Publications by authors named "Allan B Clark"

68 Publications

Modified early warning score and risk of mortality after acute stroke.

Clin Neurol Neurosurg 2021 Mar 6;202:106547. Epub 2021 Feb 6.

Institute of Applied Health Sciences, University of Aberdeen, AB25 2ZD, UK. Electronic address:

Objective: An accurate prediction tool may facilitate optimal management of patients with acute stroke from an early stage. We evaluated the association between admission modified early warning score (MEWS) and mortality in patients with acute stroke.

Method: Data from the Anglia Stroke Clinical Network Evaluation Study (ASCNES) were analysed. We evaluated the association between admission MEWS and four outcomes; in-patient, 7-day, 30-day and 1-year mortality. Logistic regression models were used to calculate the odds of all mortality timeframes, whereas Cox proportional hazards models were used to calculate mortality at 1 year. Five univariate and multivariate models were constructed, adjusting for confounders. Patients with a moderate (2-3) or high (≥4) scores were compared to patients with a low score (0-1).

Results: The study population consisted of 2006 patients. A total of 1196 patients had low MEWS, 666 had moderate MEWS and 144 had a high MEWS. A high MEWS was associated with increased mortality as an in-patient (OR 4.93, 95 % CI: 2.88-8.42), at 7 days (OR 7.53, 95 % CI: 4.24-13.38), at 30 days (OR 5.74, 95 % CI: 3.38-9.76) and 1-year (HR 2.52, 95 % CI 1.88-3.39). At 1 year, model 5 had a 1.02 OR (95 % CI 0.83-1.24) with moderate MEWS and 2.52 (95 % CI 1.88-3.39) with high MEWS.

Conclusion: Elevated MEWS on admission is a potential marker for acute-stroke mortality and may therefore be a useful risk prediction tool, able to guide clinicians attempting to prognosticate outcomes for patients with acute-stroke.
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http://dx.doi.org/10.1016/j.clineuro.2021.106547DOI Listing
March 2021

Effect of Co-trimoxazole (Trimethoprim-Sulfamethoxazole) vs Placebo on Death, Lung Transplant, or Hospital Admission in Patients With Moderate and Severe Idiopathic Pulmonary Fibrosis: The EME-TIPAC Randomized Clinical Trial.

JAMA 2020 12;324(22):2282-2291

MRC Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom.

Importance: Idiopathic pulmonary fibrosis (IPF) has a poor prognosis and limited treatment options. Patients with IPF have altered lung microbiota, with bacterial burden within the lungs associated with mortality; previous studies have suggested benefit with co-trimoxazole (trimethoprim-sulfamethoxazole).

Objective: To determine the efficacy of co-trimoxazole in patients with moderate and severe IPF.

Design, Setting, And Participants: Double-blind, placebo-controlled, parallel randomized trial of 342 patients with IPF, breathlessness (Medical Research Council dyspnea scale score >1), and impaired lung function (forced vital capacity ≤75% predicted) conducted in 39 UK specialist interstitial lung disease centers between April 2015 (first patient visit) and April 2019 (last patient follow-up).

Interventions: Study participants were randomized to receive 960 mg of oral co-trimoxazole twice daily (n = 170) or matched placebo (n = 172) for between 12 and 42 months. All patients received 5 mg of folic acid orally once daily.

Main Outcomes And Measures: The primary outcome was time to death (all causes), lung transplant, or first nonelective hospital admission. There were 15 secondary outcomes, including the individual components of the primary end point respiratory-related events, lung function (forced vital capacity and gas transfer), and patient-reported outcomes (Medical Research Council dyspnea scale, 5-level EuroQol 5-dimension questionnaire, cough severity, Leicester Cough Questionnaire, and King's Brief Interstitial Lung Disease questionnaire scores).

Results: Among 342 individuals who were randomized (mean age, 71.3 years; 46 [13%] women), 283 (83%) completed the trial. The median (interquartile range) duration of follow-up was 1.02 (0.35-1.73) years. Events per person-year of follow-up among participants randomized to the co-trimoxazole and placebo groups were 0.45 (84/186) and 0.38 (80/209), respectively, with a hazard ratio of 1.2 ([95% CI, 0.9-1.6]; P = .32). There were no statistically significant differences in other event outcomes, lung function, or patient-reported outcomes. Patients in the co-trimoxazole group had 696 adverse events (nausea [n = 89], diarrhea [n = 52], vomiting [n = 28], and rash [n = 31]) and patients in the placebo group had 640 adverse events (nausea [n = 67], diarrhea [n = 84], vomiting [n = 20], and rash [n = 20]).

Conclusions And Relevance: Among patients with moderate or severe IPF, treatment with oral co-trimoxazole did not reduce a composite outcome of time to death, transplant, or nonelective hospitalization compared with placebo.

Trial Registration: ISRCTN Identifier: ISRCTN17464641.
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http://dx.doi.org/10.1001/jama.2020.22960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724556PMC
December 2020

Seasonality of stroke: Winter admissions and mortality excess: A Thailand National Stroke population database study.

Clin Neurol Neurosurg 2020 Dec 2;199:106261. Epub 2020 Oct 2.

Ageing Clinical and Experimental Research Group, Institute of Applied Health Sciences, School of Medicine, Medical Sciences & Nutrition, University of Aberdeen, Aberdeen, AB252ZD, UK. Electronic address:

Objectives: We examined the existence and potential burden of seasonality of stroke admissions and mortality within a tropical climate using cohort data collected between 1 st November 2003 and 31 st October 2012.

Patients And Methods: In a prospective cohort of hospitalised stroke patients from the catchment of ∼75 % of the Thai population (n = 569,307; mean SD age = 64(14.5)), incident stroke admissions, in-hospital mortality, prolonged hospitalisations, and stroke related complications by season were determined. Rates of incident stroke admissions by month and season were plotted. Winter excess indexes for study outcomes expressed as a percentage were calculated. Using logistic regression we examined the association between winter admission and in-hospital mortality (non-winter admission as reference) adjusting for age, sex, stroke type, year of admission, and presence of pre-existing comorbidities.

Results: We observed a winter excess in mortality during hospitalisation (+10.3 %) and prolonged length of stay (+7.3 %). Respective winter excess indexes for dyslipidaemias, arrhythmias, anaemia, and alcohol related disorders in patients that died during hospitalisation were +1.4 %, +6.2 %, +0.2 %, +1.5 %. In these patients, respective winter excess indexes for post-stroke complications of pneumonia and sepsis were +6.7 % and +3.2 %. In fully adjusted analyses, winter admission (compared to non-winter admission) was associated with increased odds of in-hospital mortality (OR (95 % CI) = 1.023 (1.006-1.040)).

Conclusions: We provide robust evidence for the existence of an excess in winter stroke admissions and subsequent in-hospital deaths within a tropical region.
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http://dx.doi.org/10.1016/j.clineuro.2020.106261DOI Listing
December 2020

Revascularisation therapies improve the outcomes of ischemic stroke patients with atrial fibrillation and heart failure.

Int J Cardiol 2021 Feb 3;324:205-213. Epub 2020 Oct 3.

Keele Cardiovascular Research Group, Centre for Prognosis Research, Institute for Primary Care and Health Sciences, Keele University, Stoke-on-Trent, United Kingdom; Institute of Applied Health Sciences, School of Medicine, Medical Sciences & Nutrition, University of Aberdeen, United Kingdom; Norwich Medical School, University of East Anglia, Norwich, United Kingdom. Electronic address:

Background: Atrial fibrillation (AF) and heart failure (HF) carry a poor prognosis in acute ischaemic stroke (AIS). The impact of revascularisation therapies on outcomes in these patients is not fully understood.

