vaccination in the 2019-2020 season. This highlights the important role of the community pharmacist in achieving the World Health Organization (WHO) targets for vaccination.
Abstract.
Author URL.
Geriatric Medicine Research Collaborative, Covid Collaborative, Welch C (2021). Age and frailty are independently associated with increased COVID-19 mortality and increased care needs in survivors: results of an international multi-centre study.
Age Ageing,
50(3), 617-630.
Abstract:
Age and frailty are independently associated with increased COVID-19 mortality and increased care needs in survivors: results of an international multi-centre study.
INTRODUCTION: Increased mortality has been demonstrated in older adults with coronavirus disease 2019 (COVID-19), but the effect of frailty has been unclear. METHODS: This multi-centre cohort study involved patients aged 18 years and older hospitalised with COVID-19, using routinely collected data. We used Cox regression analysis to assess the impact of age, frailty and delirium on the risk of inpatient mortality, adjusting for sex, illness severity, inflammation and co-morbidities. We used ordinal logistic regression analysis to assess the impact of age, Clinical Frailty Scale (CFS) and delirium on risk of increased care requirements on discharge, adjusting for the same variables. RESULTS: Data from 5,711 patients from 55 hospitals in 12 countries were included (median age 74, interquartile range [IQR] 54-83; 55.2% male). The risk of death increased independently with increasing age (>80 versus 18-49: hazard ratio [HR] 3.57, confidence interval [CI] 2.54-5.02), frailty (CFS 8 versus 1-3: HR 3.03, CI 2.29-4.00) inflammation, renal disease, cardiovascular disease and cancer, but not delirium. Age, frailty (CFS 7 versus 1-3: odds ratio 7.00, CI 5.27-9.32), delirium, dementia and mental health diagnoses were all associated with increased risk of higher care needs on discharge. The likelihood of adverse outcomes increased across all grades of CFS from 4 to 9. CONCLUSION: Age and frailty are independently associated with adverse outcomes in COVID-19. Risk of increased care needs was also increased in survivors of COVID-19 with frailty or older age.
Abstract.
Author URL.
Aizawa K, Gates PE, Mawson DM, Elyas S, Casanova F, Gooding KM, Adingupu DD, Strain WD, Shore AC (2021). Carotid–femoral pulse wave velocity acquisition methods and their associations with cardiovascular risk factors and subclinical biomarkers of vascular health.
Journal of Hypertension,
40(4), 658-665.
Abstract:
Carotid–femoral pulse wave velocity acquisition methods and their associations with cardiovascular risk factors and subclinical biomarkers of vascular health
. Background:
. Different methods to measure carotid–femoral pulse wave velocity (CFPWV) may affect the measurements obtained and influence the association between CFPWV, cardiovascular risk factors and biomarkers of subclinical vascular health. The estimation of distance between the carotid and femoral artery measurement sites (the arterial path length) is particularly problematic.
.
.
. Method:
. We determined if CFPWV and equation-based estimates of CFPWV were influenced by arterial path length and if this affected the association of CFPWV with cardiovascular risk factors and subclinical vascular biomarkers. The CFPWV derived from the measurement of surface distance (CFPWV-D), arterial path length formula (CFPWV-F), and estimated CFPWV (ePWV) were obtained from 489 older adults (67.2 ± 8.8 years). Macrovascular [carotid artery: lumen diameter (LD), inter-adventitial diameter (IAD), intima–media thickness (IMT) and total plaque area (TPA)] and microvascular [reactive hyperaemia index and urinary albumin-creatinine ratio (UACR)] biomarkers were also measured.
.
.
. Results:
. CFPWV-D was significantly greater than CFPWV-F [9.6 (8.0–11.2) vs. 8.9 (7.6–10.5) m/s, P < 0.001], because of estimated path length being longer in CFPWV-D than CFPWV-F (495.4 ± 44.8 vs. 465.3 ± 20.6 mm, P < 0.001). ePWV was significantly greater than both CFPWV-F and CFPWV-D [11.0 (10.0–12.2) m/s, P < 0.001]. The three CFPWV methods were similarly associated with LD, IAD, IMT, TPA and UACR but not with cardiovascular risk factors.
.
.
. Conclusion:
. Different methods to measure CFPWV affect the derived measurement values and the association with cardiovascular risk factors but not the association with subclinical biomarkers of vascular health. These hitherto unreported observations are important considerations in experimental design, data interpretation and of particular importance, comparison between studies where CFPWV is measured.
.
Abstract.
Elyas S, Adingupu D, Aizawa K, Casanova F, Gooding K, Fulford J, Mawson D, Gates PE, Shore AC, Strain D, et al (2021). Cerebral small vessel disease, systemic vascular characteristics and potential therapeutic targets. Aging, 13(18), 22030-22039.
Strain WD, Paldánius PM (2021). Correction to: Diabetes, cardiovascular disease and the microcirculation (Cardiovascular Diabetology, (2018), 17, 1, (57), 10.1186/s12933-018-0703-2).
Cardiovascular Diabetology,
20(1).
Abstract:
Correction to: Diabetes, cardiovascular disease and the microcirculation (Cardiovascular Diabetology, (2018), 17, 1, (57), 10.1186/s12933-018-0703-2)
An amendment to this paper has been published and can be accessed via the original article.
Abstract.
Strain WD, Jankowski J, Davies AP, English P, Friedman E, McKeown H, Sethi S, Rao M (2021). Development and presentation of an objective risk stratification tool for healthcare workers when dealing with the COVID-19 pandemic in the UK: risk modelling based on hospitalisation and mortality statistics compared with epidemiological data.
BMJ Open,
11(9), e042225-e042225.
Abstract:
Development and presentation of an objective risk stratification tool for healthcare workers when dealing with the COVID-19 pandemic in the UK: risk modelling based on hospitalisation and mortality statistics compared with epidemiological data
ObjectivesHealthcare workers have greater exposure to SARS-CoV-2 and an estimated 2.5-fold increased risk of contracting COVID-19 than the general population. We wished to explore the predictive role of basic demographics to establish a simple tool that could help risk stratify healthcare workers.SettingWe undertook a review of the published literature (including multiple search strategies in MEDLINE with PubMed interface) and critically assessed early reports on preprint servers. We explored the relative risk of mortality from readily available demographics to identify the population at the highest risk.ResultsThe published studies specifically assessing the risk of healthcare workers had limited demographics available; therefore, we explored the general population in the literature. Clinician demographics: Mortality increased with increasing age from 50 years onwards. Male sex at birth, and people of black and minority ethnicity groups had higher susceptibility to both hospitalisation and mortality. Comorbid disease. Vascular disease, renal disease, diabetes and chronic pulmonary disease further increased risk. Risk stratification tool: a risk stratification tool was compiled using a white female aged <50 years with no comorbidities as a reference. A point allocated to risk factors was associated with an approximate doubling in risk. This tool provides numerical support for healthcare workers when determining which team members should be allocated to patient facing clinical duties compared with remote supportive roles.ConclusionsWe generated a tool that provides a framework for objective risk stratification of doctors and healthcare professionals during the COVID-19 pandemic, without requiring disclosure of information that an individual may not wish to share with their direct line manager during the risk assessment process. This tool has been made freely available through the British Medical Association website and is widely used in the National Health Service and other external organisations.
Abstract.
Al-Shahi Salman R, Dennis MS, Sandercock PAG, Sudlow CLM, Wardlaw JM, Whiteley WN, Murray GD, Stephen J, Rodriguez A, Lewis S, et al (2021). Effects of Antiplatelet Therapy After Stroke Caused by Intracerebral Hemorrhage. JAMA Neurology, 78(10), 1179-1179.
Strain WD, Elyas S, Wedge N, Mounce L, Henley W, James M, Shore AC (2021). Evaluation of microalbuminuria as a prognostic indicator after a TIA or minor stroke in an outpatient setting: the prognostic role of microalbuminuria in TIA evolution (ProMOTE) study.
BMJ Open,
11(9), e043253-e043253.
Abstract:
Evaluation of microalbuminuria as a prognostic indicator after a TIA or minor stroke in an outpatient setting: the prognostic role of microalbuminuria in TIA evolution (ProMOTE) study
ObjectiveTransient ischaemic attacks (TIA) and minor strokes are important risk factors for further vascular events. We explored the role of albumin creatinine ratio (ACR) in improving risk prediction after a first event.SettingRapid access stroke clinics in the UK.Participants2202 patients attending with TIA or minor stroke diagnosed by the attending stroke physician, able to provide a urine sample to evaluate ACR using a near-patient testing device.Primary and secondary outcomesPrimary outcome was major adverse cardiac events (MACE: recurrent stroke, myocardial infarction or cardiovascular death) at 90 days. The key secondary outcome was to determine whether urinary ACR could contribute to a risk prediction tool for use in a clinic setting.Results151 MACE occurred in 144 participants within 90 days. Participants with MACE had higher ACR than those without. A composite score awarding a point each for age >80 years, previous stroke/TIA and presence of microalbuminuria identified those at low risk and high risk. 90% of patients were at low risk (scoring 0 or 1). Their 90-day risk of MACE was 5.7%. of the remaining ‘high-risk’ population (scoring 2 or 3) 12.4% experienced MACE over 90 days (p<0.001 compared with the low-risk population). The need for acute admission in the first 7 days was twofold elevated in the high-risk group compared with the low-risk group (3.23% vs 1.43%; p=0.05). These findings were validated in an independent historic sample.ConclusionA risk score comprising age, previous stroke/TIA and microalbuminuria predicts future MACE while identifying those at low risk of a recurrent event. This tool shows promise in the risk stratification of patients to avoid the admission of low-risk patients.
Abstract.
Maskery MP, Holscher C, Jones SP, Price CI, Strain WD, Watkins CL, Werring DJ, Emsley HCA (2021). Glucagon-like peptide-1 receptor agonists as neuroprotective agents for ischemic stroke: a systematic scoping review.
Journal of Cerebral Blood Flow and Metabolism,
41(1), 14-30.
Abstract:
Glucagon-like peptide-1 receptor agonists as neuroprotective agents for ischemic stroke: a systematic scoping review
Stroke mortality and morbidity is expected to rise. Despite considerable recent advances within acute ischemic stroke treatment, scope remains for development of widely applicable neuroprotective agents. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), originally licensed for the management of Type 2 Diabetes Mellitus, have demonstrated pre-clinical neuroprotective efficacy in a range of neurodegenerative conditions. This systematic scoping review reports the pre-clinical basis of GLP-1RAs as neuroprotective agents in acute ischemic stroke and their translation into clinical trials. We included 35 pre-clinical studies, 11 retrospective database studies, 7 cardiovascular outcome trials and 4 prospective clinical studies. Pre-clinical neuroprotection was demonstrated in normoglycemic models when administration was delayed by up to 24 h following stroke induction. Outcomes included reduced infarct volume, apoptosis, oxidative stress and inflammation alongside increased neurogenesis, angiogenesis and cerebral blood flow. Improved neurological function and a trend towards increased survival were also reported. Cardiovascular outcomes trials reported a significant reduction in stroke incidence with semaglutide and dulaglutide. Retrospective database studies show a trend towards neuroprotection. Prospective interventional clinical trials are on-going, but initial indicators of safety and tolerability are favourable. Ultimately, we propose that repurposing GLP-1RAs is potentially advantageous but appropriately designed trials are needed to determine clinical efficacy and cost-effectiveness.
Abstract.
Meertens R, Knapp KM, Strain WD, Casanova F, Ball S, Fulford J, Thorn C (2021). In vivo Measurement of Intraosseous Vascular Haemodynamic Markers in Human Bone Tissue Utilising Near Infrared Spectroscopy.
Frontiers in Physiology,
12Abstract:
In vivo Measurement of Intraosseous Vascular Haemodynamic Markers in Human Bone Tissue Utilising Near Infrared Spectroscopy
Objective:Poor vascular health is associated with reduced bone strength and increased risk of fragility fracture. However, direct measurement of intraosseous vascular health is difficult due to the density and mineral content of bone. We investigated the feasibility of using a commercially available continuous wave near infrared spectroscopy (NIRS) system for the investigation of vascular haemodynamics in human bonein vivo.Approach:An arterial occlusion (AO) protocol was developed for obtaining haemodynamic measurements of the proximal tibia and lateral calf, including assessment of the protocol’s intra operator reproducibility. For 36 participants, intraosseous haemodynamics derived by NIRS were compared to alternative tests of bone health based on dual x-ray absorptiometry (DXA) testing and MRI.Main Results:Near infrared spectroscopy markers of haemodynamics of the proximal tibia demonstrated acceptable reproducibility, comparable with reproducibility assessments of alternative modalities measuring intraosseous haemodynamics, and the use of NIRS for measuring muscle. Novel associations have been demonstrated between haemodynamic markers of bone measured with NIRS and body composition and bone mineral density (BMD) measurements obtained with both DXA and MRI.Significance:Near infrared spectroscopy provides inexpensive, non-invasive, safe, and real time data on changes in oxygenated and deoxygenated haemoglobin concentration in bone at the proximal tibia. This study has demonstrated the potential for NIRS to contribute to research investigating the pathophysiological role of vascular dysfunction within bone tissue, but also the limitations and need for further development of NIRS technology.
Abstract.
Aizawa K, Casanova F, Gates PE, Mawson DM, Gooding KM, Strain WD, Östling G, Nilsson J, Khan F, Colhoun HM, et al (2021). Reservoir-Excess Pressure Parameters Independently Predict Cardiovascular Events in Individuals with Type 2 Diabetes.
Hypertension,
78(1), 40-50.
Abstract:
Reservoir-Excess Pressure Parameters Independently Predict Cardiovascular Events in Individuals with Type 2 Diabetes
. The parameters derived from reservoir-excess pressure analysis have prognostic utility in several populations. However, evidence in type 2 diabetes (T2DM) remains scarce. We determined if these parameters were associated with T2DM and whether they would predict cardiovascular events in individuals with T2DM. We studied 306 people with T2DM with cardiovascular disease (CVD; DMCVD, 70.4±7.8 years), 348 people with T2DM but without CVD (diabetes mellitus, 67.7±8.4 years), and 178 people without T2DM or CVD (control group [CTRL], 67.2±8.9 years). Reservoir-excess pressure analysis–derived parameters, including reservoir pressure integral, peak reservoir pressure, excess pressure integral, systolic rate constant, and diastolic rate constant, were obtained by radial artery tonometry. Reservoir pressure integral was lower in DMCVD and diabetes mellitus than CTRL. Peak reservoir pressure was lower, and excess pressure integral was greater in DMCVD than diabetes mellitus and CTRL. Systolic rate constant was lower in a stepwise manner among groups (DMCVD< diabetes mellitus <CTRL). Diastolic rate constant was greater in DMCVD than CTRL. In the subgroup of individuals with T2DM (n=642), 14 deaths (6 cardiovascular and 9 noncardiovascular causes), and 108 cardiovascular events occurred during a 3-year follow-up period. Logistic regression analysis revealed that reservoir pressure integral (odds ratio, 0.59 [95% CI, 0.45–0.79]) and diastolic rate constant (odds ratio, 1.60 [95% CI, 1.25–2.06]) were independent predictors of cardiovascular events during follow-up after adjusting for conventional risk factors (both
. P
. <0.001). Further adjustments for potential confounders had no influence on associations. These findings demonstrate that altered reservoir-excess pressure analysis–derived parameters are associated with T2DM. Furthermore, baseline values of reservoir pressure integral and diastolic rate constant independently predict cardiovascular events in individuals with T2DM, indicating the potential clinical utility of these parameters for risk stratification in T2DM.
.
Abstract.
Shiri T, Evans M, Talarico CA, Morgan AR, Mussad M, Buck PO, McEwan P, Strain WD (2021). Vaccinating Adolescents and Children Significantly Reduces COVID-19 Morbidity and Mortality across all Ages: a Population-Based Modeling Study Using the UK as an Example.
Vaccines,
9(10), 1180-1180.
Abstract:
Vaccinating Adolescents and Children Significantly Reduces COVID-19 Morbidity and Mortality across all Ages: a Population-Based Modeling Study Using the UK as an Example
Debate persists around the risk–benefit balance of vaccinating adolescents and children against COVID-19. Central to this debate is quantifying the contribution of adolescents and children to the transmission of SARS-CoV-2, and the potential impact of vaccinating these age groups. In this study, we present a novel SEIR mathematical disease transmission model that quantifies the impact of different vaccination strategies on population-level SARS-CoV-2 infections and clinical outcomes. The model employs both age- and time-dependent social mixing patterns to capture the impact of changes in restrictions. The model was used to assess the impact of vaccinating adolescents and children on the natural history of the COVID-19 pandemic across all age groups, using the UK as an example. The base case model demonstrates significant increases in COVID-19 disease burden in the UK following a relaxation of restrictions, if vaccines are limited to those ≥18 years and vulnerable adolescents (≥12 years). Including adolescents and children in the vaccination program could reduce overall COVID-related mortality by 57%, and reduce cases of long COVID by 75%. This study demonstrates that vaccinating adolescents and children has the potential to play a vital role in reducing SARS-CoV-2 infections, and subsequent COVID-19 morbidity and mortality, across all ages. Our results have major global public health implications and provide valuable information to inform a potential pandemic exit strategy.
Abstract.
