Publications by authors named "Thang S Han"

108 Publications

Predicting Stroke Complications in Hospital and Functional Status at Discharge by Clustering of Cardiovascular Diseases a Multi-Centre Registry-Based Study of Acute Stroke.

J Stroke Cerebrovasc Dis 2021 Oct 21;31(1):106162. Epub 2021 Oct 21.

Institute of Cardiovascular Research, Royal Holloway University of London, Egham, TW20 0EX, UK; Department of Clinical Neuroscience, Imperial College Healthcare NHS Trust, London W6 8RF, UK. Electronic address:

Objective: Indicators for outcomes following acute stroke are lacking. We have developed novel evidence-based criteria for identifying outcomes of acute stroke using the presence of clusters of coexisting cardiovascular disease (CVD).

Materials And Methods: Analysis of prospectively collected data from the Sentinel Stroke National Audit Programme (SSNAP). A total of 1656 men (mean age ±SD=73.1yrs±13.2) and 1653 women (79.3yrs±13.0) were admitted with acute stroke (83.3% ischaemic, 15.7% intracranial haemorrhagic), 1.0% unspecified) in four major UK hyperacute stroke units (HASU) between 2014 and 2016. Four categories from cardiovascular disease Congestive heart failure, Atrial fibrillation, pre-existing Stroke and Hypertension (CASH).were constructed: CASH-0 (no coexisting CVD); CASH-1 (any one coexisting CVD); CASH-2 (any two coexisting CVD); CASH-3 (any three or all four coexisting CVD). These were tested against outcomes, adjusted for age and sex.

Results: Compared to CASH-0, individuals with CASH-3 had greatest risks of in-hospital mortality (11.1% vs 24.5%, OR=1.8, 95%CI=1.3-2.7) and disability (modified Rankin Scale score ≥4) at discharge (24.2% vs 46.2%, OR=1.9, 95%CI=1.4-2.7), urinary tract infection (3.8% vs 14.6%, OR= 3.3, 95%CI= 1.9-5.5), and pneumonia (7.1% vs 20.6%, OR= 2.6, 95%CI= 1.7-4.0); length of stay on HASU >14 days (29.8% vs 39.3%, OR=1.8, 95%CI=1.3-2.6); and joint-care planning (20.9% vs 29.8%, OR=1.4, 95%CI=1.0-2.0).

Conclusions: We present a simple tool for estimating the risk of adverse outcomes of acute stroke including death, disability at discharge, nosocomial infections, prolonged length of stay, as well as any joint care planning. CASH-0 indicates a low level and CASH-3 indicates a high level of risk of such complications after stroke.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.106162DOI Listing
October 2021

Association of risk of malnutrition with adverse outcomes and early support on discharge in acute stroke patients without prestroke disability: A multicenter, registry-based cohort study.

Nutr Clin Pract 2021 Oct 19. Epub 2021 Oct 19.

Institute of Cardiovascular Research, Royal Holloway University of London, Egham, UK.

Background: Malnutrition in hospitals remains highly prevalent. As part of quality improvement initiatives, the Royal College of Physicians recommends nutrition screening for all patients admitted with acute stroke. We aimed to examine the associations of patients at risk of malnutrition with poststroke outcomes.

Methods: We analyzed prospectively collected data from four hyperacute stroke units (HASUs) (2014-2016). Nutrition status was screened in 2962 acute stroke patients without prestroke disability (1515 men, [mean ± SD] 73.5 years ± 13.1; 1447 women, 79.2 ± 13.0 years). The risk of malnutrition was tested against stroke outcomes and adjusted for age, sex, and comorbidities.

Results: Risk of malnutrition was identified in 25.8% of patients). Compared with well-nourished patients, those at risk of malnutrition had, within 7 days of admission, increased risk of stay on the HASU of >14 days (odds ratio [OR]: 9.9 [7.3-11.5]), disability on discharge (OR: 8.1 [6.6-10.0]), worst level of consciousness in the first 7 days (score ≥ 1) (OR: 7.5 [6.1-9.3]), mortality (OR: 5.2 [4.0-6.6], pneumonia (OR: 5.1 [3.9-6.7]), and urinary tract infection (OR: 1.5 [1.1-2.0]). They also required palliative care (OR: 12.3 [8.5-17.8]), discharge to new care home (OR: 3.07 [2.18-4.3]), activities of daily living support (OR: 1.8 [1.5-2.3]), planned joint care (OR: 1.5 [1.2-1.8]), and weekly visits (OR: 1.4 [1.1-1.8]).

Conclusion: Patients at risk of malnutrition more commonly have multiple adverse outcomes after acute stroke and greater need for early support on discharge.
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http://dx.doi.org/10.1002/ncp.10790DOI Listing
October 2021

Changes in Characteristics and Outcomes of Patients Undergoing Surgery for Hip Fractures Following the Initiation of Orthogeriatric Service: Temporal Trend Analysis.

Calcif Tissue Int 2021 Aug 27. Epub 2021 Aug 27.

Institute of Cardiovascular Research, Royal Holloway, University of London, Egham, TW20 0EX, Surrey, UK.

The Blue Book published by the British Orthopaedic Association and British Geriatrics Society, together with the introduction of National Hip Fracture Database Audit and Best Practice Tariff, have been influential in improving hip fracture care. We examined ten-year (2009-2019) changes in hip fracture outcomes after establishing an orthogeriatric service based on these initiatives, in 1081 men and 2891 women (mean age = 83.5 ± 9.1 years). Temporal trends in the annual percentage change (APC) of outcomes were identified using the Joinpoint Regression Program v4.7.0.0. The proportions of patients operated beyond 36 h of admission fell sharply during the first two years: APC =  - 53.7% (95% CI - 68.3, - 5.2, P = 0.003), followed by a small rise thereafter: APC = 5.8% (95% CI 0.5, 11.3, P = 0.036). Hip surgery increased progressively in patients > 90 years old: APC = 3.3 (95% CI 1.0, 5.8, P = 0.011) and those with American Society of Anaesthesiologists grade ≥ 3: APC = 12.4 (95% CI 8.8, 16.1, P < 0.001). There was a significant decline in pressure ulcers amongst patients < 90 years old: APC =  - 17.9 (95% CI - 32.7, 0.0, P = 0.050) and also a significant decline in mortality amongst those > 90 years old: APC =  - 7.1 (95% CI - 12.6, - 1.3, P = 0.024). Prolonged length of stay (> 23 days) declined from 2013: APC =  - 24.6% (95% CI - 31.2, - 17.4, P < 0.001). New discharge to nursing care declined moderately over 2009-2016 (APC =  - 10.6, 95% CI - 17.2, - 2.7, P = 0.017) and sharply thereafter (APC =  - 47.5%, 95%CI - 71.7, - 2.7, P = 0.043). The rate of patients returning home was decreasing (APC =  - 2.9, 95% CI - 5.1, - 0.7, P = 0.016), whilst new discharge to rehabilitation was increasing (APC = 8.4, 95% CI 4.0, 13.0; P = 0.002). In conclusion, the establishment of an orthogeriatric service was associated with a reduction of elapsed time to hip surgery, a progressive increase in surgery carried out on high-risk adults and a decline in adverse outcomes.
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http://dx.doi.org/10.1007/s00223-021-00906-4DOI Listing
August 2021

Changes in cortisol levels by continuous positive airway pressure in patients with obstructive sleep apnoea: Meta-analysis of 637 individuals.

Clin Endocrinol (Oxf) 2021 12 6;95(6):909-917. Epub 2021 Aug 6.