Method: National Inpatient Sample (NIS) AIS admissions (January 2004-September 2015) were included (n = 4,597,428). Logistic regressions analysed the relationship between exposures (neither AF nor HF-reference, AF-only, HF-only, AF + HF) and outcomes (in-hospital mortality, length-of-stay >median and moderate-to-severe disability on discharge), stratifying by receipt of intravenous thrombolysis (IVT) or endovascular thrombectomy (ET).

Results: 69.2% patients had neither AF nor HF, 16.5% had AF-only, 7.5% had HF-only and 6.7% had AF + HF. 5.04% and 0.72% patients underwent IVT and/or ET, respectively. AF-only and HF-only were each associated with 75-85% increase in the odds of in-hospital mortality. AF + HF was associated with greater than two-fold increase in mortality. Patients with AF-only, HF-only or AF + HF undergoing IVT had better or at least similar in-hospital outcomes compared to their counterparts not undergoing IVT, except for prolonged hospitalisation. Patients undergoing ET with AF-only, HF-only or AF + HF had better (in-hospital mortality, discharge disability, all-cause bleeding) or at least similar (length-of-stay) outcomes to their counterparts not undergoing ET. Compared to AIS patients without AF, AF patients had approximately 50% and more than two-fold increases in the likelihood of receiving IVT or ET, respectively.

Conclusions: We confirmed the combined and individual impact of co-existing AF or HF on important patient-related outcomes. Revascularisation therapies improve these outcomes significantly in patients with these comorbidities.
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http://dx.doi.org/10.1016/j.ijcard.2020.09.076DOI Listing
February 2021

Infective endocarditis is associated with worse outcomes in stroke: A Thailand National Database Study.

Int J Clin Pract 2020 Nov 1;74(11):e13614. Epub 2020 Sep 1.

Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, UK.

Background: There is lack of data on the association between infective endocarditis (IE) and outcomes of mortality and complications in stroke. We aimed to compare characteristics and outcomes of stroke patients with and without IE.

Methods: We retrospectively examined the above association using data obtained from an insurance database which covers ~75% of the Thai population. All hospitalised strokes between 8 January 2003 and 31 December 2013 were included in the current study. Characteristics and outcomes were compared between stroke patients with or without IE, and then between two main stroke types. Multiple logistic regression models including propensity score-matched analyses were constructed to assess study outcomes controlling for age, sex, stroke type and comorbidities.

Results: A total of 590 115 stroke patients (mean (SD) age = 64.2 ± 13.7 years; ischaemic = 51.7%; haemorrhagic = 32.6%; undetermined = 15.7%) were included, of whom 2129 (0.36%) had stroke associated with IE. After adjustment, we found that IE was significantly associated with the following complications: arrhythmias (adjusted odds ratio (95% CI) 6.94 (6.29-7.66)), sepsis (1.24 (1.01-1.52)), pneumonia (1.34 (1.17-1.53)), respiratory failure (1.43 (1.24-1.66)) and in-hospital mortality (1.29 (1.13-1.47)) (P for all <.001). Patients with haemorrhagic stroke with IE had poorer outcomes for in-hospital mortality and respiratory failure compared with their counterparts with ischaemic stroke. Propensity score-matched analysis showed similar results.

Conclusions: Our results suggest that stroke patients with IE differ from that of the general stroke population and these patients have worse outcomes. Future studies are needed to determine the best treatment strategies for stroke patients with IE.
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http://dx.doi.org/10.1111/ijcp.13614DOI Listing
November 2020

Association of chronic kidney disease with outcomes in acute stroke.

Acta Neurol Belg 2020 Jul 13. Epub 2020 Jul 13.

ACER, School of Medicine, Medical Sciences and Nutrition, Institute of Applied Health Sciences, University of Aberdeen Foresthill, Room 4.013 Polwarth Building, Aberdeen, AB25 2ZD, Scotland, UK.

Previous studies have found an association between chronic kidney disease and poor outcomes in stroke patients. However, there is a paucity of literature evaluating this association by stroke type. We therefore aimed to explore the association between CKD and stroke outcomes according to type of stroke. The data consisting of 594,681 stroke patients were acquired from Universal Coverage Health Security Insurance Scheme Database in Thailand. Binary logistic regression was used to assess the relationship of CKD and outcomes, which were as follows; in-hospital mortality, long length of stay (>3 days), pneumonia, sepsis, respiratory failure and myocardial infarction. Results: after fully adjusting for covariates, CKD was associated with increased odds of in-hospital mortality in patients with ischemic (OR 1.32; 95% CI = 1.27-1.38), haemorrhagic (OR 1.31; 95% CI = 1.24-1.39), and other undetermined stroke type (OR 1.44; 95% CI = 1.21-1.73). CKD was found to be associated with increased odds of pneumonia, sepsis, respiratory failure and myocardial infarction in ischaemic stroke. While CKD was found to be associated with increase odds of sepsis, respiratory failure, and myocardial infarction, decrease odds of pneumonia was observed in patients with haemorrhagic stroke. In other undetermined stroke type, CKD was found to only be associated with increase odds of sepsis and respiratory failure, while there is no significant association of CKD and increase or decrease odds with pneumonia and myocardial infarction. CKD was associated with poor outcomes in all stroke types. CKD should be considered as part of stroke prognosis as well as identifying at risk patient population for in-hospital complications.
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http://dx.doi.org/10.1007/s13760-020-01416-0DOI Listing
July 2020

Impact of Diabetes on Complications, Long Term Mortality and Recurrence in 608,890 Hospitalised Patients with Stroke.

Glob Heart 2020 02 6;15(1). Epub 2020 Feb 6.

Ageing Clinical and Experimental Research (ACER) Team, Institute of Applied Health Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK.

Background: Patients with diabetes mellitus (DM) have been found to be at an increased risk of suffering a stroke. However, research on the impact of DM on stroke outcomes is limited.

Objectives: We aimed to examine the influence of DM on outcomes in ischaemic (IS) and haemorrhagic stroke (HS) patients.

Methods: We included 608,890 consecutive stroke patients from the Thailand national insurance registry. In-hospital mortality, sepsis, pneumonia, acute kidney injury (AKI), urinary tract infection (UTI) and cardiovascular events were evaluated using logistic regressions. Long-term analysis was performed on first-stroke patients with a determined pathology (n = 398,663) using Royston-Parmar models. Median follow-ups were 4.21 and 4.78 years for IS and HS, respectively. All analyses were stratified by stroke sub-type.

Results: Mean age (SD) was 64.3 (13.7) years, 44.9% were female with 61% IS, 28% HS and 11% undetermined strokes. DM was associated with in-hospital death, pneumonia, sepsis, AKI and cardiovascular events (odds ratios ranging from 1.13-1.78, p < 0.01) in both stroke types. In IS, DM was associated with long-term mortality and recurrence throughout the follow-up: HR (99% CI) at t = 4108 days: 1.54 (1.27, 1.86) and HR (99% CI) = 1.27(1.23,1.32), respectively. In HS, HR (t = 4108 days) for long-term mortality was 2.10 (1.87, 2.37), significant after day 14 post-discharge. HR (t = 455) for long-term recurrence of HS was 1.29 (1.09, 1.53), significant after day 116 post-discharge.

Conclusions: Regardless of stroke type, DM was associated with in-hospital death and complications, long-term mortality and stroke recurrence.
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http://dx.doi.org/10.5334/gh.364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218766PMC
February 2020

Parkinson's disease and patient related outcomes in stroke: A matched cohort study.

J Stroke Cerebrovasc Dis 2020 Jul 10;29(7):104826. Epub 2020 May 10.

Ageing Clinical and Experimental Research (ACER) Team, Institute of Applied Health Sciences, School of Medicine, Medical Sciences & Nutrition, Foresterhill, University of Aberdeen, Aberdeen, United Kingdom. Electronic address:

Objective: To evaluate post-stroke outcomes in patients with Parkinson's disease (PD).