Casanova F, Wood AR, Yaghootkar H, Beaumont RN, Jones SE, Gooding KM, Aizawa K, Strain WD, Hattersley AT, Khan F, et al (2020). A Mendelian Randomization Study Provides Evidence That Adiposity and Dyslipidemia Lead to Lower Urinary Albumin-to-Creatinine Ratio, a Marker of Microvascular Function.
Diabetes,
69(5), 1072-1082.
Abstract:
A Mendelian Randomization Study Provides Evidence That Adiposity and Dyslipidemia Lead to Lower Urinary Albumin-to-Creatinine Ratio, a Marker of Microvascular Function.
Urinary albumin-to-creatinine ratio (ACR) is a marker of diabetic nephropathy and microvascular damage. Metabolic-related traits are observationally associated with ACR, but their causal role is uncertain. Here, we confirmed ACR as a marker of microvascular damage and tested whether metabolic-related traits have causal relationships with ACR. The association between ACR and microvascular function (responses to acetylcholine [ACH] and sodium nitroprusside) was tested in the SUMMIT study. Two-sample Mendelian randomization (MR) was used to infer the causal effects of 11 metabolic risk factors, including glycemic, lipid, and adiposity traits, on ACR. MR was performed in up to 440,000 UK Biobank and 54,451 CKDGen participants. ACR was robustly associated with microvascular function measures in SUMMIT. Using MR, we inferred that higher triglyceride (TG) and LDL cholesterol (LDL-C) levels caused elevated ACR. A 1 SD higher TG and LDL-C level caused a 0.062 (95% CI 0.040, 0.083) and a 0.026 (95% CI 0.008, 0.044) SD higher ACR, respectively. There was evidence that higher body fat and visceral body fat distribution caused elevated ACR, while a metabolically "favorable adiposity" phenotype lowered ACR. ACR is a valid marker for microvascular function. MR suggested that seven traits have causal effects on ACR, highlighting the role of adiposity-related traits in causing lower microvascular function.
Abstract.
Author URL.
Banerjee A, Benedetto V, Gichuru P, Burnell J, Antoniou S, Schilling RJ, Strain WD, Ryan R, Watkins C, Marshall T, et al (2020). Adherence and persistence to direct oral anticoagulants in atrial fibrillation: a population-based study.
Heart,
106(2), 119-126.
Abstract:
Adherence and persistence to direct oral anticoagulants in atrial fibrillation: a population-based study.
BACKGROUND: Despite simpler regimens than vitamin K antagonists (VKAs) for stroke prevention in atrial fibrillation (AF), adherence (taking drugs as prescribed) and persistence (continuation of drugs) to direct oral anticoagulants are suboptimal, yet understudied in electronic health records (EHRs). OBJECTIVE: We investigated (1) time trends at individual and system levels, and (2) the risk factors for and associations between adherence and persistence. METHODS: in UK primary care EHR (The Health Information Network 2011-2016), we investigated adherence and persistence at 1 year for oral anticoagulants (OACs) in adults with incident AF. Baseline characteristics were analysed by OAC and adherence/persistence status. Risk factors for non-adherence and non-persistence were assessed using Cox and logistic regression. Patterns of adherence and persistence were analysed. RESULTS: Among 36 652 individuals with incident AF, cardiovascular comorbidities (median CHA2DS2VASc[Congestive heart failure, Hypertension, Age≥75 years, Diabetes mellitus, Stroke, Vascular disease, Age 65-74 years, Sex category] 3) and polypharmacy (median number of drugs 6) were common. Adherence was 55.2% (95% CI 54.6 to 55.7), 51.2% (95% CI 50.6 to 51.8), 66.5% (95% CI 63.7 to 69.2), 63.1% (95% CI 61.8 to 64.4) and 64.7% (95% CI 63.2 to 66.1) for all OACs, VKA, dabigatran, rivaroxaban and apixaban. One-year persistence was 65.9% (95% CI 65.4 to 66.5), 63.4% (95% CI 62.8 to 64.0), 61.4% (95% CI 58.3 to 64.2), 72.3% (95% CI 70.9 to 73.7) and 78.7% (95% CI 77.1 to 80.1) for all OACs, VKA, dabigatran, rivaroxaban and apixaban. Risk of non-adherence and non-persistence increased over time at individual and system levels. Increasing comorbidity was associated with reduced risk of non-adherence and non-persistence across all OACs. Overall rates of 'primary non-adherence' (stopping after first prescription), 'non-adherent non-persistence' and 'persistent adherence' were 3.5%, 26.5% and 40.2%, differing across OACs. CONCLUSIONS: Adherence and persistence to OACs are low at 1 year with heterogeneity across drugs and over time at individual and system levels. Better understanding of contributory factors will inform interventions to improve adherence and persistence across OACs in individuals and populations.
Abstract.
Author URL.
Bain SC, Bakhai A, Evans M, Green A, Menown I, Strain WD (2020). An update to: Pharmacological treatment for type 2 diabetes integrating findings from cardiovascular outcome trials: an expert consensus in the UK. <i>Diabet Med</i> 2019; 36: 1063-1071.
DIABETIC MEDICINE,
37(8), 1405-1407.
Author URL.
Masoli JAH, Delgado J, Pilling L, Strain D, Melzer D (2020). Blood pressure in frail older adults: associations with cardiovascular outcomes and all-cause mortality.
Age Ageing,
49(5), 807-813.
Abstract:
Blood pressure in frail older adults: associations with cardiovascular outcomes and all-cause mortality.
BACKGROUND: Blood pressure (BP) management in frail older people is challenging. An randomised controlled trial of largely non-frail older people found cardiovascular and mortality benefit with systolic (S) BP target 150 mmHg. Associations with mortality varied between non-frail
Abstract.
Author URL.
Strain WD, Jankowski J, Davies A, English PMB, Friedman E, McKeown H, Sethi S, Rao M (2020). Development and Presentation of an Objective Risk Stratification Tool for healthcare workers when dealing with the COVID-19 pandemic in the UK: Risk modelling based on hospitalisation and mortality statistics compared to epidemiological data.
Abstract:
Development and Presentation of an Objective Risk Stratification Tool for healthcare workers when dealing with the COVID-19 pandemic in the UK: Risk modelling based on hospitalisation and mortality statistics compared to epidemiological data
AbstractObjectivesHealthcare workers have a greater exposure to individuals with confirmed SARS-novel coronavirus 2, and an estimated 5-fold higher probability of contracting coronavirus disease (COVID)-19, than the general population. Many organisations have called for risk assessments to be put in place to minimise this risk. We wished to explore the predictive role of basic demographics in order to establish a simple tool that could help risk stratify healthcare workers.SettingWe undertook a review of the published literature (including multiple search strategies in MEDLINE with PubMed interface) and critically assessed early reports on medRxiv, a pre-print server (https://www.medrxiv.org: date of last search: December 21, 2020). We explored the relative risk of mortality from readily available demographics in order to identify the population at highest risk.ResultsThe only published studies specifically assessing the risk of healthcare workers had limited demographics available, therefore we explored the general population in the literature.Clinician DemographicsMortality increased with increasing age from 50 years onwards. Male sex at birth, people of black and minority ethnicity groups had higher susceptibility to both hospitalisation and mortality. Co-morbid Disease. Vascular disease, renal disease, diabetes and chronic pulmonary disease further increased risk.Risk stratification toolA risk stratification tool was compiled using a Caucasian female <50years with no comorbidities as a reference. A point allocated to risk factors associated with an approximate doubling in risk. This tool provides numerical support for healthcare workers when determining which team members should be allocated to patient facing clinical duties compared to remote supportive roles.ConclusionsWe have generated a tool which can provide a framework for objective risk stratification of doctors and health care professionals during the COVID-19 pandemic, without requiring disclosure of information that an individual may not wish to share with their direct line manager during the risk assessment process.Strengths and limitations of this studyThere is an increased risk of mortality in the clinical workforce due to the effects of COVID-19.This manuscript outlines a simple risk stratification tool that helps to quantify an individual’s biological riskThis will assist team leaders when allocating roles within clinical departments.This tool does not incorporate other external factors, such as high-risk household members or those at higher risk of mental health issues, that may require additional consideration when allocating clinical duties in an appropriate clinical domain.This population-based analysis did not explain for the very high risk observed in BAME healthcare workers suggesting there are other issues at play that require addressing.
Abstract.
Strain WD, Paldánius PM (2020). Effect of clinical inertia and trial participation in younger and older adults with diabetes having comorbidities and progressive complications.
Diabetes Research and Clinical Practice,
166Abstract:
Effect of clinical inertia and trial participation in younger and older adults with diabetes having comorbidities and progressive complications
Aim: Clinical inertia is a multifactorial phenomenon, with contributing factors from people with diabetes and their healthcare team. It is widely cited that clinical inertia is minimised by participation in clinical trials. We assessed whether trial participation per se improves metabolic parameters in people with diabetes, or a specific focus on glycaemia is required. Methods: We compared improvement in glycaemic control in a pooled set of people assigned to the “placebo” arm from 25 glycaemia-focused trials with a pooled group of people with diabetes allocated to sham or non-pharmacological intervention for the treatment of diabetic retinal disease. Mean change in HbA1c (ANCOVA) was evaluated. Results: the overall placebo effect in studies focused on glucose control (N = 3081) was comparable between strata groups with and without complications. Adjusted least square mean change in HbA1c at 24 weeks was between −0.23% (−2.50 mmol/mol) and −0.32% (−3.50 mmol/mol). In studies focused on retinal disease (N = 288), the change from baseline in HbA1c was +0.10% (1.10 mmol/mol) and fasting plasma glucose was +0.50 mmol/L showing no improvement in metabolic parameters at 12 months. Conclusions: Clinical trial participation alone does not seem to improve metabolic parameters in people living with diabetes. The benefits observed in glycaemia-focused studies were independent of age and comorbidities.
Abstract.
Williams J, Gilchrist M, Fraser D, Strain D, Shore A (2020). P1161CUTANEOUS MICROCIRCULATORY DYSFUNCTION IN PERITONEAL DIALYSIS PATIENTS. Nephrology Dialysis Transplantation, 35(Supplement_3).
Aizawa K, Casanova F, Mawson D, Gooding K, Elyas S, Adingupu D, Strain D, Gates P, Shore A (2020). P17 Comparisons of Carotid-femoral Pulse Wave Velocity Obtained from the Surface-distance Measurement and from the Population-derived Distance Formula: Associations with Macro- and Microvascular Alterations in Older Adults. Artery Research, 25(Supplement 1).
McKenzie CA, Page VJ, Strain WD, Blackwood B, Ostermann M, Taylor D, Spronk PE, McAuley DF (2020). Parenteral thiamine for prevention and treatment of delirium in critically ill adults: a systematic review protocol.
Syst Rev,
9(1).
Abstract:
Parenteral thiamine for prevention and treatment of delirium in critically ill adults: a systematic review protocol.
BACKGROUND: Delirium is an acute confusional state, common in critical illness and associated with cognitive decline. There is no effective pharmacotherapy to prevent or treat delirium, although it is scientifically plausible that thiamine could be effective. Thiamine studies in dementia patients are inconclusive. Aside from small numbers, all used oral administration: bioavailability of thiamine is poor; parenteral thiamine bypasses this. In the UK, parenteral thiamine is administered as a compound vitamin B and C solution (Pabrinex®). The aim of this review is to evaluate the effectiveness of parenteral thiamine (alone or in a compound solution) in preventing or treating delirium in critical illness. METHODS: We will search for studies in electronic databases (MEDLINE (Pro-Quest), EMBASE, CINAHL, LILACS, CNKI, AMED, and Cochrane CENTRAL), clinical trials registries (WHO International Clinical Trials Registry, ClinicalTrials.gov, and Controlled-trials.com), and grey literature (Google Scholar, conference proceedings, and Index to Theses). We will perform complementary searches of reference lists of included studies, relevant reviews, clinical practice guidelines, or other pertinent documents (e.g. official documents and government reports). We will consider quasi-randomised or randomised controlled trials in critically ill adults. We will include studies that evaluate parenteral thiamine versus standard of care, placebo, or any other non-pharmacological or pharmacological interventions. The primary outcomes will be the delirium core outcome set, including incidence and severity of delirium and cognition. Secondary outcomes are adapted from the ventilation core outcome set: duration of mechanical ventilation, length of stay, and adverse events incidence. Screening, data extraction, and risk of bias assessment will be undertaken independently by two reviewers. If data permits, we will conduct meta-analyses using a random effects model and, where appropriate, sensitivity and subgroup analyses to explore sources of heterogeneity. DISCUSSION: This review will provide evidence for the effectiveness of parental thiamine in the prevention or treatment of delirium in critical care. Findings will contribute to establishing the need for a multicentre study of parenteral thiamine in the prevention and treatment of critical care delirium. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019118808.
Abstract.
Author URL.
Bowman K, Jones L, Masoli J, Mujica-Mota R, Strain D, Butchart J, Valderas JM, Fortinsky RH, Melzer D, Delgado J, et al (2020). Predicting incident delirium diagnoses using data from primary-care electronic health records.
Age Ageing,
49(3), 374-381.
Abstract:
Predicting incident delirium diagnoses using data from primary-care electronic health records.
IMPORTANCE: risk factors for delirium in hospital inpatients are well established, but less is known about whether delirium occurring in the community or during an emergency admission to hospital care might be predicted from routine primary-care records. OBJECTIVES: identify risk factors in primary-care electronic health records (PC-EHR) predictive of delirium occurring in the community or recorded in the initial episode in emergency hospitalisation. Test predictive performance against the cumulative frailty index. DESIGN: Stage 1: case-control; Stages 2 and 3: retrospective cohort. SETTING: clinical practice research datalink: PC-EHR linked to hospital discharge data from England. SUBJECTS: Stage 1: 17,286 patients with delirium aged ≥60 years plus 85,607 controls. Stages 2 and 3: patients ≥ 60 years (n = 429,548 in 2015), split into calibration and validation groups. METHODS: Stage 1: logistic regression to identify associations of 110 candidate risk measures with delirium. Stage 2: calibrating risk factor weights. Stage 3: validation in independent sample using area under the curve (AUC) receiver operating characteristic. RESULTS: fifty-five risk factors were predictive, in domains including: cognitive impairment or mental illness, psychoactive drugs, frailty, infection, hyponatraemia and anticholinergic drugs. The derived model predicted 1-year incident delirium (AUC = 0.867, 0.852:0.881) and mortality (AUC = 0.846, 0.842:0.853), outperforming the frailty index (AUC = 0.761, 0.740:0.782). Individuals with the highest 10% of predicted delirium risk accounted for 55% of incident delirium over 1 year. CONCLUSIONS: a risk factor model for delirium using data in PC-EHR performed well, identifying individuals at risk of new onsets of delirium. This model has potential for supporting preventive interventions.
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Author URL.
Macdougall C, Dangerfield P, Katz D, Strain WD (2020). The impact of COVID-19 on Medical education and Medical Students. How and when can they return to placements?.
MedEdPublish,
9, 159-159.
Abstract:
The impact of COVID-19 on Medical education and Medical Students. How and when can they return to placements?
This article was migrated. The article was marked as recommended. The defining feature of 2020 will be the early and mid-stages of the covid-19 pandemic, declared by the World Health Organisation on 11th March. Rapid worldwide exponential spread continues and by 15 April, more than 1 900 000 cases and 123 000 deaths had been reported worldwide (WHO, 2020).Health services have coped to varying degrees. One common feature has been the withdrawal of routine care (Iacobucci, 2020a) and 'non-essential' staff including learners, although many have returned to undertake care roles. As the likely timeframe for stabilisation of health services becomes clearer, certainly in the United Kingdom (UK) (Iacobucci, 2020b), medical educators need to rapidly get the teaching of the next generation of health care workers back on track if they are to enter health services as confident and competent practitioners in 2020 and 2021.Although a 'whole world' experience, the effects of covid-19 sit in national contexts. We detail the issues for the UK in re-starting and re-inventing medical education, noting that the principles, if not necessarily the detail, will be common across the world.
Abstract.
Albury C, Strain WD, Brocq SL, Logue J, Lloyd C, Tahrani A, Language Matters working group (2020). The importance of language in engagement between health-care professionals and people living with obesity: a joint consensus statement.
Lancet Diabetes Endocrinol,
8(5), 447-455.
Abstract:
The importance of language in engagement between health-care professionals and people living with obesity: a joint consensus statement.
Obesity is a chronic condition that requires long-term management and is associated with unprecedented stigma in different settings, including during interactions with the health-care system. This stigma has a negative effect on the mental and physical health of people with obesity and can lead to avoidance of health care and disruption of the doctor-patient relationship. Considerable evidence exists to suggest that simply having a conversation about obesity can lead to weight loss, which translates into health benefits. However, both health-care practitioners and people living with obesity report apprehension in initiating this conversation. We have collaborated with stakeholders from Obesity UK, physicians, dieticians, clinical psychologists, obesity researchers, conversation analysts, nurses, and representatives from National Health Service England Diabetes and Obesity. This group has contributed to the production of this consensus statement, which addresses how people living with obesity wish to have their condition referred to and provides practical guidance for health-care professionals to facilitate collaborative and supportive discussions about obesity. Expert stakeholders consider that changes to language used at the point of care can alleviate the stigma of obesity within the health-care system and support improved outcomes for both people living with obesity and for the health-care system.
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Author URL.