Institute of Cardiovascular Research, Royal Holloway, University of London, Surrey, UK.

Background: Obesity, obstructive sleep apnoea (OSA) and hypertension frequently coexist and are associated with elevated cortisol levels. Identification and treatment of such patients is important when investigating for suspected Cushing's syndrome and hypertension. Studies of the impact of continuous positive airway pressure (CPAP) on cortisol and blood pressure are limited by the small sample size and show conflicting findings. We conducted a meta-analysis to document changes in the levels of cortisol and blood pressure in response to CPAP treatment of OSA.

Methods: Meta-analysis was conducted using RevMan (v5.3) and expressed in standardized mean difference (SMD) for catecholamines and mean difference for systolic (SBP) and diastolic blood pressure (DBP). The quality of the studies was evaluated using standard tools for assessing the risk of bias.

Results: A total of 22 studies met our search criteria; they consisted of 16 prospective cohort studies (PCS) that recruited 385 participants and six randomized control trials (RCT) totalling 252 participants. The range of mean age was 41-62 years and BMI 27.2-35.1 kg/m . CPAP treatment reduced plasma cortisol levels in PCS: SMD = -0.28 [95% confidence interval (95% CI) = -0.45 to -0.12], I  = 0%, p = .79 and in RCT: SMD = -0.39 (95% CI = -0.75 to -0.03), I  = 28.3%, p = .25. CPAP treatment reduced SBP by 5.4 mmHg (95% CI = 1.7-9.1) and DBP by 3.3 mmHg (95% CI = 1.0-5.7). Interstudy heterogeneity was low for all studies. Bias in most RCT arose from the lack of blinding of participants and personnel.

Conclusion: CPAP treatment in individuals with OSA reduces cortisol levels and blood pressure.
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http://dx.doi.org/10.1111/cen.14573DOI Listing
December 2021

Adverse consequences of immediate thrombolysis-related complications: a multi-centre registry-based cohort study of acute stroke.

J Thromb Thrombolysis 2021 Jul 13. Epub 2021 Jul 13.

Institute of Cardiovascular Research, Royal Holloway University of London, Egham, TW20 0EX, UK.

Complications following thrombolysis for stroke are well documented, and mostly concentrated on haemorrhage. However, the consequences of patients who experience any immediate thrombolysis-related complications (TRC) compared to patients without immediate TRC have not been examined. Prospectively collected data from the Sentinel Stroke National Audit Programme were analysed. Thrombolysis was performed in 451 patients (52.1% men; 75.3 years ± 13.2) admitted with acute ischaemic stroke (AIS) in four UK centres between 2014 and 2016. Adverse consequences following immediate TRC were assessed using logistic regression, adjusted for age, sex and co-morbidities. Twenty-nine patients (6.4%) acquired immediate TRC. Compared to patients without, individuals with immediate TRC had greater adjusted risks of: moderately-severe or severe stroke (National Institutes of Health for Stroke Scale score ≥ 16) at 24-h (5.7% vs 24.7%, OR 3.9, 95% CI 1.4-11.1); worst level of consciousness (LOC) in the first 7 days (score ≥ 1; 25.0 vs 60.7, OR 4.6, 95% CI 2.1-10.2); urinary tract infection or pneumonia within 7-days of admission (13.5% vs 39.3%, OR 3.2, 95% CI 1.3-7.7); length of stay (LOS) on hyperacute stroke unit (HASU) ≥ 2 weeks (34.7% vs 66.7%, OR 5.2, 95% CI 1.5-18.4); mortality (13.0% vs 41.4%, OR 3.7, 95% CI 1.6-8.4); moderately-severe or severe disability (modified Rankin Scale  score ≥ 4) at discharge (26.8% vs 65.5%, OR 4.7, 95% CI 2.1-10.9); palliative care by discharge date (5.1% vs 24.1%, OR 5.1, 95% CI 1.7-15.7). The median LOS on the HASU was longer (7 days vs 30 days, Kruskal-Wallis test: χ = 8.9, p = 0.003) while stroke severity did not improve (NIHSS score at 24-h post-thrombolysis minus NIHSS score at arrival = - 4 vs 0, χ = 24.3, p < 0.001). In conclusion, the risk of nosocomial infections, worsening of stroke severity, longer HASU stay, disability and death is increased following immediate TRC. The management of patients following immediate TRC is more complex than previously thought and such complexity needs to be considered when planning an increased thrombolysis service.
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http://dx.doi.org/10.1007/s11239-021-02523-2DOI Listing
July 2021

Continuous positive airway pressure therapy reduces the levels of catecholamines and blood pressure in pseudophaeochromocytoma with coexisting obstructive sleep apnoea.

JRSM Cardiovasc Dis 2021 Jan-Dec;10:2048004021992191. Epub 2021 Mar 17.

Institute of Cardiovascular Research, Royal Holloway, University of London, Egham, Surrey, UK.

Background: Stress from obstructive sleep apnoea (OSA) stimulates catecholamine release and consequently can exacerbate hypertension, even in the absence of a catecholamine-producing tumour (phaeochromocytoma). As such, a positive screening test for suspected phaeochromocytoma may be misleading. There exists only a handful case reports, and no controlled trials, how continuous positive airway pressure (CPAP) to treat OSA influences catecholamine levels. We examined changes to levels of urinary catecholamine and blood pressure in response to CPAP treatment.

Methods: We conducted a meta-analysis of data aggregated from published case reports of individual patient data up to April 2020. The quality of the reports was evaluated using the risk of bias in non-randomized studies of interventions (ROBINS-I) tool.

Results: A total of 13 cases (seven men and six women) from seven reports met our search criteria. Patients had mean age of 49.1 years (range = 36-62) and body mass index of 37.4 kg/m (range = 27-56). Most had moderate to severe OSA with CPAP treatment. Nine cases had 24-hour urinary noradrenaline assessment before and after CPAP treatment. CPAP treatment led to a 21% reduction (104 nmol/24-hours, 95% credible interval =59 to 148) in 24-hour urinary noradrenaline to within reference ranges, and 25% reduction (from 131 to 100 mmHg) in mean arterial pressure. The risk of overall bias evaluated by the ROBINS-I tool was found to be low in the majority of reports.

Conclusions: Investigations of patients suspected of phaeochromocytoma, particularly obese individuals, should exclude OSA and treat this condition if present before performing screening tests to assess for catecholamine levels.
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http://dx.doi.org/10.1177/2048004021992191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217809PMC
March 2021

The smoking-dyslipidaemia dyad: A potent synergistic risk for atherosclerotic coronary artery disease.

JRSM Cardiovasc Dis 2021 Jan-Dec;10:2048004020980945. Epub 2021 Mar 15.

Institute of Cardiovascular Research, Royal Holloway University of London, Egham, UK.

Background: Smoking and dyslipidaemia are known individual risk factors of coronary artery disease (CAD). The present study examined the combined risk of smoking and dyslipidaemia on coronary atherosclerosis.

Methods: Coronary artery calcium (CAC), measured by cardiac CT, was used to assess the extent of CAD, which was related to smoking and dyslipidaemia using logistic regression, adjusted for age, sex, hypertension, BMI and family history of ischaemic heart disease.