Methods: A matched cohort study was performed. Stroke patients with PD and non-PD controls were extracted from the Thailand Universal Insurance Database. Logistic regressions were used to evaluate the association between PD and in-hospital outcomes (mortality and complications). The PD-associated long-term mortality was evaluated using Royston-Parmar models.

Results: A total of 1967 patients with PD were identified between 2003 and 2015 and matched to controls (1:4) by age, sex, admission year, and stroke type. PD patients had decreased odds of in-hospital death: OR (95% CI) 0.66 (0.52 - 0.84) and 0.61 (0.43 - 0.85) after ischaemic and haemorrhagic strokes, respectively. PD was associated with a length-of-stay greater than median (4 days) after both stroke types: 1.37 (1.21 - 1.56) and 1.45 (1.05 - 2.00), respectively. Ischaemic stroke patients with PD also had increased odds of developing pneumonia, sepsis and AKI: 1.52 (1.2 - 1.83), 1.54 (1.16 - 2.05), and 1.33 (1.02 - 1.73). In haemorrhagic stroke patients, PD was associated with pneumonia: 1.89 (1.31 - 2.72). Survival analyses showed that PD was protective against death in the short term (HR=0.66; 95% CI 0.53-0.83 ischaemic, and HR=0.50; 95% CI 0.37 - 0.68 haemorrhagic stroke), but leads to an increased mortality risk approximately 1 and 3 months after ischaemic and haemorrhagic stroke, respectively.

Conclusion: PD is associated with a reduced mortality risk during the first 2-4 weeks post-admission but an increased risk thereafter, in addition to increased odds of in-hospital complications and prolonged hospitalisation.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.104826DOI Listing
July 2020

Design and rationale of a multi-center, pragmatic, open-label randomized trial of antimicrobial therapy - the study of clinical efficacy of antimicrobial therapy strategy using pragmatic design in Idiopathic Pulmonary Fibrosis (CleanUP-IPF) clinical trial.

Respir Res 2020 Mar 12;21(1):68. Epub 2020 Mar 12.

Division of Pulmonary Medicine, Weill-Cornell Medical Center, Cornell University, New York, NY, USA.

Compelling data have linked disease progression in patients with idiopathic pulmonary fibrosis (IPF) with lung dysbiosis and the resulting dysregulated local and systemic immune response. Moreover, prior therapeutic trials have suggested improved outcomes in these patients treated with either sulfamethoxazole/ trimethoprim or doxycycline. These trials have been limited by methodological concerns. This trial addresses the primary hypothesis that long-term treatment with antimicrobial therapy increases the time-to-event endpoint of respiratory hospitalization or all-cause mortality compared to usual care treatment in patients with IPF. We invoke numerous innovative features to achieve this goal, including: 1) utilizing a pragmatic randomized trial design; 2) collecting targeted biological samples to allow future exploration of 'personalized' therapy; and 3) developing a strong partnership between the NHLBI, a broad range of investigators, industry, and philanthropic organizations. The trial will randomize approximately 500 individuals in a 1:1 ratio to either antimicrobial therapy or usual care. The site principal investigator will declare their preferred initial antimicrobial treatment strategy (trimethoprim 160 mg/ sulfamethoxazole 800 mg twice a day plus folic acid 5 mg daily or doxycycline 100 mg once daily if body weight is < 50 kg or 100 mg twice daily if ≥50 kg) for the participant prior to randomization. Participants randomized to antimicrobial therapy will receive a voucher to help cover the additional prescription drug costs. Additionally, those participants will have 4-5 scheduled blood draws over the initial 24 months of therapy for safety monitoring. Blood sampling for DNA sequencing and genome wide transcriptomics will be collected before therapy. Blood sampling for transcriptomics and oral and fecal swabs for determination of the microbiome communities will be collected before and after study completion. As a pragmatic study, participants in both treatment arms will have limited in-person visits with the enrolling clinical center. Visits are limited to assessments of lung function and other clinical parameters at time points prior to randomization and at months 12, 24, and 36. All participants will be followed until the study completion for the assessment of clinical endpoints related to hospitalization and mortality events. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02759120.
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http://dx.doi.org/10.1186/s12931-020-1326-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7069004PMC
March 2020

Self-Monitoring and Management of Blood Pressure in Patients with Stroke or TIA: An Economic Evaluation of TEST-BP, A Randomised Controlled Trial.

Pharmacoecon Open 2020 Sep;4(3):511-517

Ageing and Stroke Medicine, Norwich Medical School, University of East Anglia, Norwich, UK.

Background: Prevention of secondary stroke following initial ictus is an important focus of after-stroke care. Blood pressure (BP) is a key risk factor, so usual care following stroke or transient ischaemic attack includes regular BP checks and monitoring of anti-hypertensive medication. This is traditionally carried out in primary care, but the evidence supporting self-monitoring and self-guided management of BP in the general population with hypertension is growing.

Objective: Our objective was to estimate the cost effectiveness of treatment as usual (TAU) versus (1) self-monitoring of BP (S-MON) and (2) self-monitoring and guided self-management of anti-hypertensive medication (S-MAN).

Methods: This was a within-trial economic evaluation of a randomised controlled trial estimating the incremental cost per 1 mmHg BP reduction and per quality-adjusted life-year (QALY) gained over a 6-month time horizon from the perspective of the UK National Health Service (NHS).

Results: Data were evaluable for 140 participants. Costs per patient were £473, £853 and £1035; mean reduction in systolic BP (SBP) was 3.6, 6.7 and 6.1 mmHg, and QALYs accrued were 0.427, 0.422 and 0.423 for TAU, S-MON and S-MAN, respectively. No statistically significant differences in incremental costs or outcomes were detected. On average, S-MAN was dominated or extended dominated. The incremental cost per 1 mmHg BP reduction from S-MON versus TAU was £137.

Conclusion: On average, S-MAN is an inefficient intervention. S-MON may be cost effective, depending on the willingness to pay for a 1 mmHg BP reduction, although it yielded fewer QALYs over the within-trial time horizon. Decision modelling is required to explore the longer-term costs and outcomes.
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http://dx.doi.org/10.1007/s41669-020-00196-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426342PMC
September 2020

Anaemia and incidence of post stroke dementia.

Clin Neurol Neurosurg 2020 04 23;191:105688. Epub 2020 Jan 23.

Norwich Medical School, University of East Anglia, UK; Norfolk and Norwich University Hospital, Norwich, UK.

Objectives: To assess the impact of anaemia on incidence of post-stroke dementia.

Patients And Methods: We used data from a UK regional stroke register. To be eligible, patient must have survived to discharge and had anaemia by WHO criteria. Dementia status and other prevalent co-morbidities were assessed using ICD-10 codes. Patients were followed till May 2015 (mean follow-up 3.7 years, total person years = 27,769). Hazard Ratio for incident dementia was calculated using Cox-proportional hazards model controlling for potential confounders. Fine and Gray model was additionally constructed using mortality as the competing risk.

Results: A total of 7454 stroke patients were included with mean age SD of 75.912.3 years 50.2 % men). Those with anaemia were older, has higher disability and co-morbidity burden prior to stroke. We observed a large amount of variation in the dementia incidence rates over time and that the hazard ratio increased every year. The significant association between anaemia and dementia incidence was lost after controlling for pre-stroke Modified Rankin score (HR1.17(0.97,1.40)). With every 20 g/dL increase in Hb was associated with a significant reduction in the risk of dementia after adjustment for age, sex, stroke factors and disability but lost significance after adjustment for vascular risk factors. Competing risk analyses showed similar results.