Williams J, Gilchrist M, Strain D, Fraser D, Shore A (2020). The systemic microcirculation in dialysis populations.
Microcirculation,
27(5).
Abstract:
The systemic microcirculation in dialysis populations.
In a rapidly expanding population of patients with chronic kidney disease, including 2 million people requiring renal replacement therapy, cardiovascular mortality is 15 times greater than the general population. In addition to traditional cardiovascular risk factors, more poorly defined risks related to uremia and its treatments appear to contribute to this exaggerated risk. In this context, the microcirculation may play an important early role in cardiovascular disease associated with chronic kidney disease. Experimentally, the uremic environment and dialysis have been linked to multiple pathways causing microvascular dysfunction. Coronary microvascular dysfunction is reflected in remote and more easily studied vascular beds such as the skin. There is increasing evidence for a correlation between systemic microvascular dysfunction and adverse cardiovascular outcomes. Systemic microcirculatory changes have not been extensively investigated across the spectrum of chronic kidney disease. Recent advances in non-invasive techniques studying the microcirculation in vivo in man are increasing the data available particularly in patients on hemodialysis. Here, we review current knowledge of the systemic microcirculation in dialysis populations, explore whether non-invasive techniques to study its function could be used to detect early stage cardiovascular disease, address challenges faced in studying this patient cohort and identify potential future avenues for research.
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Author URL.
Strain WD, Tsang C, Hurst M, McEwan P, Unadkat M, Meadowcroft S, Shardlow R, Evans M (2020). What Next After Metformin in Type 2 Diabetes? Selecting the Right Drug for the Right Patient.
DIABETES THERAPY,
11(6), 1381-1395.
Author URL.
Strain D, Kar P (2019). 'One-size-fits-all' treatment targets harm frail older patients with diabetes. Clinical Pharmacist, 11(5).
PALDÁNIUS PM, STRAIN WD (2019). 1276-P: Effect of Trial Participation on Metabolic Parameters in People with Progressive Diabetic Complications. Diabetes, 68(Supplement_1).
Masoli J, Correa Delgado J, Bowman K, Strain W, Henley W, Melzer D (2019). Association of blood pressure with clinical outcomes in older adults with chronic kidney disease. Age and Ageing
RESTART Collaboration (2019). Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial.
Lancet,
393(10191), 2613-2623.
Abstract:
Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial.
BACKGROUND: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. METHODS: the REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). FINDINGS: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29-146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0- 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25-1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39-1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65-1·60]; p=0·92). INTERPRETATION: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention. FUNDING: British Heart Foundation.
Abstract.
Author URL.
Al-Shahi Salman R, Minks DP, Mitra D, Rodrigues MA, Bhatnagar P, du Plessis JC, Joshi Y, Dennis MS, Murray GD, Newby DE, et al (2019). Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial.
Lancet Neurol,
18(7), 643-652.
Abstract:
Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial.
BACKGROUND: Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy. METHODS: RESTART was a prospective, randomised, open-label, blinded-endpoint, parallel-group trial at 122 hospitals in the UK that assessed whether starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. For this prespecified subgroup analysis, consultant neuroradiologists masked to treatment allocation reviewed brain CT or MRI scans performed before randomisation to confirm participant eligibility and rate features of the intracerebral haemorrhage and surrounding brain. We followed participants for primary (recurrent symptomatic intracerebral haemorrhage) and secondary (ischaemic stroke) outcomes for up to 5 years (reported elsewhere). For this report, we analysed eligible participants with intracerebral haemorrhage according to their treatment allocation in primary subgroup analyses of cerebral microbleeds on MRI and in exploratory subgroup analyses of other features on CT or MRI. The trial is registered with the ISRCTN registry, number ISRCTN71907627. FINDINGS: Between May 22, 2013, and May 31, 2018, 537 participants were enrolled, of whom 525 (98%) had intracerebral haemorrhage: 507 (97%) were diagnosed on CT (252 assigned to start antiplatelet therapy and 255 assigned to avoid antiplatelet therapy, of whom one withdrew and was not analysed) and 254 (48%) underwent the required brain MRI protocol (122 in the start antiplatelet therapy group and 132 in the avoid antiplatelet therapy group). There were no clinically or statistically significant hazards of antiplatelet therapy on recurrent intracerebral haemorrhage in primary subgroup analyses of cerebral microbleed presence (2 or more) versus absence (0 or 1) (adjusted hazard ratio [HR] 0·30 [95% CI 0·08-1·13] vs 0·77 [0·13-4·61]; pinteraction=0·41), cerebral microbleed number 0-1 versus 2-4 versus 5 or more (HR 0·77 [0·13-4·62] vs 0·32 [0·03-3·66] vs 0·33 [0·07-1·60]; pinteraction=0·75), or cerebral microbleed strictly lobar versus other location (HR 0·52 [0·004-6·79] vs 0·37 [0·09-1·28]; pinteraction=0·85). There was no evidence of heterogeneity in the effects of antiplatelet therapy in any exploratory subgroup analyses (all pinteraction>0·05). INTERPRETATION: Our findings exclude all but a very modest harmful effect of antiplatelet therapy on recurrent intracerebral haemorrhage in the presence of cerebral microbleeds. Further randomised trials are needed to replicate these findings and investigate them with greater precision. FUNDING: British Heart Foundation.
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Author URL.
Dennis M, Mead G, Forbes J, Graham C, Hackett M, Hankey GJ, House A, Lewis S, Lundström E, Sandercock P, et al (2019). Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial.
The Lancet,
393(10168), 265-274.
Abstract:
Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial
Background: Results of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects. Methods: FOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762. Findings: Between Sept 10, 2012, and March 31, 2017, 3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99·3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0·951 [95% CI 0·839–1·079]; p=0·439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13·43%] patients vs 269 [17·21%]; difference 3·78% [95% CI 1·26–6·30]; p=0·0033), but they had more bone fractures (45 [2·88%] vs 23 [1·47%]; difference 1·41% [95% CI 0·38–2·43]; p=0·0070). There were no significant differences in any other event at 6 or 12 months. Interpretation: Fluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function. Funding: UK Stroke Association and NIHR Health Technology Assessment Programme.
Abstract.
Bain SC, Bakhai A, Evans M, Green A, Menown I, Strain WD (2019). Pharmacological treatment for Type 2 diabetes integrating findings from cardiovascular outcome trials: an expert consensus in the UK.
Diabet Med,
36(9), 1063-1071.
Abstract:
Pharmacological treatment for Type 2 diabetes integrating findings from cardiovascular outcome trials: an expert consensus in the UK.
In people with Type 2 diabetes, cardiovascular disease is a leading cause of morbidity and mortality. Thus, as well as controlling glucose, reducing the risk of cardiovascular events is a key goal. The results of cardiovascular outcome trials have led to updates for many national and international guidelines. England, Wales and Northern Ireland remain exceptions, with the most recent update to the National Institute for Health and Care Excellence (NICE) guidelines published in 2015. We reviewed current national and international guidelines and recommendations on the management of people with Type 2 diabetes. This article shares our consensus on clinical recommendations for the use of sodium-glucose co-transporter 2 inhibitors (SGLT-2is) and glucagon-like peptide 1 receptor agonists (GLP-1RAs) in people with Type 2 diabetes and established or at very high risk of cardiovascular disease in the UK. We also consider cost-effectiveness for these therapies. We recommend considering each person's cardiovascular risk and using diabetes therapies with proven cardiovascular benefits when appropriate to improve long-term outcomes and cost-effectiveness.
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Strain WD, McEwan P, Howitt H, Meadowcroft S (2019). Retrospective Database Analysis Evaluating the Clinical Outcomes of Changing Treatment of People with Type 2 Diabetes Mellitus (T2DM) from Other DPP-4 Inhibitor Therapy to Alogliptin in a Primary Care Setting.
Diabetes Ther,
10(4), 1499-1507.
Abstract:
Retrospective Database Analysis Evaluating the Clinical Outcomes of Changing Treatment of People with Type 2 Diabetes Mellitus (T2DM) from Other DPP-4 Inhibitor Therapy to Alogliptin in a Primary Care Setting.
INTRODUCTION: Although some differences between individual dipeptidyl peptidase-4 (DPP-4) inhibitors may exist, the National Institute for Health and Clinical Excellence (NICE) have recommended that 'prescribers should be encouraged to select the individual DPP-4 inhibitor with the lowest acquisition cost available to them, where all other factors are equal'. We aimed to determine whether or not 'within class' switching to alogliptin, the DPP-4 inhibitor with lowest acquisition cost, is a clinically appropriate strategy. METHODS: This study evaluated people with type 2 diabetes taking DPP-4 inhibitor therapy in addition to at least one other diabetes therapy. Primary care records were reviewed from six clinical commissioning groups (CCGs). For people who had been switched from other DPP-4 inhibitors to alogliptin, an assessment of the impact of switch on both absolute haemoglobin A1c (HbA1c) levels and on HbA1c trajectory was undertaken. Persistence on alogliptin and the need for therapy intensification was also assessed. RESULTS: Overall, 865 people with diabetes met the eligibility criteria for the study. There was no significant difference between pre- and post-switch mean HbA1c level [8.44% (SD 1.52%) vs 8.42% (1.62%), p = 0.6]. Similarly, for patients where there was sufficient data to assess the impact of switching on HbA1c trajectory (n = 319) minimal impact was identified (actual HbA1c at 3 months 8.33% vs projected 8.31%). The majority of people with diabetes (80.76%) remained on alogliptin treatment at 6 months and only 4.54% required additional diabetes therapies. Switching to alogliptin resulted in a median saving of £7.24 per patient-month. CONCLUSION: Switching United Kingdom (UK) primary care patients from other DPP-4 inhibitors to alogliptin did not result in a statistically significant or clinically meaningful change in HbA1c level and few required the addition of further diabetes therapies, suggesting that therapy change or intensification was not considered necessary in most patients who were switched to alogliptin. TRIAL REGISTRATION: ENCePP clinical trial registration number EUPAS29153. FUNDING: Takeda UK Ltd.
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van Zuydam NR, Ahlqvist E, Sandholm N, Deshmukh H, Rayner NW, Abdalla M, Ladenvall C, Ziemek D, Fauman E, Robertson NR, et al (2018). A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects with Type 2 Diabetes.
Diabetes,
67(7), 1414-1427.
Abstract:
A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects with Type 2 Diabetes.
Identification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 × 10-8) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.
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Author URL.
Strain WD, Paldánius PM (2018). Diabetes, cardiovascular disease and the microcirculation.
Cardiovasc Diabetol,
17(1).
Abstract:
Diabetes, cardiovascular disease and the microcirculation.
Cardiovascular disease (CVD) is the leading cause of mortality in people with type 2 diabetes mellitus (T2DM), yet a significant proportion of the disease burden cannot be accounted for by conventional cardiovascular risk factors. Hypertension occurs in majority of people with T2DM, which is substantially more frequent than would be anticipated based on general population samples. The impact of hypertension is considerably higher in people with diabetes than it is in the general population, suggesting either an increased sensitivity to its effect or a confounding underlying aetiopathogenic mechanism of hypertension associated with CVD within diabetes. In this contribution, we aim to review the changes observed in the vascular tree in people with T2DM compared to the general population, the effects of established anti-diabetes drugs on microvascular outcomes, and explore the hypotheses to account for common causalities of the increased prevalence of CVD and hypertension in people with T2DM.
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Author URL.
Gates PE, Gurung A, Mazzaro L, Aizawa K, Elyas S, Strain WD, Shore AC, Shandas R (2018). Measurement of Wall Shear Stress Exerted by Flowing Blood in the Human Carotid Artery: Ultrasound Doppler Velocimetry and Echo Particle Image Velocimetry.
Ultrasound Med Biol,
44(7), 1392-1401.
Abstract:
Measurement of Wall Shear Stress Exerted by Flowing Blood in the Human Carotid Artery: Ultrasound Doppler Velocimetry and Echo Particle Image Velocimetry.
Vascular endothelial cells lining the arteries are sensitive to wall shear stress (WSS) exerted by flowing blood. An important component of the pathophysiology of vascular diseases, WSS is commonly estimated by centerline ultrasound Doppler velocimetry (UDV). However, the accuracy of this method is uncertain. We have previously validated the use of a novel, ultrasound-based, particle image velocimetry technique (echo PIV) to compute 2-D velocity vector fields, which can easily be converted into WSS data. We compared WSS data derived from UDV and echo PIV in the common carotid artery of 27 healthy participants. Compared with echo PIV, time-averaged WSS was lower using UDV (28 ± 35%). Echo PIV revealed that this was due to considerable spatiotemporal variation in the flow velocity profile, contrary to the assumption that flow is steady and the velocity profile is parabolic throughout the cardiac cycle. The largest WSS underestimation by UDV was found during peak systole (118 ± 16%) and the smallest during mid-diastole (4.3± 46%). The UDV method underestimated WSS for the accelerating and decelerating systolic measurements (68 ± 30% and 24 ± 51%), whereas WSS was overestimated for end-diastolic measurements (-44 ± 55%). Our data indicate that UDV estimates of WSS provided limited and largely inaccurate information about WSS and that the complex spatiotemporal flow patterns do not fit well with traditional assumptions about blood flow in arteries. Echo PIV-derived WSS provides detailed information about this important but poorly understood stimulus that influences vascular endothelial pathophysiology.
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Author URL.
Zirk-Sadowski J, Masoli JA, Delgado J, Hamilton W, Strain WD, Henley W, Melzer D, Ble A (2018). Proton-Pump Inhibitors and Long-Term Risk of Community-Acquired Pneumonia in Older Adults.
J Am Geriatr Soc,
66(7), 1332-1338.
Abstract:
Proton-Pump Inhibitors and Long-Term Risk of Community-Acquired Pneumonia in Older Adults.
OBJECTIVES: to estimate associations between long-term use of proton pump inhibitors (PPIs) and pneumonia incidence in older adults in primary care. DESIGN: Longitudinal analyses of electronic medical records. SETTING: England PARTICIPANTS: Individuals aged 60 and older in primary care receiving PPIs for 1 year or longer (N=75,050) and age- and sex-matched controls (N=75,050). MEASUREMENTS: Net hazard ratios for pneumonia incidence in Year 2 of treatment were estimated using the prior event rate ratio (PERR), which adjusts for pneumonia incidence differences before initiation of treatment. Inverse probability weighted models adjusted for 78 demographic, disease, medication, and healthcare usage measures. RESULTS: During the second year after initiating treatment, PPIs were associated with greater hazard of incident pneumonia (PERR-adjusted hazard ratio=1.82, 95% confidence interval=1.27-2.54), accounting for pretreatment pneumonia rates. Estimates were similar across age and comorbidity subgroups. Similar results were also obtained from propensity score- and inverse probability-weighted models. CONCLUSION: in a large cohort of older adults in primary care, PPI prescription was associated with greater risk of pneumonia in the second year of treatment. Results were robust across alternative analysis approaches. Controversies about the validity of reported short-term harms of PPIs should not divert attention from potential long-term effects of PPI prescriptions on older adults.
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Author URL.
Aizawa K, Casanova F, Mawson DM, Gooding KM, Strain WD, Gates PE, Östling G, Khan F, Colhoun HM, Palombo C, et al (2018). Reservoir pressure integral is independently associated with the reduction in renal function in an older population. Artery Research, 24(C), 72-73.
Soto C, Strain WD (2018). Tackling clinical inertia: Use of coproduction to improve patient engagement.
J Diabetes,
10(12), 942-947.
Abstract:
Tackling clinical inertia: Use of coproduction to improve patient engagement.
Clinical inertia is common in all chronic diseases, including diabetes. Despite the advent of newer agents for the management of hyperglycemia, hypertension, and dyslipidemia, the number of people with diabetes hitting all three targets remains small. The causes of clinical inertia are multifactorial, with contributory elements from people with diabetes, physicians, and the system within which they work. Every health care provider should have the best interest of their patients at heart; most people with diabetes want to maintain their health for as long as possible, and the maintenance of good health is not only the purpose of the system, but also the most cost-effective strategy. It is the thesis of this article that a potential reversible contributor to clinical inertia is the communication among these individual elements, which can be called "coproduction." the coproduction model of open communication encourages discourse, allowing the person with diabetes to understand their diagnosis and therefore better engage in treatment options. Improving engagement allows the healthcare team, including the physician and the person with diabetes, to establish shared goals that are important to all team members and to agree to acceptable side effects or risks of interventions in order to achieve these goals. Everyone needs to acknowledge that non-adherence exists and can be an issue, thereby allowing reasons to be explored. Only once the person with diabetes is allowed to take full ownership of their disease and actively participate in decision making can they take control of their disease, thereby improving outcomes.
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Author URL.
Al-Shahi Salman R, Dennis MS, Murray GD, Innes K, Drever J, Dinsmore L, Williams C, White PM, Whiteley WN, Sandercock PAG, et al (2018). The REstart or STop Antithrombotics Randomised Trial (RESTART) after stroke due to intracerebral haemorrhage: Study protocol for a randomised controlled trial.
Trials,
19(1).