Results: Seventy-one patients (46 men, 25 women: median age of 53.7yrs; IQR = 47.0-59.5) were recruited. The mean log CAC score in never-smokers without dyslipidaemia (reference group) was 0.37 (SD = 0.73), while the value in those with a history of smoking was 0.44 ± 0.48 (mean difference: 0.07, 95%CI:-0.67 to 0.81,  = 0.844), dyslipidaemia was 1.07 ± 1.08 (mean difference: 0.71, 95%CI: 0.24 to 1.17,  = 0.003), and both risk factors was 1.82 ± 0.64 (mean difference: 1.45, 95%CI:0.88 to 2.02,  < 0.001). For individuals in the reference group, the proportions with none, one and multiple vessel disease were 80.6%, 16.1% and 3.2%; for those with a history of smoking or with dyslipidaemia were 50.0%, 25.0% and 25.0%; and for those with both risk factors were 8.3%, 25.0% and 66.7%. Patients with a history of both risk factors had greater adjusted risks of having one- vessel disease - OR = 14.3 (95%CI = 2.1-98.2) or multiple vessel disease: OR = 51.8 (95%CI = 4.2-609.6).

Conclusions: Smoking and dyslipidaemia together are associated with high coronary artery calcification and CAD, independent of other major risk factors.
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http://dx.doi.org/10.1177/2048004020980945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968041PMC
March 2021

Prediction of Paroxysmal Atrial Fibrillation From Complexity Analysis of the Sinus Rhythm ECG: A Retrospective Case/Control Pilot Study.

Front Physiol 2021 19;12:570705. Epub 2021 Feb 19.

Department of Biochemical Sciences, Faculty of Health and Medical Sciences, School of Biosciences and Medicine, University of Surrey, Surrey, United Kingdom.

Paroxysmal atrial fibrillation (PAF) is the most common cardiac arrhythmia, conveying a stroke risk comparable to persistent AF. It poses a significant diagnostic challenge given its intermittency and potential brevity, and absence of symptoms in most patients. This pilot study introduces a novel biomarker for early PAF detection, based upon analysis of sinus rhythm ECG waveform complexity. Sinus rhythm ECG recordings were made from 52 patients with ( = 28) or without ( = 24) a subsequent diagnosis of PAF. Subjects used a handheld ECG monitor to record 28-second periods, twice-daily for at least 3 weeks. Two independent ECG complexity indices were calculated using a Lempel-Ziv algorithm: R-wave interval variability (beat detection, BD) and complexity of the entire ECG waveform (threshold crossing, TC). TC, but not BD, complexity scores were significantly greater in PAF patients, but TC complexity alone did not identify satisfactorily individual PAF cases. However, a composite complexity score (-score) based on within-patient BD and TC variability scores was devised. The -score allowed correct identification of PAF patients with 85% sensitivity and 83% specificity. This powerful but simple approach to identify PAF sufferers from analysis of brief periods of sinus-rhythm ECGs using hand-held monitors should enable easy and low-cost screening for PAF with the potential to reduce stroke occurrence.
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http://dx.doi.org/10.3389/fphys.2021.570705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933455PMC
February 2021

Validity of the LACE index for identifying frequent early readmissions after hospital discharge in children.

Eur J Pediatr 2021 May 15;180(5):1571-1579. Epub 2021 Jan 15.

School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, BS8 1TD, UK.

The LACE index scoring tool has been designed to predict hospital readmissions in adults. We aimed to evaluate the ability of the LACE index to identify children at risk of frequent readmissions. We analysed data from alive-discharge episodes (1 April 2017 to 31 March 2019) for 6546 males and 5875 females from birth to 18 years. The LACE index predicted frequent all-cause readmissions within 28 days of hospital discharge with high accuracy: the area under the curve = 86.9% (95% confidence interval = 84.3-89.5%, p < 0.001). Two-graph receiver operating characteristic curve analysis revealed the LACE index cutoff to be 4.3, where sensitivity equals specificity, to predict frequent readmissions. Compared with those with a LACE index score = 0-4 (event rates, 0.3%), those with a score > 4 (event rates, 3.7%) were at increased risk of frequent readmissions: age- and sex-adjusted odds ratio = 12.4 (95% confidence interval = 8.0-19.2, p < 0.001) and death within 30 days of discharge: OR = 5.0 (95% CI = 1.5-16.7). The ORs for frequent readmissions were between 6 and 14 for children of different age categories (neonate, infant, young child and adolescent), except for patients in the child category (6-12 years) where odds ratio was 2.8.Conclusion: The LACE index can be used in healthcare services to identify children at risk of frequent readmissions. Focus should be directed at individuals with a LACE index score above 4 to help reduce risk of readmissions. What is Known: • The LACE index scoring tool has been widely used to predict hospital readmissions in adults. What is New: • Compared with children with a LACE index score of 0-4 (event rates, 0.3%), those with a score > 4 are at increased risk of frequent readmissions by 14-fold. • The cutoff of a LACE index of 4 may be a useful level to identify children at increased risk of frequent readmissions.
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http://dx.doi.org/10.1007/s00431-021-03929-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032568PMC
May 2021

Increased Association With Malnutrition and Malnourishment in Older Adults Admitted With Hip Fractures Who Have Cognitive Impairment and Delirium, as Assessed by 4AT.

Nutr Clin Pract 2021 Oct 23;36(5):1053-1058. Epub 2020 Dec 23.

School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, UK.

Background: The Royal College of Physicians recently introduced the 4AT (Alertness, Abbreviated Mental Test-4, Attention, and Acute change or fluctuating course) for screening cognitive impairment and delirium. Here, we examined the association of the 4AT with nutrition status in patients admitted to a hospital with hip fractures between January 1, 2016, and June 6, 2019.

Methods: Nutrition status was assessed using the Malnutrition Universal Screening Tool, and the 4AT was assessed within 1 day after hip surgery. χ Tests and logistic regression were conducted to assess the association of nutrition status with 4AT scores, adjusted for age and sex.

Results: From 1082 patients aged 60-103 years, categorized into 4AT scores of 0, 1-3, or ≥4, the prevalence of malnutrition risk was 15.5%, 27.3%, and 39.6% and malnourishment was 4.1%, 13.2%, and 11.3%, respectively. Compared with the 4AT = 0 cohort, a 4AT score = 1-3 was associated with an increased malnutrition risk (odds ratio [OR], 2.3; 95% CI, 1.6-3.1) or malnourishment (OR, 3.6; 95% CI, 2.1-6.3). For a 4AT score ≥4, corresponding ORs were 4.0 (95% CI, 2.8-5.9) and 3.6 (95% CI, 1.9-6.8). Overall, there was a significant positive association: as 4AT scores increased, so did malnutrition risk.

Conclusions: Among older adults admitted with hip fractures, high 4AT scores, which are suggestive of cognitive impairment and delirium, identified patients at increased malnutrition risk. These findings lend further support for the use of 4AT to identify patients who are at increased health risk.
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http://dx.doi.org/10.1002/ncp.10614DOI Listing
October 2021

Prevalence and consequences of malnutrition and malnourishment in older individuals admitted to hospital with a hip fracture.

Eur J Clin Nutr 2021 04 7;75(4):645-652. Epub 2020 Oct 7.

School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, BS8 1TD, UK.

Background/objectives: Major causes of hip fractures are osteoporosis and falls, both of which are determined by nutrition. Information on the nutritional status of patients admitted to hospital with a hip fracture is lacking. In this study, we assessed determinants and adverse outcomes associated with malnutrition and malnourishment.

Methods: Nutritional status, assessed using the Malnutrition Universal Screening Tool protocol, was compared to age and residency prior to admission, and outcomes during hospital stay and at discharge.