Conclusion: Whilst we found no evidence of anaemia as a risk factor for post-stroke dementia, the findings may be limited by potential under recognition of post stroke dementia.
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http://dx.doi.org/10.1016/j.clineuro.2020.105688DOI Listing
April 2020

Does prior antithrombotic therapy influence recurrence and bleeding risk in stroke patients with atrial fibrillation or atrial flutter?

Eur J Prev Cardiol 2020 05 3;27(7):729-737. Epub 2019 Sep 3.

Ageing Clinical and Experimental Research (ACER) Team, University of Aberdeen, UK.

Background: Whilst antithrombotic therapy is recommended in people with atrial fibrillation, little is known about the survival benefits of antithrombotic treatment in those with both high ischaemic and bleeding risk scores. We aim to describe the distribution of these risk scores in those with a prior diagnosis of atrial fibrillation who have suffered stroke and to determine the net clinical benefit of antithrombotic treatment.

Methods: We used regional stroke register data in the UK. Patients with a prior diagnosis of atrial fibrillation and ischaemic or haemorrhagic stroke patients were selected and their ischaemic stroke risk score (CHADS-VAS) and bleeding risk score (HEMORRHAGES) scores retrospectively calculated. Logistic regression and Cox proportional hazards models were constructed to determine the association between antithrombotic therapy prior to stroke and in-hospital and long-term mortality.

Results: A total of 1928 stroke patients (mean age 81.3 years (standard deviation 8.5), 56.8% women) with prior atrial fibrillation were included. Of these, 1761 (91.3%) suffered ischaemic stroke. The most common phenotype (64%) was of those with both high CHADS-VAS (≥2) and high HEMORRHAGES score (≥4). In our fully adjusted model, patients on antithrombotic treatment with both high ischaemic and bleeding risk had a significant reduction in odds of 31% for in-hospital mortality (odds ratio 0.69 (95% confidence interval 0.48-1.00:  = 0.049)) and 17% relative risk reduction for long-term mortality (hazard ratio 0.83 (95% confidence interval 0.71-0.97:  = 0.02)).

Conclusions: Our study suggests that antithrombotic treatment has a prognostic benefit following incident stroke in those with both high ischaemic risk and high bleeding risk. This should be considered when choosing treatment options in this group of patients.
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http://dx.doi.org/10.1177/2047487319871709DOI Listing
May 2020

Plasma Vitamin C Levels: Risk Factors for Deficiency and Association with Self-Reported Functional Health in the European Prospective Investigation into Cancer-Norfolk.

Nutrients 2019 Jul 9;11(7). Epub 2019 Jul 9.

Ageing Clinical & Experimental Research Group, Institute of Applied Health Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.

Background: To investigate the demographic and lifestyles factors associated with vitamin C deficiency and to examine the association between plasma vitamin C level and self-reported physical functional health.

Methods: A population-based cross-sectional study using the European Prospective Investigation into Cancer-Norfolk study. Plasma vitamin C level < 11 µmol/L indicated vitamin C deficiency. Unconditional logistic regression models assessed the association between vitamin C deficiency and potential risk factors. Associations between quartiles of vitamin C and self-reported functional health measured by the 36-item short-form questionnaire (SF-36) were assessed.

Results: After adjustment, vitamin C deficiency was associated with older age, being male, lower physical activity, smoking, more socially deprived area (Townsend index) and a lower educational attainment. Compared to the highest, those in the lowest quartile of vitamin C were more likely to score in the lowest decile of physical function (adjusted odds ratio (aOR): 1.43 (95%CI: 1.21-1.70)), bodily pain (aOR: 1.29 (95% CI: 1.07-1.56)), general health (aOR: 1.4 (95%CI: 1.18-1.66)), and vitality (aOR: 1.23 (95%CI: 1.04-1.45)) SF-36 scores.

Conclusions: Simple public health interventions should be aimed at populations with risk factors for vitamin C deficiency. Poor self-reported functional health was associated with lower plasma vitamin C levels, which may reflect symptoms of latent scurvy.
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http://dx.doi.org/10.3390/nu11071552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6682997PMC
July 2019

Impact of heart failure on stroke mortality and recurrence.

Heart Asia 2019 20;11(1):e011139. Epub 2019 Apr 20.

Ageing Clinical and Experimental Research Team, Institute of Applied Health Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK.

Objective: We aimed to examine the impact of heart failure (HF) on stroke mortality (in-hospital and postdischarge) and recurrence in a national stroke cohort from Thailand.

Methods: We used a large, insurance-based database including all stroke admissions in the public health sector in Thailand between 2004 and 2015. Logistic and Royston-Parmar regressions were used to quantify the effect of HF on in-hospital and long-term outcomes, respectively. All models were adjusted for age, sex and comorbidities and stratified by stroke type: acute ischaemic stroke (AIS) or intracerebral haemorrhage (ICH). Multistate models were constructed using flexible survival techniques to predict the impact of HF on the disease course of a patient with stroke (baseline-[recurrence]-death). Only first-ever cases of AIS or ICH were included in the multistate analysis.

Results: 608 890 patients (mean age 64.29±13.72 years, 55.07% men) were hospitalised (370 527 AIS, 173 236 ICH and 65 127 undetermined pathology). There were 398 663 patients with first-ever AIS and ICH. Patients were followed up for a median (95% CI) of 4.47 years (4.45 to 4.49). HF was associated with an increase in postdischarge mortality in AIS (HR [99% CI] 1.69 [1.64 to 1.74]) and ICH (2.59 [2.07 to 3.26]). HF was not associated with AIS recurrence, while ICH recurrence was only significantly increased within the first 3 years after discharge (1.79 [1.18 to 2.73]).

Conclusions: HF increases the risk of mortality in both AIS and ICH. We are the first to report on high-risk periods of stroke recurrence in patients with HF with ICH. Specific targeted risk reduction strategies may have significant clinical impact for mortality and recurrence in stroke.
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http://dx.doi.org/10.1136/heartasia-2018-011139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6560925PMC
April 2019

Can goal-setting for patients with multimorbidity improve outcomes in primary care? Cluster randomised feasibility trial.

BMJ Open 2019 06 3;9(6):e025332. Epub 2019 Jun 3.

Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, UK.

Introduction: Goal-setting is recommended for patients with multimorbidity, but there is little evidence to support its use in general practice.

Objective: To assess the feasibility of goal-setting for patients with multimorbidity, before undertaking a definitive trial.

Design And Setting: Cluster-randomised controlled feasibility trial of goal-setting compared with control in six general practices.

Participants: Adults with two or more long term health conditions and at risk of unplanned hospital admission.

Interventions: General practitioners (GPs) underwent training and patients were asked to consider goals before an initial goal-setting consultation and a follow-up consultation 6 months later. The control group received usual care planning.

Outcome Measures: Health-related quality of life (EQ-5D-5L), capability (ICEpop CAPability measure for Older people), Patient Assessment of Chronic Illness Care and healthcare use. All consultations were video-recorded or audio-recorded, and focus groups were held with participating GPs and patients.

Results: Fifty-two participants were recruited with a response rate of 12%. Full follow-up data were available for 41. In the goal-setting group, mean age was 80.4 years, 54% were female and the median number of prescribed medications was 13, compared with 77.2 years, 39% female and 11.5 medications in the control group. The mean initial consultation time was 23.0 min in the goal-setting group and 19.2 in the control group. Overall 28% of patient participants had no cognitive impairment. Participants set between one and three goals on a wide range of subjects, such as chronic disease management, walking, maintaining social and leisure interests, and weight management. Patient participants found goal-setting acceptable and would have liked more frequent follow-up. GPs unanimously liked goal-setting and felt it delivered more patient-centred care, and they highlighted the importance of training.

Conclusions: This goal-setting intervention was feasible to deliver in general practice. A larger, definitive study is needed to test its effectiveness.

