Publications by authors named "Phyo K Myint"

178 Publications

The role of C-reactive protein as a prognostic marker in COVID-19.

Int J Epidemiol 2021 Mar 3. Epub 2021 Mar 3.

Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.

Background: C-reactive protein (CRP) is a non-specific acute phase reactant elevated in infection or inflammation. Higher levels indicate more severe infection and have been used as an indicator of COVID-19 disease severity. However, the evidence for CRP as a prognostic marker is yet to be determined. The aim of this study is to examine the CRP response in patients hospitalized with COVID-19 and to determine the utility of CRP on admission for predicting inpatient mortality.

Methods: Data were collected between 27 February and 10 June 2020, incorporating two cohorts: the COPE (COVID-19 in Older People) study of 1564 adult patients with a diagnosis of COVID-19 admitted to 11 hospital sites (test cohort) and a later validation cohort of 271 patients. Admission CRP was investigated, and finite mixture models were fit to assess the likely underlying distribution. Further, different prognostic thresholds of CRP were analysed in a time-to-mortality Cox regression to determine a cut-off. Bootstrapping was used to compare model performance [Harrell's C statistic and Akaike information criterion (AIC)].

Results: The test and validation cohort distribution of CRP was not affected by age, and mixture models indicated a bimodal distribution. A threshold cut-off of CRP ≥40 mg/L performed well to predict mortality (and performed similarly to treating CRP as a linear variable).

Conclusions: The distributional characteristics of CRP indicated an optimal cut-off of ≥40 mg/L was associated with mortality. This threshold may assist clinicians in using CRP as an early trigger for enhanced observation, treatment decisions and advanced care planning.
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http://dx.doi.org/10.1093/ije/dyab012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989395PMC
March 2021

Sex Differences in Ischemic Stroke Outcomes in Patients With Pulmonary Hypertension.

J Am Heart Assoc 2021 Mar 8;10(6):e019341. Epub 2021 Mar 8.

Keele Cardiovascular Research Group Centre for Prognosis Research Institute for Primary Care and Health Sciences Keele University Stoke-on-Trent UK.

Background The association between systemic hypertension and cerebrovascular disease is well documented. However, the impact of pulmonary hypertension (PH) on acute ischemic stroke outcomes is unknown despite PH being recognized as a risk factor for acute ischemic stroke. We aimed to determine the association between PH and adverse in-hospital outcomes after acute ischemic stroke, as well as whether there are sex differences in this association. Methods and Results Acute ischemic stroke admissions from the US National Inpatient Sample between October 2015 and December 2017 were included. The relationship between PH and outcomes (mortality, prolonged hospitalization >4 days, and routine home discharge) was analyzed using logistic regressions adjusting for demographics, comorbidities, and revascularization therapies. Interaction terms between PH and sex and age groups were also included. A total of 221 249 records representative of 1 106 045 admissions were included; 2.9% of patients had co-morbid PH, and 35.34% of those were male. PH was not associated with in-hospital mortality (odds ratio [OR], 0.96; 95% CI, 0.86-1.09) but was associated with increased odds of prolonged hospitalization (OR, 1.15; 95% CI, 1.09-1.22) and decreased odds of routine discharge (OR, 0.87; 95% CI, 0.81-0.94) for both sexes. Older patients with PH were significantly less likely to be discharged routinely (=0.028) than their younger counterparts. Compared with female patients with PH, men were 31% more likely to die in hospital (=0.024). Conclusions PH was not significantly associated with in-hospital mortality but was associated with prolonged hospitalization and adverse discharge status. Male patients with PH were more likely to die in hospital than female patients.
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http://dx.doi.org/10.1161/JAHA.120.019341DOI Listing
March 2021

Routine use of immunosuppressants is associated with mortality in hospitalised patients with COVID-19.

Ther Adv Drug Saf 2021 18;12:2042098620985690. Epub 2021 Feb 18.