Abstract:
The REstart or STop Antithrombotics Randomised Trial (RESTART) after stroke due to intracerebral haemorrhage: Study protocol for a randomised controlled trial
Background: for adults surviving stroke due to spontaneous (non-traumatic) intracerebral haemorrhage (ICH) who had taken an antithrombotic (i.e. anticoagulant or antiplatelet) drug for the prevention of vaso-occlusive disease before the ICH, it is unclear whether starting antiplatelet drugs results in an increase in the risk of recurrent ICH or a beneficial net reduction of all serious vascular events compared to avoiding antiplatelet drugs. Methods/design: the REstart or STop Antithrombotics Randomised Trial (RESTART) is an investigator-led, randomised, open, assessor-blind, parallel-group, randomised trial comparing starting versus avoiding antiplatelet drugs for adults surviving antithrombotic-associated ICH at 122 hospital sites in the United Kingdom. RESTART uses a central, web-based randomisation system using a minimisation algorithm, with 1:1 treatment allocation to which central research staff are masked. Central follow-up includes annual postal or telephone questionnaires to participants and their general (family) practitioners, with local provision of information about adverse events and outcome events. The primary outcome is recurrent symptomatic ICH. The secondary outcomes are: symptomatic haemorrhagic events; symptomatic vaso-occlusive events; symptomatic stroke of uncertain type; other fatal events; modified Rankin Scale score; adherence to antiplatelet drug(s). The magnetic resonance imaging (MRI) sub-study involves the conduct of brain MRI according to a standardised imaging protocol before randomisation to investigate heterogeneity of treatment effect according to the presence of brain microbleeds. Recruitment began on 22 May 2013. The target sample size is at least 720 participants in the main trial (at least 550 in the MRI sub-study). Discussion: Final results of RESTART will be analysed and disseminated in 2019.
Abstract.
Strain WD, Hope SV, Green A, Kar P, Valabhji J, Sinclair AJ (2018). Type 2 diabetes mellitus in older people: a brief statement of key principles of modern day management including the assessment of frailty. A national collaborative stakeholder initiative.
Diabet Med,
35(7), 838-845.
Abstract:
Type 2 diabetes mellitus in older people: a brief statement of key principles of modern day management including the assessment of frailty. A national collaborative stakeholder initiative.
Rates of population ageing are unprecedented and this, combined with the progressive urbanization of lifestyles, has led to a dramatic shift in the epidemiology of diabetes towards old age, particularly to those aged 60-79 years. Both ageing and diabetes are recognized as important risk factors for the development of functional decline and disability. In addition, diabetes is associated with a high economic, social and health burden. Traditional macrovascular and microvascular complications of diabetes appear to account for less than half of the diabetes-related disability observed in older people. Despite this, older adults are under-represented in clinical trials. Guidelines from organizations such as the National Institute for Health and Care Excellence (NICE), the European Association for the Study of Diabetes, and the American Diabetes Association acknowledge the need for individualized care, but the glycaemic targets that are suggested to constitute good control [HbA1c 53-59 mmol/mol (7-7.5%)] are too tight for frail older individuals. We present a framework for the assessment of older adults and guidelines for the management of this population according to their frailty status, with the intention of reducing complications and improving quality of life for these people.
Abstract.
Author URL.
Meertens RM, Casanova F, Knapp KM, Thorn C, Strain WD (2018). Use of Near-Infrared Systems for Investigations of Hemodynamics in Human in Vivo Bone Tissue: a Systematic Review. Journal of Orthopaedic Research
Strain WD, Cos X, Prünte C (2017). Considerations for management of patients with diabetic macular edema: Optimizing treatment outcomes and minimizing safety concerns through interdisciplinary collaboration.
Diabetes Res Clin Pract,
126, 1-9.
Abstract:
Considerations for management of patients with diabetic macular edema: Optimizing treatment outcomes and minimizing safety concerns through interdisciplinary collaboration.
Diabetes is a growing worldwide epidemic and a leading cause of blindness in working-age people around the world. Diabetic retinopathy (DR) and diabetic macular edema (DME) are common causes of visual impairment in people with diabetes and often indicate the presence of diabetes-associated preclinical micro- and macrovascular complications. As such, patients with DR and DME often display complex, highly comorbid profiles. Several treatments are currently available for the treatment of DME, including anti-vascular endothelial growth factor (VEGF) agents, which are administered via intravitreal injection. While the safety profiles of approved ocular anti-VEGF therapies have been reassuring, the high-risk nature of the DME patient population means that treatment must be carefully considered and a holistic approach to disease management should be taken. This requires multidisciplinary, collaborative care involving all relevant specialties to ensure that patients not only receive prompt treatment for DME but also appropriate consideration is taken of any systemic comorbidities to evaluate and minimize potentially serious safety issues.
Abstract.
Author URL.
Strain WD, Paldánius PM (2017). Dipeptidyl Peptidase-4 Inhibitor Development and Post-authorisation Programme for Vildagliptin – Clinical Evidence for Optimised Management of Chronic Diseases Beyond Type 2 Diabetes.
European Endocrinology,
13(02), 62-62.
Abstract:
Dipeptidyl Peptidase-4 Inhibitor Development and Post-authorisation Programme for Vildagliptin – Clinical Evidence for Optimised Management of Chronic Diseases Beyond Type 2 Diabetes
The last decade has witnessed the role of dipeptidyl peptidase-4 (DPP-4) inhibitors in producing a conceptual change in early management of type 2 diabetes mellitus (T2DM) by shifting emphasis from a gluco-centric approach to holistically treating underlying pathophysiological processes. DPP-4 inhibitors highlighted the importance of acknowledging hypoglycaemia and weight gain as barriers to optimised care in T2DM. These complications were an integral part of diabetes management before the introduction of DPP-4 inhibitors. During the development of DPP-4 inhibitors, regulatory requirements for introducing new agents underwent substantial changes, with increased emphasis on safety. This led to the systematic collection of adjudicated cardiovascular (CV) safety data, and, where 95% confidence of a lack of harm could not be demonstrated, the standardised CV safety studies. Furthermore, the growing awareness of the worldwide extent of T2DM demanded a more diverse approach to recruitment and participation in clinical trials. Finally, the global financial crisis placed a new awareness on the health economics of diabetes, which rapidly became the most expensive disease in the world. This review encompasses unique developments in the global landscape, and the role DPP-4 inhibitors, specifically vildagliptin, have played in research advancement and optimisation of diabetes care in a diverse population with T2DM worldwide.
Abstract.
Gurung A, Gates PE, Mazzaro L, Fulford J, Zhang F, Barker AJ, Hertzberg J, Aizawa K, Strain WD, Elyas S, et al (2017). Echo Particle Image Velocimetry for Estimation of Carotid Artery Wall Shear Stress: Repeatability, Reproducibility and Comparison with Phase-Contrast Magnetic Resonance Imaging.
Ultrasound Med Biol,
43(8), 1618-1627.
Abstract:
Echo Particle Image Velocimetry for Estimation of Carotid Artery Wall Shear Stress: Repeatability, Reproducibility and Comparison with Phase-Contrast Magnetic Resonance Imaging.
Measurement of hemodynamic wall shear stress (WSS) is important in investigating the role of WSS in the initiation and progression of atherosclerosis. Echo particle image velocimetry (echo PIV) is a novel ultrasound-based technique for measuring WSS in vivo that has previously been validated in vitro using the standard optical PIV technique. We evaluated the repeatability and reproducibility of echo PIV for measuring WSS in the human common carotid artery. We measured WSS in 28 healthy participants (18 males and 10 females, mean age: 56 ± 12 y). Echo PIV was highly repeatable, with an intra-observer variability of 1.0 ± 0.1 dyn/cm2 for peak systolic (maximum), 0.9 dyn/cm2 for mean and 0.5 dyn/cm2 for end-diastolic (minimum) WSS measurements. Likewise, echo PIV was reproducible, with a low inter-observer variability (max: 2.0 ± 0.2 dyn/cm2, mean: 1.3 ± 0.1 dyn/cm2, end-diastolic: 0.7 dyn/cm2) and more variable inter-scan (test-retest) variability (max: 7.1 ± 2.3 dyn/cm2, mean: 2.9 ± 0.4 dyn/cm2, min: 1.5 ± 0.1 dyn/cm2). We compared echo PIV with the reference method, phase-contrast magnetic resonance imaging (PC-MRI); echo PIV-based WSS measurements agreed qualitatively with PC-MRI measurements (r = 0.89, p
Abstract.
Author URL.
strain WD, Abhijit A, Paldanius PM (2017). Individualizing treatment targets for elderly patients with type 2 diabetes: factors influencing clinical decision making in the 24-week, randomized INTERVAL study. Aging
Hope SV, Knight BA, Shields BM, Hill AV, Choudhary P, Strain WD, McDonald TJ, Jones AG (2017). Random non-fasting C-peptide testing can identify patients with insulin-treated type 2 diabetes at high risk of hypoglycaemia. Diabetologia
Ziemssen F, Cruess A, Dunger-Baldauf C, Margaron P, Snow H, Strain WD (2017). Ranibizumab in Diabetic Macular Oedema – a Benefit–risk Analysis of Ranibizumab 0.5 mg PRN Versus Laser Treatment.
European Endocrinology,
13(02), 91-91.
Abstract:
Ranibizumab in Diabetic Macular Oedema – a Benefit–risk Analysis of Ranibizumab 0.5 mg PRN Versus Laser Treatment
Introduction: the structured Benefit–risk Action Team (BRAT) approach aims to assist healthcare decision makers in treatment assessments. We applied BRAT to compare the benefit–risk profile of ranibizumab 0.5 mg versus laser photocoagulation for the treatment of diabetic macular oedema (DMO). Methods: One-year data for the ranibizumab 0.5 mg pro re nata (PRN) and laser arms of the phase III trials RESPOND (NCT01135914; n=220), RESTORE (NCT00687804; n=345), and REVEAL (NCT00989989; n=396) were included in the analysis. The benefit measures included ≥10 letters gain/avoidance of loss in best-corrected visual acuity (BCVA), achieving central retinal thickness (CRT) <275 μm, and 25-item Visual Function Questionnaire (VFQ-25) outcomes. The risks measures included endophthalmitis, intraocular pressure increase, hypertension, proteinuria, arterial/venous thromboembolic events and deaths. Results: Ranibizumab treatment provided significant benefits compared with laser for ≥10 letter BCVA gain at month 12 (387/1,000 versus 152/1,000 patients), CRT <275 μm at 12 months (474/1,000 versus 348/1,000 patients), and improvement of ≥6.06 on the VFQ-25 near activities subscale (325/1,000 versus 245/1,000 patients). Results for the risk measures were similar for both treatments. Conclusions: Superior clinically relevant outcomes were observed with ranibizumab 0.5 mg PRN compared with laser without compromising on safety. This analysis further supports the positive benefit–risk profile of ranibizumab 0.5 mg PRN.
Abstract.
Epstein KA, Viscoli CM, Spence JD, Young LH, Inzucchi SE, Gorman M, Gerstenhaber B, Guarino PD, Dixit A, Furie KL, et al (2017). Smoking cessation and outcome after ischemic stroke or TIA.
Neurology,
89(16), 1723-1729.
Abstract:
Smoking cessation and outcome after ischemic stroke or TIA.
OBJECTIVE: to assess whether smoking cessation after an ischemic stroke or TIA improves outcomes compared to continued smoking. METHODS: We conducted a prospective observational cohort study of 3,876 nondiabetic men and women enrolled in the Insulin Resistance Intervention After Stroke (IRIS) trial who were randomized to pioglitazone or placebo within 180 days of a qualifying stroke or TIA and followed up for a median of 4.8 years. A tobacco use history was obtained at baseline and updated during annual interviews. The primary outcome, which was not prespecified in the IRIS protocol, was recurrent stroke, myocardial infarction (MI), or death. Cox regression models were used to assess the differences in stroke, MI, and death after 4.8 years, with correction for adjustment variables prespecified in the IRIS trial: age, sex, stroke (vs TIA) as index event, history of stroke, history of hypertension, history of coronary artery disease, and systolic and diastolic blood pressures. RESULTS: at the time of their index event, 1,072 (28%) patients were current smokers. By the time of randomization, 450 (42%) patients had quit smoking. Among quitters, the 5-year risk of stroke, MI, or death was 15.7% compared to 22.6% for patients who continued to smoke (adjusted hazard ratio 0.66, 95% confidence interval 0.48-0.90). CONCLUSION: Cessation of cigarette smoking after an ischemic stroke or TIA was associated with significant health benefits over 4.8 years in the IRIS trial cohort.
Abstract.
Author URL.
Casanova F, Adingupu DD, Adams F, Gooding KM, Looker HC, Aizawa K, Dove F, Elyas S, Belch JJF, Gates PE, et al (2017). The impact of cardiovascular co-morbidities and duration of diabetes on the association between microvascular function and glycaemic control.
Cardiovasc Diabetol,
16(1).
Abstract:
The impact of cardiovascular co-morbidities and duration of diabetes on the association between microvascular function and glycaemic control.
BACKGROUND: Good glycaemic control in type 2 diabetes (T2DM) protects the microcirculation. Current guidelines suggest glycaemic targets be relaxed in advanced diabetes. We explored whether disease duration or pre-existing macrovascular complications attenuated the association between hyperglycaemia and microvascular function. METHODS: 743 participants with T2DM (n = 222), cardiovascular disease (CVD = 183), both (n = 177) or neither (controls = 161) from two centres in the UK, underwent standard clinical measures and endothelial dependent (ACh) and independent (SNP) microvascular function assessment using laser Doppler imaging. RESULTS: People with T2DM and CVD had attenuated ACh and SNP responses compared to controls. This was additive in those with both (ANOVA p
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Author URL.
Vencio S, Paldánius PM, Blüher M, Giannella-Neto D, Caiado-Vencio R, Strain WD (2017). Understanding the barriers and improving care in type 2 diabetes: Brazilian perspective in time to do more in diabetes.
Diabetology and Metabolic Syndrome,
9(1).
Abstract:
Understanding the barriers and improving care in type 2 diabetes: Brazilian perspective in time to do more in diabetes
Background: Type 2 diabetes mellitus (T2DM) is a complex disease, particularly in a continental country like Brazil. We attempted to understand and evaluate the perceptions and routines of Brazilians with T2DM and physicians, compared with other countries. Methods: We compared the results from a 20-min online survey in Brazil with simultaneously collated data from India, Japan, Spain, UK and USA. Results: in total, 652 adults with T2DM and 337 treating physicians were enrolled, of whom 100 patients and 55 physicians were from Brazil. The numbers of primary care physicians from the five countries were 221 versus 43 in Brazil, diabetes specialists were 61 versus 12. There was disconnect between the opinions of physicians and people with diabetes globally. Further, there were differences between clinical practices in Brazil versus the rest of the world, in many areas Brazilians were performing better. Conclusions: Communication between patients and physicians should be clearer. There is an urgent need to identify the deficits in education, in order to address the clinical inertia within the diabetes management team. There is a necessity to understand the specific requirements of the Brazilian population in order to contextualise international guidelines and implement local changes in practice.
Abstract.
Strain WD, Smith C (2016). Cardiovascular Outcome Studies in Diabetes: How Do We Make Sense of These New Data?.
Diabetes Ther,
7(2), 175-185.
Abstract:
Cardiovascular Outcome Studies in Diabetes: How Do We Make Sense of These New Data?
Poorly controlled diabetes is characterized by premature cardiovascular mortality and morbidity. The mechanisms linking hyperglycemia with accelerated atherosclerotic disease have not been fully elucidated; however, are thought to be mediated through vascular inflammation, oxidative stress and endothelial dysfunction. The advent of incretin-based therapy, whether by increasing endogenous glucagon-like peptide (GLP)-1 and glucose-dependent inhibitory polypeptide by inhibition of their breakdown using di-peptidyl peptidase 4 inhibitors, or augmenting GLP-1 activity using either exendin-4-based drugs or synthetic GLP-1 analogs promised not just improvements in glycemic control, but improvements in endothelial function, lipid profiles and markers of vascular inflammation. As such, it was anticipated they would demonstrate cardiovascular benefit in those with diabetes, indeed early meta-analyses suggested cardiovascular events would be reduced. To date, however, this benefit has failed to materialize, indeed the cardiovascular outcome trials, whilst meeting their primary endpoint of cardiovascular safety, have failed to demonstrate any improvements in stroke or myocardial infarction. This review will explore the data and attempt to answer the question: what went wrong?
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Author URL.
Aizawa K, Elyas S, Adingupu DD, Casanova F, Gooding KM, Shore AC, Strain WD, Gates PE (2016). Echogenicity of the Common Carotid Artery Intima-Media Complex in Stroke.
Ultrasound Med Biol,
42(5), 1130-1137.
Abstract:
Echogenicity of the Common Carotid Artery Intima-Media Complex in Stroke.
The grey-scale median of the common carotid artery intima-media complex (IM-GSM) characterizes arterial wall composition, and a low IM-GSM is associated with increased cardiovascular mortality in the elderly. We aimed to determine differences in the IM-GSM between a cohort with cerebrovascular disease and a healthy cohort. Eighty-two healthy individuals (control group: 63.2 ± 8.7 y) and 96 patients with either stroke or transient ischemic attacks (CRVD group: 68.6 ± 9.8 y) were studied. Common carotid artery intima-media thickness and IM-GSM obtained by ultrasound were analyzed using semi-automated edge-detection software. The IM-GSM was significantly lower in the CRVD group than in the control group (106 ± 24 vs. 124 ± 27 au, p < 0.001). The IM-GSM was similar for the infarct and non-infarct sides in CRVD. In the pooled cohort of all participants, the lower the quartile of IM-GSM, the greater were the carotid artery intima-media thickness and carotid artery remodeling. These results suggest the presence of an altered atherosclerotic phenotype in the intima-media complex of CRVD patients that can be detected by ultrasound.