Trial Registration Number: ISRCTN13248305; Post-results.
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http://dx.doi.org/10.1136/bmjopen-2018-025332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6561432PMC
June 2019

Myocardial infarction after acute ischaemic stroke: Incidence, mortality and risk factors.

Acta Neurol Scand 2019 Sep 17;140(3):219-228. Epub 2019 Jun 17.

Norfolk and Norwich University Hospital, Norwich, UK.

Objectives: To determine the risk factor profiles associated with post-acute ischaemic stroke (AIS) myocardial infarction (MI) over long-term follow-up.

Methods: This observational study includes prospectively identified AIS patients (n = 9840) admitted to a UK regional centre between January 2003 and December 2016 (median follow-up: 4.72 years). Predictors of post-stroke MI during follow-up were examined using logistic and Cox regression models for in-hospital and post-discharge events, respectively. MI incidence was determined using a competing risk non-parametric estimator. The influence of post-stroke MI on mortality was examined using Cox regressions.

Results: Mean age (SD) of study participants was 77.3 (12.2) years (48% males). Factors associated with in-hospital MI (OR [95% CI]) were increasing blood glucose (1.80 [1.17-2.77] per 10 mmol/L), total leucocyte count (1.25 [1.01-1.54] per 10 × 10 /L) and CRP (1.05 [1.02-1.08] per 10 mg/L increase). Age (HR [95% CI] = 1.03 [1.01-1.06]), coronary heart disease (1.59 [1.01-2.50]), chronic kidney disease (2.58 [1.44-4.63]) and cancers (1.76 [1.08-2.89]) were associated with incident MI between discharge and one-year follow-up. Age (1.02 [1.00-1.03]), diabetes (1.96 [1.38-2.65]), congestive heart failure (2.07 [1.44-2.99]), coronary heart disease (1.81 [1.31-2.50]), hypertension [1.86 (1.24-2.79)] and peripheral vascular disease (2.25 [1.40-3.63]) were associated with incident MI between 1 and 5 years after discharge. Diabetes (2.01 [1.09-3.72]), hypertension (3.69 [1.44-9.45]) and peripheral vascular disease (2.46 [1.02-5.98]) were associated with incident MI between 5 and 10 years after discharge. Cumulative MI incidence over 10 years was 5.4%. MI during all follow-up periods (discharge-1, 1-5, 5-10 years) was associated with increased risk of death (respective HR [95% CI] = 3.26 [2.51-4.15], 1.96 [1.58-2.42] and 1.92 [1.26-2.93]).

Conclusions: In conclusion, prognosis is poor in post-stroke MI. We highlight a range of potential areas to focus preventative efforts.
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http://dx.doi.org/10.1111/ane.13135DOI Listing
September 2019

Cognitive profile and determinants of poor cognition in people without dementia in Parkinson's disease.

Med J Islam Repub Iran 2019 4;33. Epub 2019 Feb 4.

Aging Clinical and Experimental Research (ACER) Team, School of Medicine, Medical Sciences, and Nutrition, University of Aberdeen, Aberdeen, UK.

The Montreal Cognitive Assessment (MoCA) has been recommended as a cognitive screening tool for clinical practice and research in Parkinson's disease (PD), yet no normative data have been published for MoCA in PD without dementia. We undertook a pooled secondary analysis of data from two studies (one cross-sectional design and one clinical trial) conducted in the East of England region. All participants were aged 18 years or over, met UK Brain Bank criteria for PD and did not have clinical dementia. Cognitive status was assessed using MoCA at baseline in both studies. The influences of age, gender, disease duration, medication load (LEDD) and mood (HADS) on cognition were examined using regression analysis. Data from 101 people with PD without dementia were available (mean age 71 years, 66% men). Median (IQR) MoCA was 25(22, 27). Age was found as the only predictor of MoCA in this sample. People aged over 71 had poorer MoCA (Beta=0.6 (95%CI 0.44, 0.82)) and an increased odds of MoCA <26 (Beta=0.29 (95%CI 0.12, 0.70)) as well as poorer scores on several MoCA sub-domains. We present the normative data for MoCA in people with PD without clinical dementia. Age appeared to be the only associated factor for lower level of cognition, suggestive of Mild cognitive impairment in PD (PD-MCI) in PD without clinical diagnosis of dementia.
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http://dx.doi.org/10.34171/mjiri.33.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6504994PMC
February 2019

Doctors Are Inconsistent in Estimating Survival after CPR and Are Not Using Such Predictions Consistently in Determining DNACPR Decisions.

Geriatrics (Basel) 2019 May 3;4(2). Epub 2019 May 3.

Leicester Medical School, College of Life Sciences, University of Leicester, Leicester LE1 7RH, UK.

: It is unclear whether doctors base their resuscitation decisions solely on their perceived outcome. Through the use of theoretical scenarios, we aimed to examine the 'do not attempt cardiopulmonary resuscitation' (DNACPR) decision-making. : A questionnaire survey was sent to consultants and specialty trainees across two Norfolk (UK) hospitals during December 2013. The survey included demographic questions and six clinical scenarios with varying prognosis. Participants were asked if they would resuscitate the patient or not. Identical scenarios were then shown in a different order and doctors were asked to quantify patients' estimated chance of survival. : A total of 137 individuals (mean age 41 years (SD 7.9%)) responded. The response rate was 69%. Approximately 60% were consultants. We found considerable variation in clinician estimates of median chance of survival. In three out of six of our scenarios, the survival estimated varied from <1% to 95%. There was a statistically significant difference identified in the estimated median survival between those clinicians who would or would not resuscitate in four of the six scenarios presented. : This study has highlighted the wide variation between clinicians in their estimates of likely survival and little concordance between clinicians over their resuscitation decisions. The diversity in clinician decision-making should be explored further.
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http://dx.doi.org/10.3390/geriatrics4020033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6631017PMC
May 2019

Pneumonia and Risk of Serious Adverse Outcomes in Hospitalized Strokes in Thailand.

J Stroke Cerebrovasc Dis 2019 Jun 4;28(6):1448-1454. Epub 2019 Apr 4.

Ageing Clinical and Experimental Research (ACER), Institute of Applied Health Sciences, School of Medicine, Medical Sciences & Nutrition, University of Aberdeen, Foresthill, Aberdeen, United Kingdom. Electronic address:

Background: The impact of stroke associated pneumonia (SAP) on stroke complications is not well understood; we aimed to study the association between SAP and adverse outcomes including in-hospital mortality, prolonged length of stay and the risk of developing common serious complications (sepsis, respiratory failure, and convulsions).

Methods: We retrospectively analyzed data from a cohort of 610,668 stroke patients drawn from the Universal Coverage Health Security Scheme (a national insurance database) in Thailand which covers ∼80% of the Thai population. Patients were hospitalized between October 2004 and January 2013.

Results: Pneumonia was present in 9.6 % (n = 58,586) of patients. Aspiration pneumonia was present in 6.2% (n = 38,060) and nonaspiration pneumonia in 3.4% (n = 20,526). After adjusting for age, sex, stroke type, and comorbidities, patients with SAP had significantly higher odds of in-hospital mortality (odds ratio [OR] 2.90: 2.83-2.96), long length of stay (OR 13.11: 12.83-13.40), sepsis (OR 8.49: 8.22-8.76), respiratory failure (OR 4.37: 4.27-4.48), and convulsions (OR 2.09: 2.00-2.17). On subanalysis, patients with nonaspiration pneumonia were found to have higher odds of adverse outcomes compared to aspiration pneumonia; the corresponding ORs (95% confidence interval) for above outcomes were 1.25 (1.21-1.30), 2.40 (2.32-2.49), 1.34 (1.28-1.40), 1.80 (1.73-1.88), and 1.19 (1.11-1.28), respectively.