Department of Geriatric Medicine, 3rd Floor Academic Centre, Llandough Hospital, Penlan Road, Penarth, CF64 2XX.

Background: Whilst there is literature on the impact of SARS viruses in the severely immunosuppressed, less is known about the link between routine immunosuppressant use and outcome in COVID-19. Consequently, guidelines on their use vary depending on specific patient populations.

Methods: The study population was drawn from the COPE Study (COVID-19 in Older People), a multicentre observational cohort study, across the UK and Italy. Data were collected between 27 February and 28 April 2020 by trained data-collectors and included all unselected consecutive admissions with COVID-19. Load (name/number of medications) and dosage of immunosuppressant were collected along with other covariate data. Primary outcome was time-to-mortality from the date of admission (or) date of diagnosis, if diagnosis was five or more days after admission. Secondary outcomes were Day-14 mortality and time-to-discharge. Data were analysed with mixed-effects, Cox proportional hazards and logistic regression models using non-users of immunosuppressants as the reference group.

Results: In total 1184 patients were eligible for inclusion. The median (IQR) age was 74 (62-83), 676 (57%) were male, and 299 (25.3%) died in hospital (total person follow-up 15,540 days). Most patients exhibited at least one comorbidity, and 113 (~10%) were on immunosuppressants. Any immunosuppressant use was associated with increased mortality: aHR 1.87, 95% CI: 1.30, 2.69 (time to mortality) and aOR 1.71, 95% CI: 1.01-2.88 (14-day mortality). There also appeared to be a dose-response relationship.

Conclusion: Despite possible indication bias, until further evidence emerges we recommend adhering to public health measures, a low threshold to seek medical advice and close monitoring of symptoms in those who take immunosuppressants routinely regardless of their indication. However, it should be noted that the inability to control for the underlying condition requiring immunosuppressants is a major limitation, and hence caution should be exercised in interpretation of the results.

Plain Language Summary: We do not have much information on how the COVID-19 virus affects patients who use immunosuppressants, drugs which inhibit or reduce the activity of the immune system. There are various conflicting views on whether immune-suppressing drugs are beneficial or detrimental in patients with the disease. This study collected data from 10 hospitals in the UK and one in Italy between February and April 2020 in order to identify any association between the regular use of immunosuppressant medicines and survival in patients who were admitted to hospital with COVID-19. 1184 patients were included in the study, and 10% of them were using immunosuppressants. Any immunosuppressant use was associated with increased risk of death, and the risk appeared to increase if the dose of the medicine was higher. We therefore recommend that patients who take immunosuppressant medicines routinely should carefully adhere to social distancing measures, and seek medical attention early during the COVID-19 pandemic.
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http://dx.doi.org/10.1177/2042098620985690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897811PMC
February 2021

Bioelectrical Impedance Versus Biochemical Analysis of Hydration Status: Predictive Value for Prolonged Hospitalisation and Poor Discharge Destination for Older Patients.

Healthcare (Basel) 2021 Feb 3;9(2). Epub 2021 Feb 3.

Ageing Clinical & Experimental Research Team, Institute of Applied Health Sciences, University of Aberdeen, Aberdeen AB24 3FX, UK.

Dehydration is prevalent in hospitalised patients and is associated with increased morbidity and mortality, particularly among the elderly (≥65 years). We aimed at comparing the performance of intracellular water to extracellular water ratio (ICW/ECW), calculated through a bioelectrical impedance analysis (BIA) of blood urea nitrogen, with the creatinine ratio (BUN/Cr) to predict poor outcomes in a cohort of prospectively identified patients. Data were combined from a cohort of elderly patients (≥65 years) admitted to hospital with fragility fracture ( = 125) and older adults aged ≥50 years admitted to hospital with stroke ( = 40). The association between hydration status and study outcomes (unfavourable discharge destination (rehabilitation, another ward, or death) and prolonged hospitalisation (>10 days)) was examined using logistic regression. The overall diagnostic accuracy of each hydration status measurement was assessed using the area under the receiver operating characteristic (ROC) curve. In 165 participants (mean age (SD) of 76.7 (9.2) years), an ICW/ECW ratio below the 25th percentile was associated with increased odds of poor discharge destination (OR (95% CI) = 4.25 (1.59-11.34)). Neither the relationship between the BUN/Cr ratio and prolonged stay nor discharge destination was significant. A BIA could be used utilised in conjunction with biochemical measurements to inform patient prognosis.
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http://dx.doi.org/10.3390/healthcare9020154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913174PMC
February 2021