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Author URL.
Williams J, Gilchrist M, Strain D (2016). Glucose dysregulation and its effect on peritoneal dialysis patients. Journal of Kidney Care, 1(2), 58-61.
Elyas S, Shore AC, Kingwell H, Keenan S, Boxall L, Stewart J, James MA, Strain WD (2016). Microalbuminuria could improve risk stratification in patients with TIA and minor stroke.
Ann Clin Transl Neurol,
3(9), 678-683.
Abstract:
Microalbuminuria could improve risk stratification in patients with TIA and minor stroke.
OBJECTIVE: Transient ischemic attacks (TIA) and minor strokes are important risk factors for recurrent strokes. Current stroke risk prediction scores such as ABCD2, although widely used, lack optimal sensitivity and specificity. Elevated urinary albumin excretion predicts cardiovascular disease, stroke, and mortality. We explored the role of microalbuminuria (using albumin creatinine ratio (ACR)) in predicting recurrence risk in patients with TIA and minor stroke. METHODS: Urinary ACR was measured on a spot sample in 150 patients attending a daily stroke clinic with TIA or minor stroke. Patients were followed up at day 7, 30, and 90 to determine recurrent stroke, cardiovascular events, or death. Eligible patients had a carotid ultrasound Doppler investigation. High-risk patients were defined as those who had an event within 90 days or had >50% internal carotid artery (ICA) stenosis. RESULTS: Fourteen (9.8%) recurrent events were reported by day 90 including two deaths. Fifteen patients had severe ICA stenosis. In total, 26 patients were identified as high risk. These patients had a higher frequency of previous stroke or hypercholesterolemia compared to low-risk patients (P = 0.04). ACR was higher in high-risk patients (3.4 [95% CI 2.2-5.2] vs. 1.7 [1.5-2.1] mg/mmol, P = 0.004), independent of age, sex, blood pressure, diabetes, and previous stroke. An ACR greater than 1.5 mg/mmol predicted high-risk patients (Cox proportional hazard ratio 3.5 (95% CI 1.3-9.5, P = 0.01). INTERPRETATION: After TIA or minor stroke, a higher ACR predicted recurrent events and significant ICA stenosis. Incorporation of urinary ACR from a spot sample in the acute setting could improve risk stratification in patients with TIA and minor stroke.
Abstract.
Author URL.
Delgado J, Masoli JAH, Bowman K, Strain WD, Kuchel GA, Walters K, Lafortune L, Brayne C, Melzer D, Ble A, et al (2016). Outcomes of Treated Hypertension at Age 80 and Older: Cohort Analysis of 79,376 Individuals.
Journal of the American Geriatrics Society,
65(5), 995-1003.
Abstract:
Outcomes of Treated Hypertension at Age 80 and Older: Cohort Analysis of 79,376 Individuals
© 2016 the Authors. The Journal of the American Geriatrics Society published by Wiley Periodicals, Inc. on behalf of the American Geriatrics Society. Objectives: to estimate outcomes according to attained blood pressure (BP) in the oldest adults treated for hypertension in routine family practice. Design: Cohort analysis of primary care inpatient and death certificate data for individuals with hypertension. Setting: Primary care practices in England (Clinical Practice Research Datalink). Participants: Individuals aged 80 and older taking antihypertensive medication and free of dementia, cancer, coronary heart disease, stroke, heart failure, and end-stage renal failure at baseline. Measurements: Outcomes were mortality, cardiovascular events, and fragility fractures. Systolic BP (SBP) was grouped in 10-mmHg increments from less than 125 to 185 mmHg or more (reference 145–154 mmHg). Results: Myocardial infarction hazards increased linearly with increasing SBP, and stroke hazards increased for SBP of 145 mmHg or greater, although lowest mortality was in individuals with SBP of 135 to 154 mmHg. Mortality of the 13.1% of patients with SBP less than 135 mmHg was higher than that of the reference group (Cox hazard ratio=1.25, 95% confidence interval=1.19–1.31; equating to one extra death per 12.6 participants). This difference in mortality was consistent over short- and long-term follow-up; adjusting for diastolic BP did not change the risk. Incident heart failure rates were higher in those with SBP less than 125 mmHg than in the reference group. Conclusion: in routine primary care, SBP less than 135 mmHg was associated with greater mortality in the oldest adults with hypertension and free of selected potentially confounding comorbidities. Although important confounders were accounted for, observational studies cannot exclude residual confounding. More work is needed to establish whether unplanned SBPs less than 135 mmHg in older adults with hypertension may be a useful clinical sign of poor prognosis, perhaps requiring clinical review of overall care.
Abstract.
Kernan WN, Viscoli CM, Furie KL, Young LH, Inzucchi SE, Gorman M, Guarino PD, Lovejoy AM, Peduzzi PN, Conwit R, et al (2016). Pioglitazone after Ischemic Stroke or Transient Ischemic Attack. New England Journal of Medicine, 374(14), 1321-1331.
Aizawa K, Elyas S, Adingupu DD, Casanova F, Gooding KM, Strain WD, Shore AC, Gates PE (2016). Reactivity to low-flow as a potential determinant for brachial artery flow-mediated vasodilatation.
Physiol Rep,
4(12).
Abstract:
Reactivity to low-flow as a potential determinant for brachial artery flow-mediated vasodilatation.
Previous studies have reported a vasoconstrictor response in the radial artery during a cuff-induced low-flow condition, but a similar low-flow condition in the brachial artery results in nonuniform reactivity. This variable reactivity to low-flow influences the subsequent flow-mediated dilatation (FMD) response following cuff-release. However, it is uncertain whether reactivity to low-flow is important in data interpretation in clinical populations and older adults. This study aimed to determine the influence of reactivity to low-flow on the magnitude of brachial artery FMD response in middle-aged and older individuals with diverse cardiovascular risk profiles. Data were analyzed from 165 individuals, divided into increased cardiovascular risk (CVR: n = 115, 85M, 67.0 ± 8.8 years) and healthy control (CTRL: n = 50, 30M, 63.2 ± 7.2 years) groups. Brachial artery diameter and blood velocity data obtained from Doppler ultrasound were used to calculate FMD, reactivity to low-flow and estimated shear rate (SR) using semiautomated edge-detection software. There was a significant association between reactivity to low-flow and FMD in overall (r = 0.261), CTRL (r = 0.410) and CVR (r = 0.189, all P
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Author URL.
Meertens RM, Knapp KM, Strain WD, Casanova F (2016). The Effects of Lumbar Sympathectomy on Bone and Soft Tissue Haemodynamics of the Leg recorded using Near Infrared Spectroscopy: a Case Report. Journal of Biomedical Engineering and Informatics, 3, 28-32.
Aizawa K, Casanova F, Mawson D, Elyas S, Adingupu DD, Gooding KM, Strain WD, Park CM, Parker KH, Gates PE, et al (2016). [PP.11.05] RESERVOIR-PRESSURE ANALYSIS IN TYPE 2 DIABETES INDIVIDUALS WITH CARDIOVASCULAR DISEASE. Journal of Hypertension, 34(Supplement 2), e178-e178.
Jones LC, Strain WD, Sword J, Ostrowski C (2015). 53. THE CORRELATION BETWEEN PATIENTS, PATIENT'S RELATIVES AND HEALTHCARE PROFESSIONALS INTERPRETATION OF QUALITY OF LIFE - a PROSPECTIVE STUDY. Age and Ageing, 44(suppl 1), i16-i16.
Meertens RM, Strain WD, Knapp KM (2015). A Review of the Mechanisms, Diagnosis and Preventative Treatment of Osteoporotic Fragility Fractures in Patients with Type 2 Diabetes Mellitus.
Journal of Endocrinology and Metabolism,
Volume 5(Number 1-2), 157-162.
Abstract:
A Review of the Mechanisms, Diagnosis and Preventative Treatment of Osteoporotic Fragility Fractures in Patients with Type 2 Diabetes Mellitus
The primary association of both type 2 diabetes mellitus (T2DM) and fragility fractures with age has become cause for concern in the developed world, with T2DM now considered an independent risk factor for an increased risk of fragility fracture. The increased susceptibility to fragility fracture associated with T2DM has wide ranging and increasing socioeconomic, morbidity and mortality effects. As the incidence of T2DM increases, understanding the mechanisms behind why T2DM is a causative risk factor to decreased bone health is an important step. These may be split into two broad categories: those that involve an increased risk of falling, and those mechanisms that make fragility fracture after falling more likely due to detrimental changes to bone strength. The latter is not definitively understood making diagnosis in T2DM populations difficult. Current diagnostic methods do not sufficiently account for the unique endocrinological effects of T2DM on bone. New markers for identifying fragility fracture risk in patients with T2DM are required to overcome the paradoxical increase in bone mineral density (BMD) in these populations, and the shortcomings of predictive algorithms and dual energy X-ray absorptiometry (DXA) in identifying fracture risk in T2DM populations. Earlier identification of patients with T2DM who are at risk of fragility fracture is important, as these patients are not as responsive to current preventative medical interventions as those without T2DM, although there are also adoptive lifestyle changes that can help.
Abstract.
Packer M, McMurray JJV, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, et al (2015). Angiotensin Receptor Neprilysin Inhibition Compared with Enalapril on the Risk of Clinical Progression in Surviving Patients with Heart Failure.
Circulation,
131(1), 54-61.
Abstract:
Angiotensin Receptor Neprilysin Inhibition Compared with Enalapril on the Risk of Clinical Progression in Surviving Patients with Heart Failure
. Background—
. Clinical trials in heart failure have focused on the improvement in symptoms or decreases in the risk of death and other cardiovascular events. Little is known about the effect of drugs on the risk of clinical deterioration in surviving patients.
.
.
. Methods and Results—
.
. We compared the angiotensin-neprilysin inhibitor LCZ696 (400 mg daily) with the angiotensin-converting enzyme inhibitor enalapril (20 mg daily) in 8399 patients with heart failure and reduced ejection fraction in a double-blind trial. The analyses focused on prespecified measures of nonfatal clinical deterioration. In comparison with the enalapril group, fewer LCZ696-treated patients required intensification of medical treatment for heart failure (520 versus 604; hazard ratio, 0.84; 95% confidence interval, 0.74–0.94;
. P
. =0.003) or an emergency department visit for worsening heart failure (hazard ratio, 0.66; 95% confidence interval, 0.52–0.85;
. P
. =0.001). The patients in the LCZ696 group had 23% fewer hospitalizations for worsening heart failure (851 versus 1079;
. P
. <0.001) and were less likely to require intensive care (768 versus 879; 18% rate reduction,
. P
. =0.005), to receive intravenous positive inotropic agents (31% risk reduction,
. P
. <0.001), and to have implantation of a heart failure device or cardiac transplantation (22% risk reduction,
. P
. =0.07). The reduction in heart failure hospitalization with LCZ696 was evident within the first 30 days after randomization. Worsening of symptom scores in surviving patients was consistently more common in the enalapril group. LCZ696 led to an early and sustained reduction in biomarkers of myocardial wall stress and injury (N-terminal pro–B-type natriuretic peptide and troponin) versus enalapril.
.
.
.
. Conclusions—
. Angiotensin-neprilysin inhibition prevents the clinical progression of surviving patients with heart failure more effectively than angiotensin-converting enzyme inhibition.
.
.
. Clinical Trial Registration—
.
. URL:
. http://www.clinicaltrials.gov
. Unique identifier: NCT01035255.
.
.
Abstract.
Adingupu DD, Thorn CE, Casanova F, Elyas S, Gooding K, Gilchrist M, Aizawa K, Gates PE, Shore AC, Strain DW, et al (2015). Blood Oxygen Saturation After Ischemia is Altered with Abnormal Microvascular Reperfusion.
Microcirculation,
22(4), 294-305.
Abstract:
Blood Oxygen Saturation After Ischemia is Altered with Abnormal Microvascular Reperfusion.
OBJECTIVE: We have previously described a distinct abnormality in the cutaneous microcirculation that is characterized by an abnormal reperfusion response following an ischemic stimulus. We investigated the physiological significance of this abnormality; by measuring microvascular perfusion and blood oxygen saturation in groups stratified by three distinct reperfusion responses. METHODS: Cutaneous microvascular reperfusion after four minutes of arterial occlusion above the ankle was measured on the foot using laser Doppler fluximetry and optical reflectance spectroscopy in almost 400 adults. Individuals were stratified into three groups according to the microvascular reperfusion response: normal and two abnormal patterns (DEP and NDEP). RESULTS: Our main findings were that abnormal microvascular reperfusion responses (DEP and NDEP) had a higher baseline oxygen saturation (p = 0.005), a lower plateau in oxygen saturation (p < 0.0001 and
Abstract.
Author URL.
Elyas S, Adingupu D, Aizawa K, Shore AC, Strain WD, Gates PE (2015). Cerebral hemodynamics in patients with large vessel disease stroke and lacunar stroke.
INTERNATIONAL JOURNAL OF STROKE,
10, 368-368.
Author URL.
(2015). Efficacy of nitric oxide, with or without continuing antihypertensive treatment, for management of high blood pressure in acute stroke (ENOS): a partial-factorial randomised controlled trial. The Lancet, 385(9968), 617-628.
Goncalves I, Bengtsson E, Colhoun HM, Shore AC, Palombo C, Natali A, Edsfeldt A, Dunér P, Fredrikson GN, Björkbacka H, et al (2015). Elevated Plasma Levels of MMP-12 Are Associated with Atherosclerotic Burden and Symptomatic Cardiovascular Disease in Subjects with Type 2 Diabetes.
Arterioscler Thromb Vasc Biol,
35(7), 1723-1731.
Abstract:
Elevated Plasma Levels of MMP-12 Are Associated with Atherosclerotic Burden and Symptomatic Cardiovascular Disease in Subjects with Type 2 Diabetes.
OBJECTIVE: Matrix metalloproteinases (MMPs) degrade extracellular matrix proteins and play important roles in development and tissue repair. They have also been shown to have both protective and pathogenic effects in atherosclerosis, and experimental studies have suggested that MMP-12 contributes to plaque growth and destabilization. The objective of this study was to investigate the associations between circulating MMPs, atherosclerosis burden, and incidence of cardiovascular disease with a particular focus on type 2 diabetes mellitus. APPROACH AND RESULTS: Plasma levels of MMP-1, -3, -7, -10, and -12 were analyzed by the Proximity Extension Assay technology in 1500 subjects participating in the SUMMIT (surrogate markers for micro- and macrovascular hard end points for innovative diabetes tools) study, 384 incident coronary cases, and 409 matched controls in the Malmö Diet and Cancer study and in 205 carotid endarterectomy patients. Plasma MMP-7 and -12 were higher in subjects with type 2 diabetes mellitus, increased with age and impaired renal function, and was independently associated with prevalent cardiovascular disease, atherosclerotic burden (as assessed by carotid intima-media thickness and ankle-brachial pressure index), arterial stiffness, and plaque inflammation. Baseline MMP-7 and -12 levels were increased in Malmö Diet and Cancer subjects who had a coronary event during follow-up. CONCLUSIONS: the plasma level of MMP-7 and -12 are elevated in type 2 diabetes mellitus, associated with more severe atherosclerosis and an increased incidence of coronary events. These observations provide clinical support to previous experimental studies, demonstrating a role for these MMPs in plaque development, and suggest that they are potential biomarkers of atherosclerosis burden and cardiovascular disease risk.
Abstract.
Author URL.
Aizawa. K, Casanova F, Mawson D, Elyas S, Adingupu D, Gooding K, Strain D, Shore A, Gates P (2015). P3.5 TYPE 2 DIABETES EXACERBATES CAROTID ARTERY ECHOGENICITY AND CENTRAL ARTERY STIFFNESS IN MIDDLE-AGED AND OLDER INDIVIDUALS. Artery Research, 12(C), 11-11.
Palmer D, Strain WD, Webb B (2014). 242. Turning of the Tide: Does Tidemark Advancement Perpetuate Osteoarthritis. Rheumatology, 53(suppl_1), i150-i150.
McMurray JJV, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, et al (2014). Angiotensin–Neprilysin Inhibition versus Enalapril in Heart Failure. New England Journal of Medicine, 371(11), 993-1004.
Strain WD, Blüher M, Paldánius P (2014). Clinical inertia in individualising care for diabetes: is there time to do more in type 2 diabetes?.
Diabetes Ther,
5(2), 347-354.
Abstract:
Clinical inertia in individualising care for diabetes: is there time to do more in type 2 diabetes?
Clinical inertia is defined as the failure to establish appropriate targets and escalate treatment to achieve treatment goals. It accounts for a significant proportion of failure to achieve targets in the management of diabetes and contributes to up to 200,000 adverse diabetes- related outcomes per year. Despite a growing awareness of the phenomenon, and newer, better-tolerated agents for the control of diabetes, there has been little improvement over the last decade in the prevalence of clinical inertia. Although common-place in clinical practice, clinical inertia does not appear to affect clinical trials. There are lessons that may be translated from these randomised controlled trials to clinical practice, which that may improve the care for those with diabetes. Key amongst these interventions are good education, clear treatment strategy and more time for interaction between physician and patients, all of which appears to reduce clinical inertia as evidenced by the "placebo effect" of clinical trials. We plan to review here, the lessons that can be learnt from clinical trials and how these may translate to better care for people with diabetes.