Conclusions: SAP is associated with higher odds of inpatient mortality, long length of stay, and risk of developing serious stroke complications. Nonaspiration pneumonia is associated with significantly higher likelihood of adverse outcomes compared to aspiration pneumonia in this patient population. Early identification and treatment of SAP is vital in reducing adverse outcomes in acute stroke.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2019.03.024DOI Listing
June 2019

Pneumonia and Risk of Serious Adverse Outcomes in Hospitalized Strokes in Thailand.

J Stroke Cerebrovasc Dis 2019 Jun 4;28(6):1448-1454. Epub 2019 Apr 4.

Ageing Clinical and Experimental Research (ACER), Institute of Applied Health Sciences, School of Medicine, Medical Sciences & Nutrition, University of Aberdeen, Foresthill, Aberdeen, United Kingdom. Electronic address:

Background: The impact of stroke associated pneumonia (SAP) on stroke complications is not well understood; we aimed to study the association between SAP and adverse outcomes including in-hospital mortality, prolonged length of stay and the risk of developing common serious complications (sepsis, respiratory failure, and convulsions).

Methods: We retrospectively analyzed data from a cohort of 610,668 stroke patients drawn from the Universal Coverage Health Security Scheme (a national insurance database) in Thailand which covers ∼80% of the Thai population. Patients were hospitalized between October 2004 and January 2013.

Results: Pneumonia was present in 9.6 % (n = 58,586) of patients. Aspiration pneumonia was present in 6.2% (n = 38,060) and nonaspiration pneumonia in 3.4% (n = 20,526). After adjusting for age, sex, stroke type, and comorbidities, patients with SAP had significantly higher odds of in-hospital mortality (odds ratio [OR] 2.90: 2.83-2.96), long length of stay (OR 13.11: 12.83-13.40), sepsis (OR 8.49: 8.22-8.76), respiratory failure (OR 4.37: 4.27-4.48), and convulsions (OR 2.09: 2.00-2.17). On subanalysis, patients with nonaspiration pneumonia were found to have higher odds of adverse outcomes compared to aspiration pneumonia; the corresponding ORs (95% confidence interval) for above outcomes were 1.25 (1.21-1.30), 2.40 (2.32-2.49), 1.34 (1.28-1.40), 1.80 (1.73-1.88), and 1.19 (1.11-1.28), respectively.

Conclusions: SAP is associated with higher odds of inpatient mortality, long length of stay, and risk of developing serious stroke complications. Nonaspiration pneumonia is associated with significantly higher likelihood of adverse outcomes compared to aspiration pneumonia in this patient population. Early identification and treatment of SAP is vital in reducing adverse outcomes in acute stroke.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2019.03.024DOI Listing
June 2019

Plasma vitamin C concentrations and risk of incident respiratory diseases and mortality in the European Prospective Investigation into Cancer-Norfolk population-based cohort study.

Eur J Clin Nutr 2019 11 31;73(11):1492-1500. Epub 2019 Jan 31.

Clinical Gerontology Unit, Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, Cambridge, UK.

Background/objectives: Cancerous and non-cancerous respiratory diseases are common and contribute significantly to global disease burden. We aim to quantify the association between plasma vitamin C concentrations as an indicator of high fruit and vegetable consumption and the risk of incident respiratory diseases and associated mortality in a general population.

Subjects/methods: Nineteen thousand three hundred and fifty-seven men and women aged 40-79 years without prevalent respiratory diseases at the baseline (1993-1997) and participating in the European Prospective Investigation into Cancer (EPIC)-Norfolk study in the United Kingdom were followed through March 2015 for both incidence and mortality from respiratory diseases.

Results: There were a total of 3914 incident events and 407 deaths due to any respiratory diseases (excluding lung cancers), 367 incident lung cancers and 280 lung cancer deaths during the follow-up (total person-years >300,000 years). Cox's proportional hazards models showed that persons in the top quartiles of baseline plasma vitamin C concentrations had a 43% lower risk of lung cancer (hazard ratio (HR) 0.57; 95% confidence interval (CI): 0.41-0.81) than did those in the bottom quartile, independently of potential confounders. The results are similar for any non-cancerous respiratory diseases (HR 0.85; 0.77-0.95), including chronic respiratory diseases (HR 0.81; 0.69-0.96) and pneumonia (HR 0.70; 0.59-0.83). The corresponding values for mortality were 0.54 (0.35-0.81), 0.81 (0.59-1.12), 0.85 (0.44-1.66) and 0.61 (0.37-1.01), respectively. Confining analyses to non-smokers showed 42% and 53% risk reduction of non-smoking-related lung cancer incidence and death.

Conclusions: Higher levels of vitamin C concentrations as a marker of high fruit and vegetable consumption reduces the risk of cancerous and non-cancerous respiratory illnesses including non-smoking-related cancer incidence and deaths.
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http://dx.doi.org/10.1038/s41430-019-0393-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340537PMC
November 2019

Factors Associated With Outcomes of Patients With Primary Sclerosing Cholangitis and Development and Validation of a Risk Scoring System.

Hepatology 2019 05 4;69(5):2120-2135. Epub 2019 Mar 4.

Norfolk and Norwich University Hospital, Norwich, United Kingdom.

We sought to identify factors that are predictive of liver transplantation or death in patients with primary sclerosing cholangitis (PSC), and to develop and validate a contemporaneous risk score for use in a real-world clinical setting. Analyzing data from 1,001 patients recruited to the UK-PSC research cohort, we evaluated clinical variables for their association with 2-year and 10-year outcome through Cox-proportional hazards and C-statistic analyses. We generated risk scores for short-term and long-term outcome prediction, validating their use in two independent cohorts totaling 451 patients. Thirty-six percent of the derivation cohort were transplanted or died over a cumulative follow-up of 7,904 years. Serum alkaline phosphatase of at least 2.4 × upper limit of normal at 1 year after diagnosis was predictive of 10-year outcome (hazard ratio [HR] = 3.05; C = 0.63; median transplant-free survival 63 versus 108 months; P < 0.0001), as was the presence of extrahepatic biliary disease (HR = 1.45; P = 0.01). We developed two risk scoring systems based on age, values of bilirubin, alkaline phosphatase, albumin, platelets, presence of extrahepatic biliary disease, and variceal hemorrhage, which predicted 2-year and 10-year outcomes with good discrimination (C statistic = 0.81 and 0.80, respectively). Both UK-PSC risk scores were well-validated in our external cohort and outperformed the Mayo Clinic and aspartate aminotransferase-to-platelet ratio index (APRI) scores (C statistic = 0.75 and 0.63, respectively). Although heterozygosity for the previously validated human leukocyte antigen (HLA)-DR*03:01 risk allele predicted increased risk of adverse outcome (HR = 1.33; P = 0.001), its addition did not improve the predictive accuracy of the UK-PSC risk scores. Conclusion: Our analyses, based on a detailed clinical evaluation of a large representative cohort of participants with PSC, furthers our understanding of clinical risk markers and reports the development and validation of a real-world scoring system to identify those patients most likely to die or require liver transplantation.
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http://dx.doi.org/10.1002/hep.30479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6519245PMC
May 2019

Blood pressure differences between home monitoring and daytime ambulatory values and their reproducibility in treated hypertensive stroke and TIA patients.

Am Heart J 2019 01 19;207:58-65. Epub 2018 Oct 19.

Ageing and Stroke Medicine Section, Norwich Medical School, Bob Champion Research and Education Building, James Watson Rd, Norwich Research Park, University of East Anglia, Norwich, UK. Electronic address:

Background: Guidelines recommend ambulatory or home blood pressure monitoring to improve hypertension diagnosis and monitoring. Both these methods are ascribed the same threshold values, but whether they produce similar results has not been established in certain patient groups.