Country-level determinants of the severity of the first global wave of the COVID-19 pandemic: an ecological study.

BMJ Open 2021 02 3;11(2):e042034. Epub 2021 Feb 3.

Institute of Applied Health Sciences, School of Medicine, Medical Sciences & Nutrition, University of Aberdeen, Aberdeen, UK.

Objective: We aimed to identify the country-level determinants of the severity of the first wave of the COVID-19 pandemic.

Design: Ecological study of publicly available data. Countries reporting >25 COVID-19 related deaths until 8 June 2020 were included. The outcome was log mean mortality rate from COVID-19, an estimate of the country-level daily increase in reported deaths during the ascending phase of the epidemic curve. Potential determinants assessed were most recently published demographic parameters (population and population density, percentage population living in urban areas, population >65 years, average body mass index and smoking prevalence); economic parameters (gross domestic product per capita); environmental parameters (pollution levels and mean temperature (January-May); comorbidities (prevalence of diabetes, hypertension and cancer); health system parameters (WHO Health Index and hospital beds per 10 000 population); international arrivals; the stringency index, as a measure of country-level response to COVID-19; BCG vaccination coverage; UV radiation exposure; and testing capacity. Multivariable linear regression was used to analyse the data.

Primary Outcome: Country-level mean mortality rate: the mean slope of the COVID-19 mortality curve during its ascending phase.

Participants: Thirty-seven countries were included: Algeria, Argentina, Austria, Belgium, Brazil, Canada, Chile, Colombia, the Dominican Republic, Ecuador, Egypt, Finland, France, Germany, Hungary, India, Indonesia, Ireland, Italy, Japan, Mexico, the Netherlands, Peru, the Philippines, Poland, Portugal, Romania, the Russian Federation, Saudi Arabia, South Africa, Spain, Sweden, Switzerland, Turkey, Ukraine, the UK and the USA.

Results: Of all country-level determinants included in the multivariable model, total number of international arrivals (beta 0.033 (95% CI 0.012 to 0.054)) and BCG vaccination coverage (-0.018 (95% CI -0.034 to -0.002)), were significantly associated with the natural logarithm of the mean death rate.

Conclusions: International travel was directly associated with the mortality slope and thus potentially the spread of COVID-19. Very early restrictions on international travel should be considered to control COVID-19 outbreaks and prevent related deaths.
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http://dx.doi.org/10.1136/bmjopen-2020-042034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868125PMC
February 2021

An ecological approach to the development of an active aging measurement in urban areas (AAMU).

BMC Public Health 2021 Jan 3;21(1). Epub 2021 Jan 3.

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

Background: An essential element in the process of "aging well" is the concept of Active Aging (AA). To propose an operational definition of Active Aging, the present study seeks to develop a new measurement tool through an ecological approach. The aim is to recognize significant indicators that play a role in assessing AA in urban areas.

Methods: This study was conducted through a two-phase process of consensus-building: 1) identifying a set of indicators that were likely candidates for inclusion based on literature review, and 2) a two-round modified Delphi survey using an international panel of academic experts in environmental sciences and gerontology to achieve consensus on the importance of the extracted indicators and validate the items. The panelists were asked to complete a researcher-developed questionnaire with an 11-point Likert scale based on the indicators derived in phase 1. Finally, the Delphi survey's valid indicators and criteria were utilized to develop the measurement tool.