Abstract.
Author URL.
McMurray JJV, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau J, Shi VC, Solomon SD, Swedberg K, et al (2014). Dual angiotensin receptor and neprilysin inhibition as an alternative to angiotensin‐converting enzyme inhibition in patients with chronic systolic heart failure: rationale for and design of the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM‐HF).
European Journal of Heart Failure,
15(9), 1062-1073.
Abstract:
Dual angiotensin receptor and neprilysin inhibition as an alternative to angiotensin‐converting enzyme inhibition in patients with chronic systolic heart failure: rationale for and design of the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM‐HF)
AimsAlthough the focus of therapeutic intervention has been on neurohormonal pathways thought to be harmful in heart failure (HF), such as the renin–angiotensin–aldosterone system (RAAS), potentially beneficial counter‐regulatory systems are also active in HF. These promote vasodilatation and natriuresis, inhibit abnormal growth, suppress the RAAS and sympathetic nervous system, and augment parasympathetic activity. The best understood of these mediators are the natriuretic peptides which are metabolized by the enzyme neprilysin. LCZ696 belongs to a new class of drugs, the angiotensin receptor neprilysin inhibitors (ARNIs), which both block the RAAS and augment natriuretic peptides.MethodsPatients with chronic HF, NYHA class II–IV symptoms, an elevated plasma BNP or NT‐proBNP level, and an LVEF of ≤40% were enrolled in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortailty and morbidity in Heart Failure trial (PARADIGM‐HF). Patients entered a single‐blind enalapril run‐in period (titrated to 10 mg b.i.d.), followed by an LCZ696 run‐in period (100 mg titrated to 200 mg b.i.d.). A total of 8436 patients tolerating both periods were randomized 1:1 to either enalapril 10 mg b.i.d. or LCZ696 200 mg b.i.d. The primary outcome is the composite of cardiovascular death or HF hospitalization, although the trial is powered to detect a 15% relative risk reduction in cardiovascular death.PerspectivesPARADIGM‐HF will determine the place of the ARNI LCZ696 as an alternative to enalapril in patients with systolic HF. PARADIGM‐HF may change our approach to neurohormonal modulation in HF.Trial registrationNCT01035255
Abstract.
McCluskey L, Jagger O, Strain WD (2014). Hypoglycemia associated with impaired mobility and diminished confidence in an elderly person with type 2 diabetes.
Diabetic Hypoglycemia,
7(1), 11-14.
Abstract:
Hypoglycemia associated with impaired mobility and diminished confidence in an elderly person with type 2 diabetes
An elderly lady with type 2 diabetes presented with the complaint of lack of confidence when mobilizing. Although she had experienced a single fall, this had resulted in a disproportionate reduction in her confidence and she described intermittent "dizzy episodes" when walking. The latter were abolished after discontinuation of her sulfonylurea therapy, but rehabilitation to independent life required a period of 7 weeks in hospital. This case highlights indirect consequences of hypoglycemia in older patients, with reduced quality of life and the healthcare cost of an avoidable hospital admission. In such cases, the need for hypoglycemic therapy should be reviewed, in view of the patient's limited life expectancy and the therapeutic delay between good glycemic control and clinical outcomes. Hypoglycemia in older adults is associated with an increased risk of falls causing injury with fractures, and cerebrovascular events such as stroke. In some, recurrent hypoglycemia may accelerate cognitive decline. The effect of hypoglycemia on quality of life is more difficult to measure. The choice of glucose-lowering agent in the frail elderly person should consider the potential risk of hypoglycemia, rather than achieving glycemic targets.
Abstract.
Jones LC, Sword J, Strain WD, Ostrowski C (2014). P083: the correlation between patients, patient's relatives and healthcare professionals interpretation of quality of life – a prospective study. European Geriatric Medicine, 5, S108-S108.
Aizawa K, Elyas S, Adingpu D, Shore A, Strain D, Gates P (2014). P3.10 REACTIVITY TO LOW-FLOW IN THE BRACHIAL ARTERY: a POTENTIAL DETERMINANT FOR FLOW-MEDIATED DILATORY RESPONSE. Artery Research, 8(4), 138-138.
Strain WD, Cos X, Hirst M, Vencio S, Mohan V, Vokó Z, Yabe D, Blüher M, Paldánius PM (2014). Time to do more: addressing clinical inertia in the management of type 2 diabetes mellitus.
Diabetes Res Clin Pract,
105(3), 302-312.
Abstract:
Time to do more: addressing clinical inertia in the management of type 2 diabetes mellitus.
AIMS: Clinical inertia, the tendency to maintain current treatment strategies despite results demanding escalation, is thought to substantially contribute to the disconnect between clinical aspirations for patients with diabetes and targets achieved. We wished to explore potential causes of clinical inertia among physicians and people with diabetes. METHODS: a 20-min online survey of 652 adults with diabetes and 337 treating physicians in six countries explored opinions relating to clinical inertia from both perspectives, in order to correlate perceptions and expectations relating to diagnosis, treatment, diabetes complications and therapeutic escalation. RESULTS: Physicians had low expectations for their patients, despite the belief that the importance of good glycaemic control through lifestyle and pharmacological interventions had been adequately conveyed. Conversely, people with diabetes had, at best, a rudimentary understanding of the risks of complications and the importance of good control; indeed, only a small proportion believed lifestyle changes were important and the majority did not intend to comply. CONCLUSIONS: the principal findings of this survey suggest that impairments in communication are at the heart of clinical inertia. This manuscript lays out four key principles that we believe are achievable in all environments and can improve the lives of people with diabetes.
Abstract.
Author URL.
Gurung A, Mazzaro L, Gates PE, Strain D, Shore AC, Shandas R (2013). Abstract 246: Echo Particle Image Velocimetry Generates Wall Shear Stress Biomarkers with Higher Accuracy than Doppler: Clinical Studies on 24 Healthy and 12 Tia Subjects. Arteriosclerosis Thrombosis and Vascular Biology, 33(suppl_1).
Strain WD, Hughes AD, Mayet J, Wright AR, Kooner J, Chaturvedi N, Shore AC (2013). Attenuated systemic microvascular function in men with coronary artery disease is associated with angina but not explained by atherosclerosis.
Microcirculation,
20(7), 670-677.
Abstract:
Attenuated systemic microvascular function in men with coronary artery disease is associated with angina but not explained by atherosclerosis.
INTRODUCTION: Refractory angina is the occurrence of clinical symptoms despite maximal therapy. We investigated associations between microvascular function, atherosclerotic burden, and clinical symptoms in subjects with CAD. METHODS: Skin microvascular response to heating and ischemia was assessed in 167 male volunteers by laser Doppler fluximetry; 82 with CAD on maximal therapy and 85 with no known CAD (noCAD). CAC scores, carotid IMT, and femoral IMT were measured and symptoms were scored using the Rose angina questionnaire. RESULTS: Patients with CAD had poorer microvascular response to heating (114[95% CI 106-122]au CAD vs. 143[134-153]au no CAD; p < 0.0001) and ischemia (42[38-46]au CAD vs. 53[78-58]au. noCAD; p = 0.001). Thirty-eight percent of the noCAD group had elevated CAC scores. There were no associations between markers of atherosclerosis and microvascular function. Forty-two percent of the CAD group had refractory angina. This was associated with impaired microvascular function compared to those with elevated CAC scores but no symptoms (109 [95-124]au vs. 131[122-140]au; p = 0.008). CONCLUSIONS: Men with symptomatic CAD have poorer microvascular function compared to individuals without CAD. Microvascular function does not correlate with atherosclerosis, but is impaired in individuals with refractory angina. Microvascular dysfunction may play a role in the symptomatology of angina.
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Author URL.
Gosling O, Morgan-Hughes G, Iyengar S, Strain W, Loader R, Shore A, Roobottom C (2013). Computed tomography to diagnose coronary artery disease: a reduction in radiation dose increases applicability.
Clinical Radiology,
68(4), 340-345.
Abstract:
Computed tomography to diagnose coronary artery disease: a reduction in radiation dose increases applicability
Aim: to assess the effects of dose-saving algorithms on the radiation dose in an established computed tomography coronary angiography (CTCA) clinical service. Materials and methods: a 3 year retrospective analysis of all patients attending for a clinically indicated CTCA was performed. The effective dose was calculated using a cardiac-specific conversion factor [0.028 mSv(mGy·cm)-1]. Patients were stratified by the advent of new scanning technology and dose-saving protocols. Results: Between September 2007 and August 2010, 1736 examinations were performed. In the first 6 months, 150 examinations were performed with a mean effective dose of 29.6 mSv (99% CI 26.6-33 mSv). In March 2008 prospective electrocardiogram (ECG) gating was installed; reducing the effective dose to 13.6 mSv (99% CI 12.5-14.9 mSv). In March 2009, the scanner parameters were set to a minimal exposure time and 100 kV in patients with a body mass index (BMI) of
Abstract.
Gosling O, Morgan-Hughes G, Iyengar S, Strain W, Loader R, Shore A, Roobottom C (2013). Computed tomography to diagnose coronary artery disease: a reduction in radiation dose increases applicability.
Clin Radiol,
68(4), 340-345.
Abstract:
Computed tomography to diagnose coronary artery disease: a reduction in radiation dose increases applicability.
AIM: to assess the effects of dose-saving algorithms on the radiation dose in an established computed tomography coronary angiography (CTCA) clinical service. MATERIALS AND METHODS: a 3 year retrospective analysis of all patients attending for a clinically indicated CTCA was performed. The effective dose was calculated using a cardiac-specific conversion factor [0.028 mSv(mGy·cm)(-1)]. Patients were stratified by the advent of new scanning technology and dose-saving protocols. RESULTS: Between September 2007 and August 2010, 1736 examinations were performed. In the first 6 months, 150 examinations were performed with a mean effective dose of 29.6 mSv (99% CI 26.6-33 mSv). In March 2008 prospective electrocardiogram (ECG) gating was installed; reducing the effective dose to 13.6 mSv (99% CI 12.5-14.9 mSv). In March 2009, the scanner parameters were set to a minimal exposure time and 100 kV in patients with a body mass index (BMI) of
Abstract.
Author URL.
Hope SV, Strain WD (2013). Hypoglycemia in the elderly.
Diabetic Hypoglycemia,
6(1), 3-10.
Abstract:
Hypoglycemia in the elderly
Hypoglycemia is a common, under-recognized complication of the management of type 2 diabetes. Elderly individuals have a higher burden of co-morbidities, cognitive impairment, physical dysfunction and frailty, which makes them more vulnerable to complications of hypoglycemia, such as falls, fractures, cognitive impairment and cardiovascular events, than younger patients. Furthermore, with ageing comes impairment of autoregulatory responses, which means the symptoms of hypoglycemia are often less specific, and are therefore either missed or incorrectly diagnosed as transient ischemic attacks or other cerebrovascular events. Older adults with diabetes have a greater risk of hypoglycemia associated with the physiological decline of ageing, and the extended duration of diabetes and insulin treatment. The elderly are also more prone to the effects of hypoglycemia such as the increased risk of accidents, falls and fractures, hospitalizations, in-hospital mortality, and long-term impairment of cognition. Using individualized treatment targets to base treatment strategies around individual circumstances may reduce the risk of hypoglycemia.
Abstract.
Strain WD, Lukashevich V, Kothny W, Hoellinger MJ, Paldánius PM (2013). Individualised treatment targets for elderly patients with type 2 diabetes using vildagliptin add-on or lone therapy (INTERVAL): a 24 week, randomised, double-blind, placebo-controlled study.
The Lancet,
382(9890), 409-416.
Abstract:
Individualised treatment targets for elderly patients with type 2 diabetes using vildagliptin add-on or lone therapy (INTERVAL): a 24 week, randomised, double-blind, placebo-controlled study
Background Guidelines suggest setting individualised targets for glycaemic control in elderly patients with type 2 diabetes, despite no evidence. We aimed to assess the feasibility of setting and achieving individualised targets over 24 weeks along with conventional HbA1c reduction using vildagliptin versus placebo. Methods in this multinational, double-blind, 24 week study, we enrolled drug-naive or inadequately controlled (glycosylated haemoglobin a 1c [HbA1c] ≥7·0% to ≤10·0%) patients with type 2 diabetes aged 70 years or older from 45 outpatient centres in Europe. Investigators set individualised treatment targets on the basis of age, baseline HbA1c, comorbidities, and frailty status before a validated automated system randomly assigned patients (1:1) to vildagliptin (50 mg once or twice daily as per label) or placebo. Coprimary efficacy endpoints were proportion of patients reaching their investigator-defined HbA1c target and HbA1c reduction from baseline to study end. The study is registered with ClinicalTrials.gov, number NCT01257451, and European Union Drug Regulating Authorities Clinical Trials database, number 2010-022658-18. Findings Between Dec 22, 2010, and March 14, 2012, we randomly assigned 139 patients each to the vildagliptin and placebo groups. 37 (27%) of 137 patients in the placebo group achieved their individualised targets by education and interactions with the study team alone and 72 (52·6%) of 137 patients achieved their target in the vildagliptin group (adjusted odds ratio 3·16, 96·2% CI 1·81-5·52; p
Abstract.
Strain WD, Lukashevich V, Kothny W, Hoellinger M-J, Paldánius PM (2013). Individualised treatment targets for elderly patients with type 2 diabetes using vildagliptin add-on or lone therapy (INTERVAL): a 24 week, randomised, double-blind, placebo-controlled study.
Lancet,
382(9890), 409-416.
Abstract:
Individualised treatment targets for elderly patients with type 2 diabetes using vildagliptin add-on or lone therapy (INTERVAL): a 24 week, randomised, double-blind, placebo-controlled study.
BACKGROUND: Guidelines suggest setting individualised targets for glycaemic control in elderly patients with type 2 diabetes, despite no evidence. We aimed to assess the feasibility of setting and achieving individualised targets over 24 weeks along with conventional HbA1c reduction using vildagliptin versus placebo. METHODS: in this multinational, double-blind, 24 week study, we enrolled drug-naive or inadequately controlled (glycosylated haemoglobin A1c [HbA1c] ≥7·0% to ≤10·0%) patients with type 2 diabetes aged 70 years or older from 45 outpatient centres in Europe. Investigators set individualised treatment targets on the basis of age, baseline HbA1c, comorbidities, and frailty status before a validated automated system randomly assigned patients (1:1) to vildagliptin (50 mg once or twice daily as per label) or placebo. Coprimary efficacy endpoints were proportion of patients reaching their investigator-defined HbA1c target and HbA1c reduction from baseline to study end. The study is registered with ClinicalTrials.gov, number NCT01257451, and European Union Drug Regulating Authorities Clinical Trials database, number 2010-022658-18. FINDINGS: Between Dec 22, 2010, and March 14, 2012, we randomly assigned 139 patients each to the vildagliptin and placebo groups. 37 (27%) of 137 patients in the placebo group achieved their individualised targets by education and interactions with the study team alone and 72 (52·6%) of 137 patients achieved their target in the vildagliptin group (adjusted odds ratio 3·16, 96·2% CI 1·81-5·52; p
Abstract.
Author URL.
Adingupu DD, Elyas S, Casanova F, Gates PE, Shore AC, Strain WD (2013). Microvascular autoregulatory response to ischaemia and pulse pressure.
JOURNAL OF HUMAN HYPERTENSION,
27(10), 652-653.
Author URL.
Adingupu DD, Thorn C, Casanova F, Elyas S, Gates PE, Strain WD, Shore AC (2013). Microvascular autoregulatory response to ischaemia in the skin and association with mean blood oxygen saturation.
JOURNAL OF HUMAN HYPERTENSION,
27(10), 640-641.
Author URL.
Aizawa K, Elyas S, Adingupu DD, Shore AC, Strain WD, Gates PE (2013). P2.17 ECHOGENICITY OF THE COMMON CAROTID ARTERY INTIMA-MEDIA COMPLEX IN STROKE. Artery Research, 7(3-4), 123-123.
Elyas S, Adingupu D, Thorn C, Gates PE, Shore AC, Strain WD (2013). Skin microvascular function is impaired in patients with small vessel disease stroke but not in patients with large vessel disease stroke when compared to healthy controls.
CEREBROVASCULAR DISEASES,
35, 521-521.
Author URL.
Adingupu DD, Elyas S, Thorn CE, Gates PE, Shore AC, Strain WD (2013). The prevalence of abnormal microvascular response (peaks) in stroke or transient ischaemic attack (TIA) patients compared with Controls and association with impaired sympathetic activity.
CEREBROVASCULAR DISEASES,
35, 547-547.
Author URL.
Aizawa K, Elyas S, Adingupu DD, Shore AC, Strain WD, Gates PE (2012). Brachial Artery Low Flow-Mediated Constriction in Individuals with Increased Cardiovascular Risk.
MEDICINE AND SCIENCE IN SPORTS AND EXERCISE,
44, 585-585.
Author URL.
Foster J, Baillie PA, Strain WD (2012). Hypoglycemia precipitating prolonged QT interval and myocardial ischemia in a patient with coronary heart disease and renal failure.
Diabetic Hypoglycemia,
4(3), 9-11.