Methods: Adults with mild/moderate stroke or transient ischemic attack (N = 80) completed 2 sets of ambulatory and home blood pressure monitoring. Systolic and diastolic blood pressure values from contemporaneous measurements were compared, and the limits of agreement were assessed. Exploratory analyses for predictive factors of any difference were conducted.

Results: Daytime ambulatory blood pressure values were consistently lower than home values, the mean difference in systolic blood pressure for initial ambulatory versus first home monitoring was -6.6 ± 13.5 mm Hg (P≤.001), and final ambulatory versus second home monitoring was -7.1 ± 11.0mm Hg (P≤.001). Mean diastolic blood pressure differences were -2.1 ± 8.5mm Hg (P=.03) and -2.0 ± 7.2mm Hg (P=.02). Limits of agreement for systolic blood pressure were -33.0 to 19.9mm Hg and -28.7 to 14.5mm Hg for the 2 comparisons and for DBP were -18.8 to 14.5mm Hg and -16.1 to 12.2mm Hg, respectively. The individual mean change in systolic blood pressure difference was 11.0 ± 8.3mm Hg across the 2 comparisons. No predictive factors for these differences were identified.

Conclusions: Daytime ambulatory systolic and diastolic blood pressure values were significantly lower than home monitored values at both time points. Differences between the 2 methods were not reproducible for individuals. Using the same threshold value for both out-of-office measurement methods may not be appropriate in patients with cerebrovascular disease.
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http://dx.doi.org/10.1016/j.ahj.2018.09.005DOI Listing
January 2019

At-risk registers integrated into primary care to stop asthma crises in the UK (ARRISA-UK): study protocol for a pragmatic, cluster randomised trial with nested health economic and process evaluations.

Trials 2018 Aug 29;19(1):466. Epub 2018 Aug 29.

University of East Anglia, Norwich, UK.

Background: Despite effective treatments and long-standing management guidelines, there are approximately 1400 hospital admissions for asthma weekly in the United Kingdom (UK), many of which could be avoided. In our previous research, a secondary analysis of the intervention (ARRISA) suggested an improvement in the management of at-risk asthma patients in primary care. ARRISA involved identifying individuals at risk of adverse asthma events, flagging their electronic health records, training practice staff to develop and implement practice-wide processes of care when alerted by the flag, plus motivational reminders. We now seek to determine the effectiveness and cost-effectiveness of ARRISA in reducing asthma-related crisis events.

Methods: We are undertaking a pragmatic, two-arm, multicentre, cluster randomised controlled trial, plus health economic and process evaluation. We will randomise 270 primary care practices from throughout the UK covering over 10,000 registered patients with 'at-risk asthma' identified according to a validated algorithm. Staff in practices randomised to the intervention will complete two 45-min eLearning modules (an individually completed module giving background to ARRISA and a group-completed module to develop practice-wide pathways of care) plus a 30-min webinar with other practices. On completion of training at-risk patients' records will be coded so that a flag appears whenever their record is accessed. Practices will receive a phone call at 4 weeks and a reminder video at 6 weeks and 6 months. Control practices will continue to provide usual care. We will extract anonymised routine patient data from primary care records (with linkage to secondary care data) to determine the percentage of at-risk patients with an asthma-related crisis event (accident and emergency attendances, hospitalisations and deaths) after 12 months (primary outcome). We will also capture the time to crisis event, all-cause hospitalisations, asthma control and any changes in practice asthma management for at-risk and all patients with asthma. Cost-effectiveness analysis and mixed-methods process evaluations will also be conducted.

Discussion: This study is novel in terms of using a practice-wide intervention to target and engage with patients at risk from their asthma and is innovative in the use of routinely captured data with record linkage to obtain trial outcomes.

Trial Registration: ISRCTN95472706 . Registered on 5 December 2014.
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http://dx.doi.org/10.1186/s13063-018-2816-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6116486PMC
August 2018

Effect of Antiplatelet Therapy (Aspirin + Dipyridamole Versus Clopidogrel) on Mortality Outcome in Ischemic Stroke.

Am J Cardiol 2018 09 30;122(6):1085-1090. Epub 2018 Jul 30.

Institute of Applied Health Sciences, Aberdeen, United Kingdom.

The optimal regimen of antiplatelet therapy for secondary prevention in noncardioembolic ischemic stroke remains controversial. We aimed to determine which regimen was associated with the greatest reduction in adverse outcomes. We analysed prospectively collected data from the Norfolk and Norwich University Hospital Stroke Register. The sample population consisted of 3,572 participants (mean age 74.96 ± 12.67) with ischemic stroke, who were consecutively admitted between 2003 and 2015. Patients were placed on one of three antiplatelet regimens at hospital discharge; aspirin monotherapy, aspirin plus dipyridamole and clopidogrel. Clopidogrel and aspirin plus dipyridamole were compared to aspirin. A direct comparison between clopidogrel and aspirin plus dipyridamole was also performed. Outcomes included all-cause mortality and a combined end point of all-cause mortality and incidence of major adverse cardiac events (stroke or myocardial infarction). Cox-regression models adjusted for potential confounders at the following time periods after discharge; 0 to 90 days, 91 to 365 days, and 1 to 3 years. Aspirin plus dipyridamole was associated with a lower risk of mortality at 0 to 90 days; hazard ratio (HR) 0.62 (0.43 to 0.91). Clopidogrel was associated with a lower risk of mortality at 1 to 3 years; HR of 0.39 (0.26 to 0.60). Similar HRs were observed for the corresponding time points in the composite outcome. In conclusion, patients with noncardioembolic stroke may gain maximum benefits from aspirin plus dipyridamole initially (≤1 year) with a subsequent switch to clopidogrel, with regard to mortality and major adverse cardiac eventsoutcomes.
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http://dx.doi.org/10.1016/j.amjcard.2018.05.043DOI Listing
September 2018

Does self-monitoring and self-management of blood pressure after stroke or transient ischemic attack improve control? TEST-BP, a randomized controlled trial.

Am Heart J 2018 09 27;203:105-108. Epub 2018 Jul 27.

Ageing and Stroke Medicine Section, Norwich Medical School, University of East Anglia, Norwich, UK. Electronic address:

The therapeutic benefit of self-monitoring blood pressure in stroke patients is uncertain. We investigated the effect of self-monitoring with or without guided antihypertensive management compared with usual care in patients with a recent cerebrovascular event. No between-group differences in blood pressure at outcome were found, but blood pressure self-monitoring and management was well tolerated.
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http://dx.doi.org/10.1016/j.ahj.2018.06.002DOI Listing
September 2018

Long-Term Factors Associated With Falls and Fractures Poststroke.

Front Neurol 2018 3;9:210. Epub 2018 Apr 3.

Ageing Clinical and Experimental Research (ACER) Team, School of Medicine, Medical Sciences & Nutrition, Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, United Kingdom.

Background: Risk factors for poststroke falls and fractures remain poorly understood. This study aimed to evaluate which factors increased risk of these events after stroke.

Methods: Data from 7,267 hospitalized stroke patients were acquired from the Norfolk and Norwich University Hospital Stroke Register from 2003-2015. The impacts of multiple patient level and stroke characteristics and comorbidities on post-discharge falls and fractures were assessed. Univariate and multivariable models were constructed, adjusting for multiple confounders, using binary logistic regression for short-term analysis (up to 1-year post-discharge) and Cox-proportional hazard models for longer term analysis (1-3, 3-5, and 0-10 years follow-up).