Results: A total of 1239 patients admitted with a hip fracture (349 men, 890 women), aged 60-100 years. Compared with well-nourished individuals, the prevalences of malnutrition risk or malnourishment were higher in older age groups and those from residential or nursing care. Those with risk of malnutrition or malnourishment stayed in hospital longer by 3.0 days (95% confidence interval (CI), 1.5-4.5 days; p < 0.001) and 3.1 days (95% CI, 0.7-5.5 days; p = 0.011), respectively. Compared with the well-nourished group, malnourished individuals had increased: (1) risk for failure to mobilise within 1 day of surgery (rates = 17.9 versus 27.0%; odds ratio (OR) = 1.6 (95% CI, 1.0-2.7), p = 0.045); (2) pressure ulcers (rates = 1.0% versus 5.0%; OR = 5.5 (95% CI, 1.8-17.1), p = 0.006); (3) in-patient mortality (rates = 4.5% versus 10.1%; OR = 2.3 (95% CI, 1.1-4.8) p = 0.033) and (4) discharge to residential/nursing care: rates = 4.3% versus 11.1%; OR = 2.8 (95% CI, 1.2-6.6), p = 0.022.

Conclusions: Inadequate nutrition is common in patients admitted to hospital with a hip fracture, which in turn predisposes them to a number of complications. More research on nutritional support should be directed to this group to prevent or minimise hip fractures.
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http://dx.doi.org/10.1038/s41430-020-00774-5DOI Listing
April 2021

Meta-analysis of changes in the levels of catecholamines and blood pressure with continuous positive airway pressure therapy in obstructive sleep apnea.

J Clin Hypertens (Greenwich) 2021 01 24;23(1):12-20. Epub 2020 Sep 24.

Institute of Cardiovascular Research, Royal Holloway, University of London, Egham, UK.

Stress from obstructive sleep apnea (OSA) stimulates catecholamine release consequently exacerbating hypertension. However, different studies have shown a conflicting impact of continuous positive airway pressure (CPAP) treatment in patients with OSA on catecholamine levels and blood pressure. We aimed to examine changes to catecholamine levels and blood pressure in response to CPAP treatment. We conducted a meta-analysis of data published up to May 2020. The quality of the studies was evaluated using standard tools for assessing the risk of bias. Meta-analysis was conducted using RevMan (v5.3) and expressed in standardized mean difference (SMD) for catecholamines and mean difference (MD) for systolic (SBP) and diastolic blood pressure (DBP). A total of 38 studies met our search criteria; they consisted of 14 randomized control trials (RCT) totaling 576 participants and 24 prospective cohort studies (PCS) of 547 participants. Mean age ranged between 41 and 62 year and body mass index between 27.2 and 35.1 kg/m . CPAP treatment reduced 24-hour urinary noradrenaline levels both in RCT (SMD = -1.1; 95% confidence interval (CI): -1.63 to - 0.56) and in PCS (SMD = 0.38 (CI: 0.24 to 0.53). SBP was also reduced by CPAP treatment in RCT (4.8 mmHg; CI: 2.0-7.7) and in PCS (7.5 mmHg; CI: 3.3-11.7). DBP was similarly reduced (3.0 mmHg; CI: 1.4-4.6) and in PCS (5.1 mmHg; CI: 2.3-8.0). In conclusion, CPAP treatment in patients with OSA reduces catecholamine levels and blood pressure. This suggests that sympathetic activity plays an intermediary role in hypertension associated with OSA-related stress.
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http://dx.doi.org/10.1111/jch.14061DOI Listing
January 2021

The Ability of the Nottingham Hip Fracture Score to Predict Mobility, Length of Stay and Mortality in Hospital, and Discharge Destination in Patients Admitted with a Hip Fracture.

Calcif Tissue Int 2020 10 11;107(4):319-326. Epub 2020 Jul 11.

Institute of Cardiovascular Research, Royal Holloway, University of London, Egham, Surrey, TW20 0EX, UK.

The Nottingham Hip Fracture Score (NHFS) has been developed for predicting 30-day and 1-year mortality after hip fracture. We hypothesise that NHFS may also predict other adverse events. Data from 666 patients (190 men, 476 women), aged 60.2-103.4 years, admitted with a hip fracture to a single centre from 1/10/2015 and 7/12/2017 were analysed. The ability of NHFS to predict mobility within 1 day after surgery, length of stay (LOS) find mortality, and discharge destination was evaluated by receiver operating characteristic curves and two-graph plots. The area under the curve (95% confidence interval [CI]) for predicting mortality was 67.4% (58.4-76.4%), prolonged LOS was 59.0% (54.0-64.0%), discharge to residential/nursing care was 62.3% (54.0-71.5%), and any two of failure to mobilise, prolonged LOS or discharge to residential/nursing care was 64.8% (59.0-70.6%). NHFS thresholds at 4 and 7 corresponding to the lower and upper limits of intermediate range where sensitivity and specificity equal 90% were identified for mortality and prolonged LOS, and 4 and 6 for discharge to residential/nursing care, which were used to create three risk categories. Compared with the low risk group (NHFS = 0-4), the high risk group (NHFS = 7-10 or 6-10) had increased risk of in-patient mortality: rates = 2.0% versus 7.1%, OR (95% CI) = 3.8 (1.5-9.9), failure to mobilise within 1 day of surgery: rates = 18.9% versus 28.3%, OR = 1.7 (1.0-2.8), prolonged LOS (> 17 days): rates = 20.3% versus 33.9%, OR = 2.2 (1.3-3.3), discharge to residential/nursing care: rates = 4.5% vs 12.3%, OR = 3.0 (1.4-6.4), and any two of failure to mobilise, prolonged LOS or discharge to residential/nursing care: rates = 10.5% versus 28.6%, 3.4 (95% CI 1.9-6.0), and stayed 4.1 days (1.5-6.7 days) longer in hospital. High NHFS associates with increased risk of mortality, prolonged LOS and discharge to residential/nursing care, lending further support for its use to identify adverse events.
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http://dx.doi.org/10.1007/s00223-020-00722-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7497295PMC
October 2020

LACE index predicts age-specific unplanned readmissions and mortality after hospital discharge.

Aging Clin Exp Res 2021 Apr 5;33(4):1041-1048. Epub 2020 Jun 5.

Department of Endocrinology, Ashford and St Peter's Hospitals NHS Foundation Trust, Guildford Road, Chertsey, KT16 0PZ, Surrey, UK.

Background: The LACE index scoring tool (Length of stay, Acuity of admission, Co-morbidities and Emergency department visits) has been designed to predict hospital readmissions. We evaluated the ability of the LACE index to predict age-specific frequent admissions and mortality.

Methods: Analysis of prospectively collected data of alive-discharge episodes between 01/04/2017 and 31/03/2019 in an NHS hospital. Data on 14,878 men and 17,392 women of mean age 64.0 years, SD = 20.5, range 18.0-106.7 years were analysed. The association of the LACE index with frequency of all-cause readmissions within 28 days of discharge and over a 2-year period, and with all-cause mortality within 30 days or within 6 months after discharge from hospital were evaluated.

Results: Within LACE index scores of 0-4, 5-9 or ≥ 10, the proportions of readmission ≥ 2 times within 28 days of discharge were 0.1, 1.3 and 9.2% (χ = 3070, p < 0.001) and over a 2-year period were 1.7, 4.8 and 19.1% (χ = 3364, p < 0.001). Compared with a LACE index score of 0-4, a score ≥ 10 increased the risk (adjusted for age, sex and frequency of admissions) of death within 6 months of discharge by 6.8-fold (5.1-9.0, p < 0.001) among all ages, and most strongly in youngest individuals (18.0-49.9 years): adjusted odds ratio = 16.1 (5.7-45.8, p < 0.001). For those aged 50-59.9, 60-69.9, 70-79.9 and ≥ 80 years, odds ratios reduced progressively to 9.6, 7.7, 5.1 and 2.3, respectively. Similar patterns were observed for the association of LACE index with mortality within 30 days of hospital discharge.