Abstract:
Hypoglycemia precipitating prolonged QT interval and myocardial ischemia in a patient with coronary heart disease and renal failure
A 75-year-old lady with end-stage renal nephropathy attributed to type 2 diabetes and ischemic heart disease was admitted as a medical emergency with right lower lobe pneumonia. In addition to antibiotic therapy, her dose of isophane insulin was increased by 20%. The following morning she became acutely unwell with prominent autonomic symptoms and chest tightness. Her ECG demonstrated anterolateral ischemia with a prolonged QT interval and her blood glucose was 2.7 mmol/l (48.6 mg/dl). She was treated with intravenous and oral dextrose and her symptoms resolved. Her ECG demonstrated resolution of the anterolateral changes; however the prolonged QT interval persisted for 48 hours. This was associated with a rise and fall in her serum Troponin T measurement, peaking at 83 ng/l (normal range 0-14 ng/l). Her insulin dose was restored to the previous amount and her recovery was uncomplicated. This case highlights the increased risk of hypoglycemia in patients with end-stage renal disease who have impaired renal clearance of insulin, and the subsequent risk of hypoglycemia provoking myocardial ischemia.
Abstract.
Park C, Bathula R, Shore AC, Tillin T, Strain WD, Chaturvedi N, Hughes AD (2012). Impaired post-ischaemic microvascular hyperaemia in Indian Asians is unexplained by diabetes or other cardiovascular risk factors.
Atherosclerosis,
221(2), 503-507.
Abstract:
Impaired post-ischaemic microvascular hyperaemia in Indian Asians is unexplained by diabetes or other cardiovascular risk factors
Objective: People of Indian Asian descent have an increased risk of cardiovascular disease (CVD) that cannot be explained by diabetes and other established CVD risk factors. We investigated if microcirculatory function was impaired in a population-based sample of people of Indian Asian descent compared with Europeans in the UK and whether any differences could be accounted for by diabetes or other CVD risk factors. Research design and methods: Cutaneous microvascular function was assessed using laser Doppler fluximetry in response to heating to 42. °C (maximum hyperaemia) and 3. min arterial occlusion (post occlusive reactive hyperaemia: PORH) in 148 Indian Asians and 147 Europeans. Blood pressure, anthropometry and fasting bloods were also measured. Results: Maximum hyperaemia and minimum resistance did not differ significantly by ethnicity. Resting flux and PORH were lower in Indian Asians and time to peak of PORH was prolonged. Diabetes was associated with reduced maximum hyperaemia and PORH. Adjustment for diabetes accounted for differences in resting flux and time to peak but not differences in PORH (Europeans. =. 45.0 (40.3, 50.1)au, Indian Asians. =. 35.6 (31.9, 39.7)au, mean (95% confidence interval); p=. 0.008 after adjustment). Differences in conventional CVD risk factors did not account for interethnic differences in microvascular responses. Conclusions: People of Indian Asian descent have impaired post-occlusive reactive hyperaemia unexplained by diabetes, dysglycaemia or other CVD risk factors. Abnormal microvascular function in response to ischaemia could represent a novel mechanism contributing to the elevated risk of CVD in Indian Asians. © 2011 Elsevier Ireland Ltd.
Abstract.
Park C, Bathula R, Shore AC, Tillin T, Strain WD, Chaturvedi N, Hughes AD (2012). Impaired post-ischaemic microvascular hyperaemia in Indian Asians is unexplained by diabetes or other cardiovascular risk factors.
Atherosclerosis,
221(2), 503-507.
Abstract:
Impaired post-ischaemic microvascular hyperaemia in Indian Asians is unexplained by diabetes or other cardiovascular risk factors.
OBJECTIVE: People of Indian Asian descent have an increased risk of cardiovascular disease (CVD) that cannot be explained by diabetes and other established CVD risk factors. We investigated if microcirculatory function was impaired in a population-based sample of people of Indian Asian descent compared with Europeans in the UK and whether any differences could be accounted for by diabetes or other CVD risk factors. RESEARCH DESIGN AND METHODS: Cutaneous microvascular function was assessed using laser Doppler fluximetry in response to heating to 42 °C (maximum hyperaemia) and 3 min arterial occlusion (post occlusive reactive hyperaemia: PORH) in 148 Indian Asians and 147 Europeans. Blood pressure, anthropometry and fasting bloods were also measured. RESULTS: Maximum hyperaemia and minimum resistance did not differ significantly by ethnicity. Resting flux and PORH were lower in Indian Asians and time to peak of PORH was prolonged. Diabetes was associated with reduced maximum hyperaemia and PORH. Adjustment for diabetes accounted for differences in resting flux and time to peak but not differences in PORH (Europeans = 45.0 (40.3, 50.1)au, Indian Asians = 35.6 (31.9, 39.7)au, mean (95% confidence interval); p = 0.008 after adjustment). Differences in conventional CVD risk factors did not account for interethnic differences in microvascular responses. CONCLUSIONS: People of Indian Asian descent have impaired post-occlusive reactive hyperaemia unexplained by diabetes, dysglycaemia or other CVD risk factors. Abnormal microvascular function in response to ischaemia could represent a novel mechanism contributing to the elevated risk of CVD in Indian Asians.
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Author URL.
Strain WD, Adingupu DD, Shore AC (2012). Microcirculation on a large scale: techniques, tactics and relevance of studying the microcirculation in larger population samples.
Microcirculation,
19(1), 37-46.
Abstract:
Microcirculation on a large scale: techniques, tactics and relevance of studying the microcirculation in larger population samples.
The role of microcirculatory dysfunction is increasingly being recognized in the etiopathogenesis of cardiovascular disease. Whilst the importance of detailed mechanistic studies to determine the exact nature of these disturbances is without question, it was large-scale population-based studies that first identified the associations between deranged microvascular perfusion, autoregulation or structure, and subsequent target organ damage. This is the subject of considerable studies to establish whether there is a causal effect in either direction, or simply represents shared risk factors, although it is most likely to be a complex combination of bidirectional interactions. The techniques for investigating microcirculatory function have evolved almost exponentially over the last 75 years: So too have the strategies for investigation. Current epidemiological studies are focusing on attempting to untangle the inter-relationship between risk factors and pathological mechanisms to attempt to determine whether these represent therapeutic targets or simple markers of unmeasured risk. We plan to review the techniques used for these population-based studies, the advances made, and the clinical implications derived.
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Author URL.
Aizawa K, Elyas S, Adingupu DD, Shore AC, Strain WD, Gates PE (2012). P4.17 INFLUENCE OF ESTIMATED WALL SHEAR RATE INDICES ON CAROTID ARTERY INTIMA-MEDIA THICKNESS AND INTIMA-MEDIA COMPLEX ECHOGENICITY. Artery Research, 6(4), 188-188.
Elyas S, Majekolagbe D, D'Abate F, Aizawa K, Gates PE, Shore AC, Strain WD (2012). PREVALENCE OF SKIN MICROVASCULAR AUTOREGULATORY DYSFUNCTION IN PATIENTS WHO SUFFER STROKE OR TIA COMPARED TO THE GENERAL POPULATION.
AGE AND AGEING,
41, 81-81.
Author URL.
Thompson D, Thornes J, Woods J, Khan A, Kreppel S, Palmer D, Phillips S, Shamsuddin N, Solman J, Strain WD, et al (2012). SODIUM DYSREGULATION AND ITS ASSOCIATION WITH MORTALITY.
AGE AND AGEING,
41, 37-37.
Author URL.
Shamsuddin N, Solman J, Khan A, Kreppel S, Palmer D, Phillips S, Thompson D, Thornes J, Woods J, Strain WD, et al (2012). THE RELATIONSHIP BETWEEN HYPONATRAEMIA AND LENGTH OF STAY IN ELDERLY CARE PATIENTS.
AGE AND AGEING,
41, 42-42.
Author URL.
(2012). The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): a randomised controlled trial. The Lancet, 379(9834), 2352-2363.
Aizawa K, Gates PE, Strain WD, Gosling OE, Mazzaro L, Zhang F, Barker AJ, Fulford J, Shore AC, Bellenger NG, et al (2011). Arterial Wall Shear Stress Measurement in Vivo Using Echo Particle Image Velocimetry (Echo PIV).
MEDICINE AND SCIENCE IN SPORTS AND EXERCISE,
43(5), 743-744.
Author URL.
Zhang F, Lanning C, Mazzaro L, Barker AJ, Gates PE, Strain WD, Fulford J, Gosling OE, Shore AC, Bellenger NG, et al (2011). In vitro and preliminary in vivo validation of echo particle image velocimetry in carotid vascular imaging.
Ultrasound Med Biol,
37(3), 450-464.
Abstract:
In vitro and preliminary in vivo validation of echo particle image velocimetry in carotid vascular imaging.
Noninvasive, easy-to-use and accurate measurements of wall shear stress (WSS) in human blood vessels have always been challenging in clinical applications. Echo particle image velocimetry (Echo PIV) has shown promise for clinical measurements of local hemodynamics and wall shear rate. Thus far, however, the method has only been validated under simple flow conditions. In this study, we validated Echo PIV under in vitro and in vivo conditions. For in vitro validation, we used an anatomically correct, compliant carotid bifurcation flow phantom with pulsatile flow conditions, using optical particle image velocimetry (optical PIV) as the reference standard. For in vivo validation, we compared Echo PIV-derived 2-D velocity fields obtained at the carotid bifurcation in five normal subjects against phase-contrast magnetic resonance imaging (PC-MRI)-derived velocity measurements obtained at the same locations. For both studies, time-dependent, 2-D, two-component velocity vectors; peak/centerline velocity, flow rate and wall shear rate (WSR) waveforms at the common carotid artery (CCA), carotid bifurcation and distal internal carotid artery (ICA) were examined. Linear regression, correlation analysis and Bland-Altman analysis were used to quantify the agreement of different waveforms measured by the two techniques. In vitro results showed that Echo PIV produced good images of time-dependent velocity vector maps over the cardiac cycle with excellent temporal (up to 0.7 ms) and spatial (∼0.5 mm) resolutions and quality, comparable with optical PIV results. Further, good agreement was found between Echo PIV and optical PIV results for velocity and WSR measurements. In vivo results also showed good agreement between Echo PIV velocities and phase contrast MRI velocities. We conclude that Echo PIV provides accurate velocity vector and WSR measurements in the carotid bifurcation and has significant potential as a clinical tool for cardiovascular hemodynamics evaluation.
Abstract.
Author URL.
Aizawa K, Elyas S, D’Abate F, Majekolagbe D, Shore AC, Strain WD, Gates PE (2011). P8.08 THE RELATIONSHIP BETWEEN BRACHIAL ARTERY FLOW-MEDIATED DILATION AND SHEAR RATE IN INDIVIDUALS WITH INCREASED CARDIOVASCULAR RISK. Artery Research, 5(4), 184-184.
Strain WD, Elyas S, Gates PE, Shore AC (2010). Age-related change in endothelial and microvessel function and therapeutic consequences.
Reviews in Clinical Gerontology,
20(3), 161-170.
Abstract:
Age-related change in endothelial and microvessel function and therapeutic consequences
As the absolute numbers and proportion of older adults increases across most of the developed world, a greater understanding of the aetiopathogenic mechanisms of the increased vascular risk and their therapeutic implications becomes essential to all clinicians assessing and managing the geriatric patient. The role of endothelial function and the microcirculation is increasingly recognized in the maintenance of adequate perfusion, and their dysfunction is thought to be an early and potentially reversible mechanism by which age acts to increase cardiovascular risk. Here we review evidence that altered microvascular function appears before other recognized predictors of vascular disease, and progresses from childhood to late adult life, preceding fulminant atherosclerotic or arteriosclerotic disease. Low birth-weight babies have reduced endothelial function in skin microvessels at 3 months, and by age ten brachial artery endothelial function is reduced in comparison with normal birth-weight babies. In overweight/obese adolescent children with clustering of traditional cardiovascular disease risk factors, endothelial function is lower compared with normal weight children and this appears to persist into early adulthood. Adult ageing is associated with impaired microvessel endothelial function and an increase in capillary blood pressure, independent of brachial artery blood pressure. Biological and lifestyle factors that influence microvessel function include body fat and visceral adiposity, sex hormone status, diet and physical activity. Exploration of the therapeutic implications for management of endothelial dysfunction remains in embryonic state. The use of ACE-inhibitors, angiotensin receptor blockers and direct renin inhibitors in patients with evidence of microvascular damage such as retinopathy and microalbuminuria has been established; however, in the general older population the benefit has yet to be established. Therefore current recommendations are to screen for microvascular damage and if present target treatments after control of other vascular risk factors such as hypertension. Copyright © 2010 Cambridge University Press.
Abstract.
Strain WD, Shore AC, Melzer D (2010). Albumin:creatinine ratio predicts mortality after stroke: analysis of the Third National Health and Nutrition Examination Survey.
J Am Geriatr Soc,
58(12), 2434-2435.
Author URL.
Strain WD, Chaturvedi N, Hughes A, Nihoyannopoulos P, Bulpitt CJ, Rajkumar C, Shore AC (2010). Associations between cardiac target organ damage and microvascular dysfunction: the role of blood pressure.
J Hypertens,
28(5), 952-958.
Abstract:
Associations between cardiac target organ damage and microvascular dysfunction: the role of blood pressure.
BACKGROUND: Microvascular dysfunction may be an early precursor of cardiovascular disease (CVD). Increased left ventricular mass (LVM), concentric left ventricular remodelling and increased left atrial size are the factors that could predict future CVD. We investigated whether microvascular dysfunction was associated with these cardiac measures. METHODS AND RESULTS: Laser Doppler fluximetry of skin vessels was used to study associations with risk factors and echocardiographic measurements of LVM, relative wall thickness (RWT), and left atrial size in 305 people (aged 40-65 years; 117 with type 2 diabetes). Flow in response to a 3-min arterial occlusion was measured. Postischaemic peak flow responses were categorized into three distinct groups: slow rise to peak (normal), nondominant early peak group (mildly abnormal) and a dominant early peak (abnormal). Those with a dominant early peak had higher blood pressure (P = 0.001), weight (P = 0.001), fasting glucose (P = 0.001) and prevalence of diabetes (P = 0.02). LVM (P = 0.01), RWT (P < 0.001) and left atrial size (P < 0.001) were greater with worsening postischaemic peak flow responses. Differences in LVM between postischaemic response groups were accounted for by blood pressure (BP). However, differences in BP and other CVD risk factors did not account for the greater RWT and left atrial size observed in the more adverse peak response groups [geometric mean of RWT [95% confidence interval (CI)] 0.40 (0.38-0.41) vs. 0.41 (0.40-0.42) vs. 0.43 (0.41-0.45), P = 0.007; left atrial size 36.1 (35.4-36.1) vs. 37.4 (36.8-38.0) vs. 38.7 (37.5-40.0), P = 0.002 for normal vs. mildly abnormal vs. abnormal respectively]. CONCLUSION: an abnormal microcirculatory cutaneous peak flow response following ischaemia is associated with adverse cardiac remodelling, independent of CVD risk factors including blood pressure.
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Strain WD, Hughes AD, Mayet J, Wright AR, Kooner J, Chaturvedi N, Shore AC (2010). Attenuation of microvascular function in those with cardiovascular disease is similar in patients of Indian Asian and European descent.
BMC Cardiovasc Disord,
10Abstract:
Attenuation of microvascular function in those with cardiovascular disease is similar in patients of Indian Asian and European descent.
BACKGROUND: Indian Asians are at increased risk of cardiovascular death which does not appear to be explained by conventional risk factors. As microvascular disease is also more prevalent in Indian Asians, and as it is thought to play a role in the development of macrovascular disease, we decided to determine whether impaired microcirculation could contribute to this increased cardiovascular risk in Indian Asians. METHODS: Forearm skin laser Doppler fluximetry in response to heating and ischaemia was assessed in 83 Europeans (41 with angiographically confirmed atherosclerotic coronary artery disease (CAD) and 42 from the general population) and 84 Indian Asians (41 with CAD). Explanations for differences in microvascular function were sought using multivariate analysis including conventional cardiovascular risk factors. RESULTS: Compared to ethnically matched control populations both Europeans and Indian Asians with CAD had poorer microvascular responses to heating than those without (117(95% CI 105-131) vs. 142(130-162) arbitrary units, (au) for Europeans and 111(101-122) vs. 141(131-153)au for Indian Asians) and to ischaemia (44(38-50) vs. 57(49-67)au & 39(34-45) vs. 49(43-56)au respectively). These differences were not accounted for by conventional cardiovascular risk factors. There was no ethnic difference in the attenuation of microvascular function associated with CAD. CONCLUSION: Patients of European and Indian Asian descent with symptomatic CAD have poorer microvascular maximal tissue perfusion and reactive hyperaemia in the skin compared to ethnically matched asymptomatic control populations. Despite the increased cardiovascular risk in Indian Asians, the attenuation of microvascular function associated with CAD was equivalent in the ethic groups. This suggests that in Indian Asians microcirculation does not explain the increased susceptibility to CAD.
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Mahal S, Strain WD, Martinez-Perez ME, Thom SAM, Chaturvedi N, Hughes AD (2009). Comparison of the retinal microvasculature in European and African-Caribbean people with diabetes.
Clin Sci (Lond),
117(6), 229-236.
Abstract:
Comparison of the retinal microvasculature in European and African-Caribbean people with diabetes.