Results: The mean age (SD) was 76.3 ± 12.1 years at baseline. 1,138 (15.7%) participants had an incident fall; and 666 (9.2%) an incident fracture during the 10-year follow-up (total person years = 64,447.99 for falls and 67,726.70 for fractures). Half of the sample population were females (50.6%) and the majority had an ischemic stroke (89.8%). After adjusting for confounders: age, sex, previous history of falls, and atrial fibrillation were associated with an increased risk of both falls and fractures during follow-up. Furthermore, chronic kidney disease and hyperlipidemia were associated with an increased risk of falls, while previous stroke/transient ischemic attack increased fracture risk. Total anterior circulation stroke and a prestroke modified Rankin Scale score of 3-5 were associated with decreased risk of both events, with hypertension and cancer decreasing risk of falls only.

Conclusion: We identified demographic, stroke-related, and comorbid factors associated with poststroke falls and fracture incidence. Further studies are required to examine and establish the relationship between reversible factors and further explore the role of preventative measures to prevent poststroke falls and fractures.
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http://dx.doi.org/10.3389/fneur.2018.00210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5891595PMC
April 2018

Baseline anticholinergic burden from medications predicts incident fatal and non-fatal stroke in the EPIC-Norfolk general population.

Int J Epidemiol 2018 04;47(2):625-633

Ageing Clinical & Experimental Research (ACER) Team, Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, UK.

Background: Stroke is primarily a disease of older age, with a substantial impact on global mortality and morbidity. Medications with anticholinergic effects are widely used, but no studies have been conducted to examine the relationship between anticholinergic burden (ACB) and stroke in a general population.

Method: The sample was drawn from the EPIC-Norfolk cohort. Baseline assessments were carried out during 1993-97 and participants were followed up until March 2016. Participants were divided into four groups according to their total ACB score at baseline; these groups were those with a total ACB score of 0, 1, 2-3 and >3. After exclusion, Cox proportional hazards models were constructed to determine the associations between the ACB score groups and the risk of incident stroke and stroke mortality. Sensitivity analysis and propensity score matched analyses were performed.

Results: In total 25 639 participants attended the first health check; 3917 participants were excluded, leaving 21 722 participants to be included. Participants had a mean age [standard deviation (SD)] of 58.9 (9.2) years (54.4% women). Of these, 2131 suffered incident stroke and 562 died from stroke. Mean follow-up was approximately 18 years for both outcomes. In the fully adjusted model, those with an ACB of >3 had 59% relative risk of incident stroke {hazard ratio [HR] [95% confidence interval (CI) 1.59 [1.34-1.89]} and 86% relative risk of stroke mortality [1.86 (1.37-2.53)] compared with those in ACB 0 category. Sensitivity analyses and propensity score matched analyses showed similar results.

Conclusions: Our results provide an incentive for the cautious use of medications with anticholinergic properties, to help reduce the global burden of stroke.
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http://dx.doi.org/10.1093/ije/dyx265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198932PMC
April 2018

The Efficacy and Mechanism Evaluation of Treating Idiopathic Pulmonary fibrosis with the Addition of Co-trimoxazole (EME-TIPAC): study protocol for a randomised controlled trial.

Trials 2018 Feb 5;19(1):89. Epub 2018 Feb 5.

University of East Anglia, Norwich, UK.

Background: We hypothesise, based upon the findings from our previous trial, that the addition of co-trimoxazole to standard therapy is beneficial to patients with moderate to severe idiopathic pulmonary fibrosis (IPF). We aim to investigate this by assessing unplanned hospitalisation-free survival (defined as time from randomisation to first non-elective hospitalisation, lung transplant or death) and to determine whether any effect relates to changes in infection and/or markers of disease control and neutrophil activity.

Methods/design: The EME-TIPAC trial is a double-blind, placebo-controlled, randomised, multicentre clinical trial. A total of 330 symptomatic patients, aged 40 years old or older, with IPF diagnosed by a multidisciplinary team (MDT) according to international guidelines and a FVC ≤ 75% predicted will be enrolled. Patients are randomised equally to receive either two tablets of co-trimoxazole 480 mg or two placebo tablets twice daily over a median treatment period of 27 (range 12-42) months. All patients receive folic acid 5 mg daily whilst on the trial IMP to reduce the risk of bone marrow depression. The primary outcome for the trial is a composite endpoint consisting of the time to death, transplant or first non-elective hospital admission and will be determined from adverse event reporting, hospital databases and the Office of National Statistics with active tracing of patients missing appointments. Secondary outcomes include the individual components of the primary outcome, (1) King's Brief Interstitial Lung Disease Questionnaire, (2) MRC Dyspnoea Score, (3) EQ5D, (4) spirometry, (5) total lung-diffusing capacity and (6) routine sputum microbiology. Blood will be taken for cell count, biochemistry and analysis of biomarkers including C-reactive protein and markers of disease. The trial will last for 4 years. Recruitment will take place in a network of approximately 40 sites throughout the UK (see Table 1 for a full list of participating sites). We expect recruitment for 30 months, follow-up for 12 months and trial analysis and reporting to take 4 months.

Discussion: The trial is designed to test the hypothesis that treating IPF patients with co-trimoxazole will increase the time to death (all causes), lung transplant or first non-elective hospital admission compared to standard care ( https://www.nice.org.uk/guidance/cg163 ), in patients with moderate to severe disease. The mechanistic aims are to investigate the effect on lung microbiota and other measures of infection, markers of epithelial injury and markers of neutrophil activity.

Trial Registration: International Standard Randomised Controlled Trials Number (ISRCTN) Registry, ID: 17464641 . Registered on 29 January 2015.
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http://dx.doi.org/10.1186/s13063-018-2453-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5800095PMC
February 2018

Impact of anaemia on acute stroke outcomes depends on the type of anaemia: Evidence from a UK stroke register.

J Neurol Sci 2017 Dec 30;383:26-30. Epub 2017 Sep 30.

Ageing Clinical and Experimental Research (ACER), Institute of Applied Health Sciences, School of Medicine, Medical Sciences & Nutrition, University of Aberdeen, Aberdeen, UK; Stroke Research Group, Norfolk and Norwich University Hospital, Norwich, UK; Norwich Medical School, University of East Anglia, Norwich, UK. Electronic address:

Background: Previous research has demonstrated an association between anaemia and poor outcomes in acute stroke. This study aimed to assess the impact of anaemia on stroke by anaemia subtype.

Methods: Data from a prospective UK Regional Stroke Register were used to assess the association between hypochromic microcytic and normochromic normocytic anaemia on inpatient-mortality, length of stay (LOS) and discharge modified Rankin scale (mRS). Analysis was stratified by stroke subtypes and multivariable logistic regression, adjusting for potential confounders, was used to quantify this association. Patients who were not anaemic were the reference category.

Results: A total of 8167 stroke patients (admitted between 2003 and 2015) were included, mean age (SD) 77.39±11.90years. Of these, 3.4% (n=281) had hypochromic microcytic anaemia and 15.5% (n=1262) had normochromic normocytic anaemia on admission. Normochromic normocytic anaemia was associated with increased odds of in-patient mortality OR 1.48 (1.24-1.77), 90-day mortality OR 1.63 (1.38-1.92), longer LOS OR 1.21 (1.06-1.40), defined as >7days, and severe disability defined as discharge mRS≥3 OR 1.31 (1.06-1.63), in patients with ischaemic stroke. Hypochromic microcytic anaemia was associated with 90-day mortality OR 1.90 (1.40-2.58) and a longer LOS OR 1.57 (1.20-2.05) in patients with ischaemic stroke.

Conclusions: Hypochromic microcytic and normochromic normocytic anaemia are associated with differing outcomes in terms of inpatient mortality and post stroke disability. While it is unclear if anaemia per se or another underlying cause is responsible for adverse outcomes, subtype of anaemia appears to be relevant in stroke prognosis.
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http://dx.doi.org/10.1016/j.jns.2017.09.047DOI Listing
December 2017