Conclusions: The LACE index predicts short-term and long-term frequent admissions and short-term and medium-term mortality, most pronounced among younger individuals, after hospital discharge.
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http://dx.doi.org/10.1007/s40520-020-01609-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084827PMC
April 2021

Response by Han and Sharma to Letter Regarding Article, "Prestroke Disability Predicts Adverse Poststroke Outcome: A Registry-Based Prospective Cohort Study of Acute Stroke".

Stroke 2020 06 13;51(6):e117. Epub 2020 May 13.

Department of Clinical Neuroscience, Imperial College Healthcare NHS Trust, London, United Kingdom.

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http://dx.doi.org/10.1161/STROKEAHA.120.029952DOI Listing
June 2020

Changing trends in the use of novel oral anticoagulants and warfarin for treating non-valvular atrial fibrillation.

JRSM Cardiovasc Dis 2020 Jan-Dec;9:2048004020915406. Epub 2020 Mar 29.

Institute of Cardiovascular Research, Royal Holloway, University of London, Egham, UK.

Background: Prevention of thromboembolism by novel oral anticoagulants is increasing, whilst use of vitamin K antagonists is on the decline. We assessed changes in the use of these anticoagulants in treating non-valvular atrial fibrillation between 2014 and 2018.

Methods: One-hundred and sixty-two consecutive patients (95 men, 67 women) with non-valvular atrial fibrillation, mean age 72.3 years (standard deviation = 11.0), underwent cardiac assessment in a single cardiac unit. Use of anticoagulants at the time of investigation was documented: overall 83 (51.2%) patients were prescribed novel oral anticoagulants and 79 (48.8%) warfarin treatment. Trends in treatment rates with either anticoagulant class over time were characterised by calculating the average annual percentage change using a Joinpoint Regression Program 4.7.0.0.

Results: There were diverging trends in anticoagulant treatment from 2014 to 2018 without join points: yearly increase in novel oral anticoagulant treatment (41.9, 45.5, 53.7, 53.1 and 72.7%, average annual percentage change = 16.2%, 95% confidence interval = 5.8% to 27.5%,  < 0.001), and decrease in warfarin treatment (57.1, 54.5, 46.3, 46.9 and 27.3%, average annual percentage change = -14.4%, 95% confidence interval = -25.2% to -2.1%,  < 0.001).

Conclusions: Changing trends in treatment with anticoagulants for patients with non-valvular atrial fibrillation observed within less than two years provide important information to healthcare services to estimate future pharmaco-economic costs for such treatments.
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http://dx.doi.org/10.1177/2048004020915406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7119231PMC
March 2020

Sex differences in the agreement between left ventricular ejection fraction measured by myocardial perfusion scintigraphy and by echocardiography.

JRSM Cardiovasc Dis 2020 Jan-Dec;9:2048004020915393. Epub 2020 Mar 24.

Institute of Cardiovascular Research, Royal Holloway, University of London, Egham, UK.

Background: Left ventricular ejection fraction (LVEF) is generally measured by echocardiography but is increasingly available with myocardial perfusion scintigraphy. With myocardial perfusion scintigraphy, the threshold of LVEF below which there is a risk for myocardial infarct or sudden cardiac death is higher for women (51%) than for men (43%). We tested the hypothesis that such a sex difference may also occur with echocardiography and myocardial perfusion scintigraphy.

Methods: Four hundred and four men, mean age = 67.7 ± SD = 12.3 yr; 339 women, 67.7 ± 11.7 yr had separate myocardial perfusion scintigraphy and echocardiography examinations within six months. A subset of 327 of these patients (181 men, 68.8 ± 12.1 yr; 146 women, 66.4 ± 12.1 yr) had examinations within one month and were additionally analysed as this sub-group. Myocardial perfusion scintigraphy and echocardiography were used to measure LVEF at rest and their agreement (neither considered as a reference method) was assessed by Bland-Altman plots: LVEF difference (myocardial perfusion scintigraphy minus echocardiography ) against average LVEF ( ).

Results: Of patients who had myocardial perfusion scintigraphy and echocardiography performed within six months, mean LVEF difference = +1.1% (95% limits of agreement: -19.3 to +21.6) in men but +10.9% (-10.7 to +32.5) in women. LVEF difference diverged from zero marginally in men (mean difference = +1.1, 95%CI  = +0.1 to +2.1,  =  0.028) but more in women (+10.9, +9.8 to +12.1,  < 0.001). The LVEF difference correlated with average LVEF itself in both men ( =  0.305,  < 0.001) and women ( =  0.361,  < 0.001), and with age in women ( = 0.117,  = 0.031). Similar results were observed for the subset.

Conclusions: Caution should be taken when interpreting LVEF measured by different techniques due to their wide limits of agreement and systematic bias, more markedly in women.
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http://dx.doi.org/10.1177/2048004020915393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093695PMC
March 2020

Correction to: The role of virtual reality on outcomes in rehabilitation of Parkinson's disease: meta-analysis and systematic review in 1031 participants.

Neurol Sci 2020 Mar;41(3):731-732

Institute of Cardiovascular Research Royal Holloway, University of London, Egham, Surrey, TW20 0EX, UK.

The originally published version of this article contained typesetting errors in Figure 4.
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http://dx.doi.org/10.1007/s10072-019-04212-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645488PMC
March 2020

Prestroke Disability Predicts Adverse Poststroke Outcome: A Registry-Based Prospective Cohort Study of Acute Stroke.

Stroke 2020 02 17;51(2):594-600. Epub 2019 Dec 17.

From the Institute of Cardiovascular Research, Royal Holloway University of London, Egham, United Kingdom (T.S.H., S.S., P.S.).

Background and Purpose- Information on what effect disability before stroke can have on stroke outcome is lacking. We assessed prestroke disability in relation to poststroke hospital outcome. Methods- Analysis of prospectively collected data from the Sentinel Stroke National Audit Programme. A total of 1656 men (mean age ±SD =73.1±13.2 years) and 1653 women (79.3±13.0 years) were admitted to hyperacute stroke units with acute stroke in 4 major UK between 2014 and 2016. Prestroke disability, assessed by modified Rankin Scale (mRS), was tested against poststroke adverse outcomes, adjusted for age, sex, and coexisting morbidities. Results- Compared with patients with prestroke mRS score =0, individuals with prestroke mRS scores =3, 4, or 5 had greater adjusted risks of moderately severe or severe stroke on arrival (4.4% versus 16.7%; odds ratio [OR], 3.2 [95% CI, 2.3-4.6] <0.001); urinary tract infection or pneumonia within 7 days of admission (9.6% versus 35.9%; OR, 3.7 [95% CI, 2.8-4.8] <0.001); mortality (7.2% versus 37.1%; OR, 4.9 [95% CI, 3.7-6.5] <0.001); requiring help with activities of daily living on discharge (12.3% versus 26.7%; OR, 3.1 [95% CI, 2.3-4.1] <0.001); and transferred to new care home (2.4% versus 9.4%; OR, 2.1 [95% CI, 1.3-3.3] =0.002). Patients with mRS scores =1 or 2 had intermediate risk of adverse outcomes. Overall, those with a mRS score =1 or 2 had length of stay on hyperacute stroke units extended by 5.3 days (95% CI, 2.8-7.7; <0.001) and mRS score =3, 4 or 5 by 7.2 days (95% CI, 4.0-10.5; <0.001). Conclusions- Individuals with evidence of prestroke disability, assessed by mRS, had significantly increased risk of poststroke adverse outcomes and longer length of stay on hyperacute stroke units and higher level of care on discharge.
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http://dx.doi.org/10.1161/STROKEAHA.119.027740DOI Listing
February 2020

Associations of 4AT with mobility, length of stay and mortality in hospital and discharge destination among patients admitted with hip fractures.