Diabetes aggravates the impact of elevated BP (blood pressure) on the microcirculation, and people of African ancestry with diabetes are more susceptible to microvascular damage than Europeans. In the present study, we investigated possible differences in the retinal microcirculation in people of European and African-Caribbean ethnicity with diabetes that might account for this. A total of 51 subjects with Type 2 diabetes (age 40-65 years; 25 male; 29 African-Caribbean) were studied. Clinic and 24 h ambulatory BP, and fasting glucose, insulin and lipids were measured. Digital retinal images were analysed using custom-written semi-automatic software to determine: LDR (length/diameter ratio) and AVR (arteriolar/venular diameter ratio), branching angles, vessel tortuosity and NT (number of terminal vessel branches). Arterioles were narrower in European people with diabetes than in African-Caribbean people with diabetes [mean (S.D.) arteriolar diameter, 76 (7) compared with 82 (11) microm respectively (P=0.03); arteriolar LDR, 28.1 (8.5) compared with 23.7 (7.0) respectively (P=0.046); and AVR, 0.66 (0.21) compared with 0.90 (0.36) respectively (P=0.028)]. Ethnic differences in arteriolar LDR, arteriolar diameter and AVR were not explained by differences in BP, but were attenuated by adjustment for the duration of diabetes. There was no significant relationship between BP and arteriolar narrowing in the group as a whole, although the relationship between arteriolar LDR and systolic BP was stronger in Europeans than African-Caribbeans [beta=0.08 (0.07) compared with beta=0.03 (0.06); P=0.03]. In conclusion, in the presence of diabetes, a relationship between BP and retinal arteriolar diameter was not evident and implies impaired small artery remodelling in the presence of diabetes. African-Caribbean people with diabetes have wider retinal arterioles and this could contribute to enhanced microvascular damage in this ethnic group.
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Gates PE, Strain WD, Shore AC (2009). Human endothelial function and microvascular ageing.
Exp Physiol,
94(3), 311-316.
Abstract:
Human endothelial function and microvascular ageing.
Age is a primary risk factor for cardiovascular disease, and this is an increasingly important public health concern because of an increase in the absolute number and proportion of the population at an older age in many countries. A key component of cardiovascular ageing is reduced function of the vascular endothelium, and this probably contributes to the impaired microvessel function observed with ageing in multiple vascular beds. In turn, impaired microvessel function is thought to contribute to the pathophysiology of cardiovascular and metabolic diseases. Here we review evidence that the first signs of altered endothelial and microvessel function can appear in childhood and at all stages of the human lifespan; low-birth-weight babies have reduced endothelial function in skin microvessels at 3 months, and by age 10 years their brachial artery endothelial function is reduced in comparison with normal-birth-weight babies. In overweight/obese adolescent children with clustering of traditional cardiovascular disease risk factors, endothelial function is reduced compared with normal-weight children, and this appears to persist into early adulthood. Adult ageing is associated with impaired microvessel endothelial function and an increase in capillary blood pressure. Biological and lifestyle factors that influence microvessel function include body fat and visceral adiposity, sex hormone status, diet and physical activity. The mechanisms underlying age-associated changes in microvessel function are uncertain but may involve alterations in nitric oxide, prostanoid, endothelium-derived hyperpolarizing factor(s) and endothelin-1 pathways.
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Zhang F, Barker AJ, Gates PE, Strain WD, Fulford J, Mazzaro L, Shore AC, Bellenger NG, Lanning C, Shandas R, et al (2009). Noninvasive wall shear stress measurements in human carotid artery using echo particle image velocimetry: Initial clinical studies.
Proceedings - IEEE Ultrasonics Symposium, 562-565.
Abstract:
Noninvasive wall shear stress measurements in human carotid artery using echo particle image velocimetry: Initial clinical studies
Wall shear stress (WSS) has been shown to be important to endothelial cell function and gene expression. Previous studies have shown that fluid dynamics might be closely related to the initialization of atherosclerotic plaques which preferentially originate in areas of disturbed flow in human vessels, where WSS is low or oscillatory. We recently developed a novel ultrasound-based technique, termed echo particle image velocimetry (echo PIV), by which the multi-component hemodynamic information in human cardiovascular system could be assessed. In this paper, we show that echo PIV was successfully employed to measure hemodynamic information in the right common carotid artery (rCCA) of ten healthy volunteers and that the values show good agreement with phase-contrast magnetic resonance imaging (PC-MRI) measurements with mean absolute differences (mean±SD) of 10.0%±9.8%, 10.1%±8.8% and 17.0%±15.3% for velocity, flow rate and WSS, respectively. In particular, the mean WSS (dynes/cm∧2) in rCCA of ten volunteers was found to be 9.2±2.0 by echo PIV, and 8.0±1.4 by PC-MRI, both in agreement with published data. We further showed that calculating WSS by either peak/mean velocity or flow rate together with arterial diameter was invalid for in-vivo measurements due to invalidity of assuming parabolic velocity profile in carotid artery. We found that the peak velocity across radial direction in rCCA was about 1.6 times of the mean velocity, not 2 times as it should be in parabolic distribution. In conclusion, echo PIV demonstrated several advantages over traditional techniques in terms of both temporal and spatial resolution when measuring WSS in human vessels. ©2009 IEEE.
Abstract.
Todd DM, Strain WD (2007). Ethnic differences in infants and maternal outcomes in gestational diabetes.
DIABETIC MEDICINE,
24, 19-19.
Author URL.
Strain WD, Chaturvedi N, Dockery F, Shiff R, Shore AC, Bulpitt CJ, Rajkumar C (2006). Increased arterial stiffness in Europeans and African Caribbeans with type 2 diabetes cannot be accounted for by conventional cardiovascular risk factors.
Am J Hypertens,
19(9), 889-896.
Abstract:
Increased arterial stiffness in Europeans and African Caribbeans with type 2 diabetes cannot be accounted for by conventional cardiovascular risk factors.
BACKGROUND: the impact of diabetes on vascular target organ damage (TOD) is not wholly explained by conventional risk factors. African Caribbeans have a greater prevalence of diabetes and some aspects of TOD. We hypothesized that arterial stiffness, an independent cardiovascular risk factor, would be more prevalent with diabetes and in African Caribbeans with diabetes than Europeans. METHODS: We measured pulse wave velocity (PWV), a measure of arterial stiffness, in the carotid-to-femoral, carotid-to-radial and femoral-to-dorsalis pedis segments, of men and women aged 40 to 65 years from the general population: 49 and 100 Europeans; 66 and 88 African Caribbeans with and without diabetes, respectively. RESULTS: Carotid-to-femoral PWV was faster (ie, arteries were stiffer) in diabetes and faster in African Caribbeans with diabetes compared with Europeans. These diabetes differences in PWV persisted after adjustment for conventional cardiovascular risk factors; Europeans without diabetes (95% confidence interval [CI]) 11.8 (11.4-12.3) versus with diabetes 13.3 (12.5-14.1) m/sec, P=.005; African Caribbeans without diabetes 12.6 (12.1-13.2) versus 14.0 (13.2-14.9) m/sec with diabetes, P=.008 (all fully adjusted). The ethnic difference in diabetes was largely attenuated by multivariate adjustment (P=.4). In the carotid-to-radial segment there was no ethnic difference in those without diabetes; however, African Caribbeans with diabetes had significantly faster PWV, which was not observed in Europeans (P for diabetes:ethnicity interaction=.001). CONCLUSIONS: Elastic arteries are stiffer in diabetes independent of traditional risk factors. African Caribbeans with diabetes have increased stiffness compared to Europeans, predominantly accounted for by blood pressure differences. Muscular arteries respond differently to diabetes in the two ethnic groups, which may reflect differences in remodeling.
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AShore, Bulpitt C, Chaturvedi N, Strain W (2005). Albumin excretion rate and cardiovascular risk: could the association be explained by early microvascular dysfunction. Diabetes, 54(6), 1816-1822.
Strain WD, Chaturvedi N, Bulpitt CJ, Rajkumar C, Shore AC (2005). Albumin excretion rate and cardiovascular risk: could the association be explained by early microvascular dysfunction?.
Diabetes,
54(6), 1816-1822.
Abstract:
Albumin excretion rate and cardiovascular risk: could the association be explained by early microvascular dysfunction?
Elevated albumin excretion rate (AER) independently predicts total and cardiovascular mortality in a variety of conditions, although the exact mechanisms are unknown. Laser Doppler fluximetry was used to study associations with risk factors and renal damage (AER calculated from a timed overnight urine collection) in 188 people without diabetes and 117 individuals with diabetes. Skin flow (flux) in response to arterial occlusion (ischemia) was measured. Three distinct patterns of postischemic peak flow were observed: 1) gradual rise to peak (normal), 2) nondominant early peak, and 3) dominant early peak. Those with a dominant early peak were more likely to have diabetes (P = 0.01), hypertension (P = 0.001), and obesity (P < 0.001) and had a higher AER (12.6 microg/min [95% CI 7.8-20.2] vs. 7.2 [5.5-9.5] nondominant early peak group and 3.7 [3.2-4.1] normal group; P < 0.001 for trend). This could not be accounted for by conventional cardiovascular risk factors (P < 0.001 after adjustment). A rapid peak flow response after ischemia is associated with an elevated AER and increased cardiovascular risk. This may represent shared mechanistic pathways and causative or con-sequential changes in the microvasculature and supports the hypothesis that microvascular dysfunction may contribute to large vessel pathophysiology.
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Strain WD, Chaturvedi N, Nihoyannopoulos P, Bulpitt CJ, Rajkumar C, Shore AC (2005). Differences in the association between type 2 diabetes and impaired microvascular function among Europeans and African Caribbeans.
Diabetologia,
48(11), 2269-2277.
Abstract:
Differences in the association between type 2 diabetes and impaired microvascular function among Europeans and African Caribbeans.
AIMS/HYPOTHESIS: Diabetes is associated with microvascular damage in all populations, but diabetic patients of Black African descent (African Caribbeans) have a greater risk of vascular target organ damage than would be anticipated for any given blood pressure level. We investigated whether this may be due to differences in the microvasculature. MATERIALS AND METHODS: to assess the maximum hyperaemic response to heating and the post-ischaemic response, Laser Doppler fluximetry was performed on 51 and 100 Europeans, and on 66 and 88 African Caribbeans with and without diabetes, respectively. Subjects were aged between 40 and 65 years and recruited from the general population. Echocardiographic interventricular septal thickness (IVST) was measured as a proxy for vascular target organ damage. RESULTS: in diabetic subjects of both ethnic groups, the maximum hyperaemic response and peak response to ischaemia were attenuated as compared to the corresponding non-diabetic subjects (p=0.08 for diabetic and 0.03 for non-diabetic Europeans; p=0.03 and 0.1 for African Caribbeans). Adjustment for cardiovascular risk factors, in particular insulin and blood pressure, abolished these differences in Europeans (p=0.8 for diabetic and 0.2 for non-diabetic Europeans), but not in African Caribbeans (p=0.03 and 0.05). CONCLUSIONS/INTERPRETATION: Persisting microvascular dysfunction in African Caribbeans may contribute to the increased risk of target organ damage observed in diabetes in this population. The weak contribution of conventional cardiovascular risk factors to these disturbances indicates that conventional therapeutic interventions may be less beneficial in these patients. There was a risk-factor-independent, inverse association between IVST and maximal hyperaemia. These ethnic differences in microvascular responses to temperature and arterial occlusion could account for increased target organ damage in African Caribbeans.
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Strain WD, Chaturvedi N, Shore A, Cruickshank JK, Heagerty AM (2005). Ethnic differences in microvascular structure and function [3] (multiple letters). Journal of Hypertension, 23(7), 1434-1436.
Strain WD, Chaturvedi N, Shore A (2005). Ethnic differences in microvascular structure and function.
J Hypertens,
23(7), 1434-1435.
Author URL.
Strain WD, Chaturvedi N, Leggetter S, Nihoyannopoulos P, Rajkumar C, Bulpitt CJ, Shore AC (2005). Ethnic differences in skin microvascular function and their relation to cardiac target-organ damage.
J Hypertens,
23(1), 133-140.
Abstract:
Ethnic differences in skin microvascular function and their relation to cardiac target-organ damage.
BACKGROUND: People of Black African descent have increased risks of vascular target-organ damage not explained by greater blood pressures. OBJECTIVE: to study ethnic differences in the microvasculature. DESIGN AND METHODS: Flow (flux) in microcirculatory skin vessels was assessed using laser Doppler fluximetry in 181 Afro-Caribbean and European men and women aged 40-65 years from the general population in London, UK. Flux in response to maximal heating (maximal hyperaemic response) was measured and minimum vascular resistance calculated. Peak flux and time to peak after an ischaemic stimulus were also measured. Target-organ damage was assessed using echocardiographic interventricular septal thickness (IVST). RESULTS: in men, maximum hyperaemic response was attenuated in Afro-Caribbeans [109 arbitrary units (au), 25th and 75th percentiles 101, 117] compared with Europeans [165 (155, 179) au; P = 0.008]. Minimum vascular resistance was greater in Afro-Caribbeans, significantly so in men [(1.22 (1.18, 1.28) au/mmHg compared with 0.80 (0.77, 0.83) au/mmHg; P = 0.006]. Peak ischaemic response was attenuated in Afro-Caribbean men and women compared with Europeans (35.6 au compared with 49.5 au; P < 0.001) and time to peak was prolonged (14.1 s compared with 12.5 s; P = 0.07). These ethnic differences could not be accounted for by standard cardiovascular risk factors. IVST was greater in Afro-Caribbeans than in Europeans. Minimum vascular resistance and peak response accounted for a small proportion of this ethnic difference, in addition to conventional factors. CONCLUSIONS: Afro-Caribbeans have poorer microvascular structure and function, unexplained by conventional risk factors, which may contribute to greater rates of vascular target-organ damage.
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Strain D, Bulpitt C, Chaturvedi N, Leggetter S (2004). Ethnic differences in vascular stiffness and relations to hypertensive target organ damage. Journal of Hypertension, 22(9), 1731-1737.
Chaturvedi N, Rajkumar C, Strain WD, Nihoyannopoulos P, Shore AC, Bulpitt CJ (2004). P-440: Ethnic differences in central and augmentation index; do they account for differing susceptibility to left ventricular hypertrophy. American Journal of Hypertension, 17(S1), 195a-195a.
Strain WD (2004). The use of recombinant human B-type natriuretic peptide (nesiritide) in the management of acute decompensated heart failure.
Int J Clin Pract,
58(11), 1081-1087.
Abstract:
The use of recombinant human B-type natriuretic peptide (nesiritide) in the management of acute decompensated heart failure.
Nesiritide is a synthetic human B-type natriuretic factor that has a balanced arterial and venous dilator effect, with natriuretic, diuretic, anti-aldosterone and antisympathetic action. It was launched in the US for the treatment of acute decompensated heart failure (ADHF) in August 2001 and, recently, in Switzerland and Israel. It has been demonstrated to provide more rapid and sustained haemodynamic stabilisation than glyceryl trinitrate and significant symptomatic improvement vs. placebo at 3 h, and to be safer than dobutamine. The main side effects associated with nesiritide therapy are asymptomatic and symptomatic hypotension, which are treated with dose reduction. When compared to dobutamine, the increased acquisition costs of nesiritide are completely offset by reduced intensity of hospital admissions and reduced readmission rate at 3 weeks.
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Strain W (2004). Who are we hurting? the hesitation by people of color. Positively aware : the monthly journal of the Test Positive Aware Network, 15(4), 23-24.
Strain WD, Lye M (2002). Chronic pain, bereavement and overdose in a depressed elderly woman.
Age Ageing,
31(3), 218-219.
Author URL.
Strain WD, Chaturvedi N (2002). The renin-angiotensin-aldosterone system and the eye in diabetes.
J Renin Angiotensin Aldosterone Syst,
3(4), 243-246.
Abstract:
The renin-angiotensin-aldosterone system and the eye in diabetes.
Diabetic retinopathy is the leading cause of blindness in the under 65s, and with the burden of disease case load expected to exceed 200 million worldwide within 10 years, much effort is being spent on prophylactic interventions. Early work focused on improving glycaemic control; however, with the publication of EURODIAB Controlled trial of Lisinopril in Insulin-dependent Diabetes (EUCLID) and United Kingdom Prospective Diabetes Study (UKPDS), the focus has recently moved to control of blood pressure and specifically the renin-angiotensin system (RAS). There is a large body of evidence for a local RAS within the eye that is activated in diabetes. This appears to be directly responsible, as well as indirectly through other mediators, for an increase in concentration of vascular endothelial growth factor (VEGF), a selective angiogenic and vasopermeability factor that is implicated in the pathogenesis of diabetic retinopathy. Inhibition of angiotensin-converting enzyme appears to reduce concentrations of VEGF, with a concurrent anti-proliferative effect independent of systemic VEGF levels or blood pressure. Angiotensin II (Ang II) Type 1 (AT(1)) receptor blockade has been shown to reduce neovascularisation independent of VEGF levels in animal models. This may be due to antagonism of activation of mitogen-activated protein kinase, which is a potent cellular proliferation stimulator, by Ang II, although this needs further evaluation.
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Gill G, Swift AC, Jones A, Strain D, Weston PJ (2001). Severe adrenal suppression by steroid nasal drops. J R Soc Med, 94, 350-351.