Age Ageing 2020 04;49(3):411-417

Institute of Cardiovascular Research, Royal Holloway, University of London, Surrey TW20 0EX, UK.

Background: the 4AT (Alertness, Abbreviated Mental Test-4, Attention and Acute change or fluctuating course), a tool to screen cognitive impairment and delirium, has recently been recommended by the Scottish Intercollegiate Guidelines Network. We examined its ability to predict health outcomes among patients admitted with hip fractures to a single hospital between January 2018 and June 2019.

Methods: the 4AT was performed within 1 day after hip surgery. A 4AT score of 0 means unlikely delirium or severe cognitive impairment (reference group); a score of 1-3 suggests possible chronic cognitive impairment, without excluding possibility of delirium; a score ≥ 4 suggests delirium with or without chronic cognitive impairment. Logistic regression, adjusted for: age; sex; nutritional status; co-morbidities; polypharmacy; and anticholinergic burden, used the 4AT to predict mobility, length of stay (LOS), mortality and discharge destination, compared with the reference group.

Results: from 537 (392 women, 145 men: mean = 83.7 ± standard deviation [SD] = 8.8 years) consecutive patients, 522 completed the 4AT; 132 (25%) had prolonged LOS (>2 weeks) and 36 (6.8%) died in hospital. Risk of failure to mobilise within 1 day of surgery was increased with a 4AT score ≥ 4 (OR = 2.4, 95% confidence interval [CI] = 1.3-4.3). Prolonged LOS was increased with 4AT scores of 1-3 (OR = 2.4, 95%CI = 1.4-4.1) or ≥4 (OR = 3.1, 95%CI = 1.9-6.7). In-patient mortality was increased with a 4AT score ≥ 4 (OR = 3.1, 95%CI = 1.2-8.2) but not with a 4AT score of 1-3. Change of residence on discharge was increased with a 4AT score ≥ 4 (OR = 3.1, 95%CI = 1.4-6.8). These associations persisted after excluding patients with dementia. 4AT score = 1-3 and ≥ 4 associated with increased LOS by 3 and 6 days, respectively.

Conclusions: for older adults with hip fracture, the 4AT independently predicts immobility, prolonged LOS, death in hospital and change in residence on discharge.
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http://dx.doi.org/10.1093/ageing/afz161DOI Listing
April 2020

The role of virtual reality on outcomes in rehabilitation of Parkinson's disease: meta-analysis and systematic review in 1031 participants.

Neurol Sci 2020 Mar 6;41(3):529-536. Epub 2019 Dec 6.

Institute of Cardiovascular Research Royal Holloway, University of London, Egham, Surrey, TW20 0EX, UK.

Introduction: Parkinson's disease (PD) is managed primarily by dopamine agonists and physiotherapy while virtual reality (VR) has emerged recently as a complementary method. The present study reviewed the effectiveness of VR in rehabilitation of patients with PD.

Methods: Literature search up to June 2019 identified ten studies (n = 343 participants) suitable for meta-analysis and 27 studies (n = 688 participants) for systematic review. Standard mean difference (SMD) and 95% confidence intervals (CI) were calculated using a random effects model.

Results: In meta-analysis, compared with active rehabilitation intervention, VR training led to greater improvement of stride length, SMD = 0.70 (95%CI = 0.32-1.08, p = 0.0003), and was as effective for gait speed, balance and co-ordination, cognitive function and mental health, quality of life and activities of daily living. Compared with passive rehabilitation intervention, VR had greater effects on balance: SMD = 1.02 (95%CI = 0.38-1.65, p = 0.002). Results from single randomised controlled trials showed that VR training was better than passive rehabilitation intervention for improving gait speed SMD = 1.43 (95%CI = 0.51-2.34, p = 0.002), stride length SMD = 1.27 (95%CI = 0.38-2.16, p = 0.005) and activities of daily living SMD = 0.96 (95%CI = 0.02-1.89). Systematic review showed that VR training significantly (p < 0.05) improved motor function, balance and co-ordination, cognitive function and mental health, and quality of life and activities of daily living.

Conclusion: VR used in rehabilitation for patients with PD improves a number of outcomes and may be considered for routine use in rehabilitation.
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http://dx.doi.org/10.1007/s10072-019-04144-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7040061PMC
March 2020

Life Expectancy of White and Non-White Elite Heavyweight Boxers.

J Racial Ethn Health Disparities 2020 04 3;7(2):281-289. Epub 2019 Dec 3.

Human Nutrition, School of Medicine, University of Glasgow, Glasgow, UK.

Background: In post-industrial countries, ethnic minorities suffer poorer health and premature deaths. The present study examined ethnic differences in life expectancy and related features among elite heavyweight boxers.

Methods: Dates of birth and death, anthropometry, and championship years were gathered from media archives for champions and challengers (never been a champion) between years 1889 and 2019. Cox regression adjusted for age at contest, nationality, BMI, champion/challenger status, and number of contests was used to assess survival.

Results: All 237 boxers, 83 champions (37.3% whites) and 154 challengers (61.0% whites), who contested for heavyweight championships were identified. By 2019, 110 (75 whites, 34 non-whites) were known to have died. Non-white boxers died at an earlier age than whites boxers (mean ± SD = 59.8 ± 14.2 years versus 67.3 ± 16.4 years, p = 0.018) and had shorter survival: HR = 2.13 (95% CI = 1.4-3.3). Among non-white boxers, deaths were higher from neurological disorders: OR = 8.2 (95% CI = 1.3-13.5) and accidents: OR = 15.1 (95% CI = 2.3-98.2), while death from natural causes was lower: OR = 0.2 (95% CI = 0.03-0.8). After boxing careers, fewer non-white boxers had non-manual jobs (34.4% versus 71.8%) than manual (34.4% versus 19.7%) or were unemployed (28.1% versus 2.8%). Reported substance abuse was similar across ethnicity (8.0% versus 8.8%) but conviction rates were higher among non-white boxers (17.6%) than white (1.3%).

Conclusions: Compared with white boxers, non-white boxers tend to die younger with excess neurological and accidental deaths, and they have lower social positions in later life. Sporting authorities should reappraise the wisdom of permitting head injuries in sport and monitor and support the health and wellbeing of sports men and women after retirement.
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http://dx.doi.org/10.1007/s40615-019-00656-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7064515PMC
April 2020

A clinical perspective of parathyroid hormone related hypercalcaemia.

Rev Endocr Metab Disord 2020 03;21(1):77-88

Institute of Cardiovascular Research, Royal Holloway, University of London, Egham, UK.

There are many causes of hypercalcaemia including hyperparathyroidism, drugs, granulomatous disorders and malignancy. Parathyroid hormone (PTH) related hypercalcaemia is most commonly caused by primary hyperparathyroidism (PHPT) and more rarely by familial hypocalciuric hypercalcaemia (FHH). Algorithms for diagnosis of PTH related hypercalcaemia require assessment of a 24-h urinary calcium and creatinine excretion to calculate calcium/creatinine clearance ratio and radiological investigations including ultrasound scan and Tc-sestamibi-SPECT/CT. To illustrate investigations and management of parathyroid-related hypercalcaemia, we present a selection of distinct cases of PHPT due to eutopic and ectopic parathyroid adenomas, as well as a case with a syndromic form of PHPT (multiple endocrine neoplasia type 1), and a case with FHH type 1 due to a CASR inactivating mutation. Additional cases with normocalcaemic hyperparathyroidism and secondary hyperparathyroidism are included for completeness of differential diagnosis. The common eutopic parathyroid adenomas are easily treated with parathyroidectomy while the less common ectopic parathyroid adenomas require more complex investigations and operative procedures such as video-assisted thoracoscopic surgery. On the other hand, the much less common FHH does not require treatment. Assessment of kin with FHH is important to identify members with this inherited condition in order to prevent unnecessary interventions.
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http://dx.doi.org/10.1007/s11154-019-09529-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113199PMC
March 2020

Current status of stroke in Qatar: Including data from the BRAINS study.

JRSM Cardiovasc Dis 2019 Jan-Dec;8:2048004019869160. Epub 2019 Aug 18.

Institute of Cardiovascular Research, Royal Holloway University of London , London, UK.

Background: Qatar is located on the north-eastern coast of the Arabian Peninsula. Qatari natives account for less than 15% of the population while the largest migrant group comprising 60% derives from South Asia. Despite projections that stroke burden in Qatar will increase with population ageing, epidemiological studies focusing on stroke in Qatar are relatively scarce.

Method: We reviewed the available epidemiological publications relating to Qatar. In addition, we have added to this knowledge by incorporating Qatari data from the on-going Bio-Repository of DNA in Stroke, an independent multinational database of stroke patients.

Results: Qatar has low reported incidence and mortality rates of 58 and 9.17 per 100,000 per year, respectively, which may be explained by its middle-aged migrant worker majority population. Correspondingly, South Asian migrants in Qatar suffered younger strokes than Qatari natives (48.7 vs 63.4 years, P < 0.001). Among the most common risk factors identified in stroke patients were hypertension (77.9%), diabetes (43.8%) and hypercholesterolemia (28.5%). Ischaemic stroke was the most frequent subtype amongst migrant South Asians (71.1%). The majority of stroke cases had computed tomography and/or magnetic resonance imaging scans, but only 11.1% of ischaemic strokes were thrombolysed. Qataris on one-year follow up were more often found to have died (6.5% vs 0.3%) and had further stroke/transient ischaemic attack events (17.4% vs 6.4%, P = 0.009) compared to South Asians.

Conclusion: The burden of stroke is increasing in Qatar, and considerable disparities are observed between the native and migrant populations which likely will require different approaches to management by its healthcare system.
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http://dx.doi.org/10.1177/2048004019869160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700866PMC
August 2019

Prothrombin Complex Concentrates are Superior to Fresh Frozen Plasma for Emergency Reversal of Vitamin K Antagonists: A Meta-Analysis in 2606 Subjects.

Drugs 2019 Sep;79(14):1557-1565

Department of Medicine, Imperial College London, Imperial College Healthcare NHS Trust, London, SW7 2AZ, UK.

Background: Urgent reversal of vitamin K antagonists (VKAs) is required for major bleeding or urgent surgery by intravenous vitamin K with either prothrombin complex concentrates (PCCs) or fresh frozen plasma (FFP). However, there is lack of consensus regarding the superiority of either reversal agent. We sought to compare the performance of PCC and FFP in urgent reversal of VKA.

Methods: A meta-analysis was conducted up to November 2018. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random effects model.

Results: Seventeen studies comprising 2606 participants met the inclusion criteria. Compared with FFP treatment, PCC treatment led to a reduction in 90-day all-cause mortality (OR 0.60, 95% CI 0.40-0.90, p = 0.01), better reversal of INR (OR 7.36, 95% CI 4.18-12.98; p < 0.00001) and lower risk of at least one treatment-related adverse event (OR 0.45, 95% CI 0.26-0.80, p = 0.006). Among patients with VKA-associated intracranial haemorrhage, PCC treatment led to a reduction in 90-day all-cause mortality (OR 0.58, 95% CI 0.35-0.94, p = 0.03) and better reversal of INR (OR 6.52, 95% CI 1.66-25.59, p = 0.007). There were no differences between these two agents in thrombogenicity, requirement for and quantity of red blood cell transfusions, all adverse events, fluid overload or disability on discharge or at 90 days.

Conclusions: As an agent for urgent reversal of VKA, PCC outperforms FFP in 90-day all-cause mortality including those with VKA-related intracranial haemorrhage, INR reversal and treatment-related adverse events.
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http://dx.doi.org/10.1007/s40265-019-01179-wDOI Listing
September 2019

Influences of genetic variants on stroke recovery: a meta-analysis of the 31,895 cases.

Neurol Sci 2019 Dec 29;40(12):2437-2445. Epub 2019 Jul 29.

Institute of Cardiovascular Research Royal Holloway, University of London, Egham, Surrey, TW20 0EX, UK.

Background: The influences of genetic variants on functional clinical outcomes following stroke are unclear. In order to reliably quantify these influences, we undertook a comprehensive meta-analysis of outcomes after acute intracerebral haemorrhage (ICH) or ischaemic stroke (AIS) in relation to different genetic variants.

Methods: PubMed, PsycInfo, Embase and Medline electronic databases were searched up to January 2019. Outcomes, defined as favourable or poor, were assessed by validated scales (Barthel index, modified Rankin scale, Glasgow outcome scale and National Institutes of Health stroke scale).

Results: Ninety-two publications comprising 31,895 cases met our inclusion criteria. Poor outcome was observed in patients with ICH who possessed the APOE4 allele: OR =2.60 (95% CI = 1.25-5.41, p = 0.01) and in AIS patients with the GA or AA variant at the BDNF-196 locus: OR = 2.60 (95% CI = 1.25-5.41, p = 0.01) or a loss of function allele of CYP2C19: OR = 2.36 (95% CI = 1.56-3.55, p < 0.0001). Poor outcome was not associated with APOE4: OR = 1.02 (95% CI = 0.81-1.27, p = 0.90) or IL6-174 G/C: OR = 2.21 (95% CI = 0.55-8.86, p = 0.26) in patients with AIS.

Conclusions: We demonstrate that recovery of AIS was unfavourably associated with variants of BDNF and CYP2C19 genes whilst recovery of ICH was unfavourably associated with APOE4 gene.
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http://dx.doi.org/10.1007/s10072-019-04024-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6848040PMC
December 2019

Utility of surgeon-performed pre-operative ultrasound in the localisation of parathyroid adenomas.

JRSM Cardiovasc Dis 2019 Jan-Dec;8:2048004019856950. Epub 2019 Jun 19.

Department of Endocrinology, Ashford & St Peter's NHS Foundation Trust, Chertsey, UK.

Background: Primary hyperparathyroidism arising from parathyroid adenoma is one of the most common endocrine disorders treated by endocrine surgeons. The adenoma is commonly identified by imaging techniques. The present study evaluated the performance of a portable ultrasound machine (Sonosite MicroMaxx) operated by a surgeon, departmental ultrasound and Tc-sestamibi-SPECT/CT by a radiologist in the identification of parathyroid adenomas.

Methods: Patient case notes were retrieved from medical records and imaging from picture archiving and communication system over the period from 2006 to 2012. Tc-sestamibi-SPECT/CT and departmental ultrasound images were reported by a nuclear radiologist. The ability of each imaging technique in localising parathyroid adenomas was referenced against the actual adenomas identified from parathyroidectomy.

Results: With reference to the actual site of the lesion, surgeon-performed ultrasound accurately localised the site of the lesion in 30/33 (90.1%) of cases with a sensitivity of 86.7%, departmental ultrasound accurately localised the site of the lesion in 21/26 (80.1%) of cases with a sensitivity of 79.2%. In 6/75 patients where Tc-sestamibi-SPECT/CT did not localise the lesion, departmental ultrasound did not localise any lesions correctly, while surgeon-performed ultrasound successfully located the adenoma in three (50%) of these six patients. Patients whose parathyroid adenomas identified by the surgeon were more likely to have shorter length of stay in hospital: odds ratio = 0.53 (95% confidence interval = 0.30-0.92, p = 0.025).

Conclusions: Surgeon-performed ultrasound for immediately pre-operative localisation improves identification of parathyroid adenomas and reduces length of stay in hospital, lending support for the use of this technique by endocrine surgeons.
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http://dx.doi.org/10.1177/2048004019856949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6585239PMC
June 2019

New evidence-based A1, A2, A3 alarm time zones for transferring thrombolysed patients to hyper-acute stroke units: faster is better.

Neurol Sci 2019 Aug 27;40(8):1659-1665. Epub 2019 Apr 27.

Institute of Cardiovascular Research, Royal Holloway, University of London, TW20 0EX, Egham, UK.

Objectives: The National Institute of Health and Clinical Excellence and The Royal College of Physicians recommend transferring thrombolysed patients with stroke to a hyperacute stroke unit (HASU) within 4 h from hospital arrival (T), but there is paucity of evidence to support this cut-off. We assessed if a shorter interval within this target threshold conferred a significant improvement in patient mortality.

Design: We conducted a retrospective analysis of prospectively collected data from the Sentinel Stroke National Audit Programme.

Setting: Four major UK hyperacute stroke centres between 2014 and 2016.

Participants: A total of 183 men (median age = 75 years, IQR = 66-83) and 169 women (median age = 81 years, IQR = 72.5-88) admitted with acute ischaemic stroke.

Main Outcome Measures: We evaluated T in relation to inpatient mortality, adjusted for age, sex, co-morbidities, stroke severity, time between procedures, time and day on arrival.

Results: There were 51 (14.5%) inpatient deaths. On ROC analysis, the AUC (area under the curve) was 61.1% (52.9-69.4%, p = 0.01) and the cut-off of T where sensitivity equalled specificity was 2 h/15 min (intermediate range = 30 min to 3 h/15 min) for predicting mortality. On logistic regression, compared with the fastest T group within 2 h/15 min, the slowest T group beyond upper limit of intermediate range (≥ 3 h/15 min) had an increased risk of mortality: 5.6% vs. 19.6%, adjusted OR = 5.6 (95%CI:1.5-20.6, p = 0.010).

Conclusions: We propose three new alarm time zones (A1, A2 and A3) to improve stroke survival: "A1 Zone" (T < 2 h/15 min) indicates that a desirable target, "A2 Zone" (T = 2 h/15 min to 3 h/15 min), indicates increasing risk and should not delay any further, and "A3 Zone" (T ≥ 3 h/15 min) indicates high risk and should be avoided.
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http://dx.doi.org/10.1007/s10072-019-03901-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6647361PMC
August 2019

Design and development of the Hypoglycaemia Symptom Rating Questionnaire (HypoSRQ).

Diabetes Res Clin Pract 2019 May 5;151:187-197. Epub 2019 Apr 5.

Health Psychology Research Unit, Orchard Building, Royal Holloway, University of London, Egham, Surrey TW20 0EX, UK; Health Psychology Research Ltd., Orchard Building, Royal Holloway, University of London, Egham, Surrey TW20 0EX, UK. Electronic address:

Aims: To evaluate the Hypoglycaemia Symptom Rating Questionnaire (HypoSRQ©) and relationships between self-reported hypoglycaemia and hypoglycaemia measured using blinded continuous glucose monitoring (CGM).

Methods: Diabetes outpatients (n = 113) recruited from Ashford and St. Peter's Hospital completed the HypoSRQ (recent weeks version) and provided clinical information. Thirty participants used blinded CGM for six days and completed the HypoSRQ (24-hour version) for seven days, at the end of each week (7-day version), and after four weeks (recent weeks version).

Results: The HypoSRQ had a single-factor structure and excellent internal consistency (α = 0.90). There was high correspondence in recalled symptoms, bother ratings and hypoglycaemic episodes across one week and four weeks (r = 0.84-0.98, p < 0.001). HypoSRQ-reported hypoglycaemia correlated significantly with CGM-measured hypoglycaemia (interstitial glucose ≤ 3.9 mmol/l) frequency (r = 0.72, p < 0.001) across six days. The magnitude of the correlation increased when the person's own threshold for detecting hypoglycaemia was used (r = 0.78, p < 0.001). The number of days (out of six) a person reported symptoms of hypoglycaemia was associated with the number of days CGM detected hypoglycaemia (interstitial glucose ≤ 3.9 mmol/l) (r = 0.83, p < 0.001) and remained significant after controlling for covariates.

Conclusions: Psychometric properties of the HypoSRQ make it attractive for use in people with insulin-treated diabetes. The HypoSRQ may be a less-invasive and more-economical alternative to CGM.
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http://dx.doi.org/10.1016/j.diabres.2019.04.010DOI Listing
May 2019

Associations of body fat and skeletal muscle with hypertension.

J Clin Hypertens (Greenwich) 2019 02 7;21(2):230-238. Epub 2018 Dec 7.

Human Nutrition, School of Medicine, University of Glasgow, Glasgow, UK.

Hypertension is known to be associated with obesity, while its relationship to skeletal muscle, SM (SM; a marker of general health and body function), remains uncertain. We analyzed population-based data of 22 591 men (mean age: 51.6 ± 16.9 years) and 27 845 nonpregnant women (50.6 ± 16.9 years) from Scottish Health Surveys (2003, 2008-2011) and Health Surveys for England (2003-2006, 2008-2013) including 2595 non-insulin- and 536 insulin-treated diabetic patients. Compared with normotensive individuals (no hypertension history with normal systolic [SBP < 140 mm Hg] and diastolic blood pressure [DBP < 90 mm Hg]), percent body fat (BF%) was significantly higher and percent SM lower (P < 0.001) in undetected (no hypertension history with raised SBP ≥ 140 and/or DBP ≥ 90 mm Hg), controlled (hypertension history with normal BP), uncontrolled (hypertension history with raised BP), and untreated hypertension. The prevalences of hypertension within BF% quintiles were 11.8%, 24.8%, 41.4%, 56.8%, and 71.6% and SM% quintiles were 67.5%, 53.3%, 39.5%, 27.4%, and 18.5%. Compared to referent groups (lowest BF% quintile or highest SM% quintile), odds ratio (age, sex, smoking, ethnicity, country, survey year, and diabetes adjusted) for having all types of hypertension in the highest BF% quintile was 5.5 (95% confidence interval = 5.0-5.9) and lowest SM% quintile was 2.3 (2.2-2.5). Compared with those without diabetes, individuals with diabetes had a 2.3-fold-2.6-fold greater risk of hypertension, independent of confounding factors and BF% or SM%. The associations of hypertension with BF% were higher than those with body mass index (BMI). In conclusion, both BF and SM should be considered when analyzing results from health surveys, rather than relying on BMI which does not discriminate between the two.
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http://dx.doi.org/10.1111/jch.13456DOI Listing
February 2019
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