Results: At the outset, a list of 111 indicators of AA was prepared through the desk study. A panel of 22 experts reviewed the extracted items and arrived at a consensus on 99 items in the first round and finalised in the second round. Thematic analysis of the panelists' open-ended responses revealed new concepts that would be explicitly considered by the consensus group. This developed measurement scale consists of five domains, i.e., individual, spatial, socio-economic, governance, and health-related, which contain 15 criteria and 99 indicators.

Conclusions: The present researchers have developed the active aging measure for urban settlements (AAMU), which can be used both by policy-makers and as an informal self-reported statement among the elderly. AAM's results in the elderly's residential environmental communities can improve policy-making to address urban design to sustain an active, healthy life among older people in urban environments.
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http://dx.doi.org/10.1186/s12889-020-10036-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778809PMC
January 2021

Long-term effects of gestational diabetes on bone mineral density and fracture risk: Analysis of the Norfolk cohort of the European Prospective Investigation into Cancer (EPIC-Norfolk) population-based study.

Maturitas 2021 Feb 18;144:68-73. Epub 2020 Nov 18.

School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, Scotland, UK. Electronic address:

Objectives: Gestational diabetes mellitus (GDM) is a common pregnancy complication. This study aims to investigate the association between a history of GDM and bone mineral density (BMD), fractures, and falls in later life.

Study Design: We used data from the Norfolk cohort of the European Prospective Investigation into Cancer (EPIC-Norfolk) where BMD at calcaneum was measured at second health check (1997-2000) using broadband ultrasound attenuation (BUA) and velocity of sound (VOS) in 7,515 women. Fractures and falls were documented from hospital admissions data via linkage with ENCORE (East Norfolk Commission Record) and history of GDM from health questionnaires at baseline. We examined the relationship between GDM and BUA/VOS using linear regression. Cox regression was used to estimate hazard ratios (HRs) for incident fractures and falls, controlling for age, BMI, smoking status, physical activity, area deprivation, self-reported stroke, use of diuretics, calcium and vitamin D supplements, social class and education, statin and total blood cholesterol, prevalent diabetes, hormone therapy and menopausal status.

Results: History of GDM (n = 183) was not statistically significantly associated with BUA/VOS in fully adjusted linear regression models with unstandardised beta coefficients (standard error): -0.37 (1.40) and -5.41 (3.48). GDM was significantly (p < 0.05) associated with risk of hip and all fractures, fully adjusted HRs(95 %CI) 2.46(1.54-3.92) and 1.60(1.09-2.35), respectively. Median follow-up from first live birth to date of admission was 53 and 52 years, respectively.

Conclusion: There was an association between history of GDM and risk of any fracture as well as hip fracture specifically. Further research is required to confirm this.
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http://dx.doi.org/10.1016/j.maturitas.2020.11.005DOI Listing
February 2021

Trial of Dexamethasone for Chronic Subdural Hematoma.

N Engl J Med 2020 12 16;383(27):2616-2627. Epub 2020 Dec 16.

From the Divisions of Neurosurgery (P.J.H., E.E., E.P.T., S. Tarantino, K.C., H.M., T.S., C.T., A.G.K.) and Neurology (E.A.W.), Department of Clinical Neurosciences, and the Division of Experimental Medicine and Immunotherapeutics (I.W.), Addenbrooke's Hospital, University of Cambridge, and the Cambridge Clinical Trials Unit, Cambridge University Hospitals NHS Foundation Trust (A.A., B.P., C.D.-W., I.W., S.B.), Cambridge, the Faculty of Health: Medicine, Dentistry and Human Sciences, University of Plymouth (E.E.), and the South West Neurosurgical Centre, Derriford Hospital (E.E., P.C.W., M.G.), Plymouth, Wessex Neurological Unit, University Hospital Southampton, Southampton (D.B., A.Z., P.H.), the Department of Neurosurgery, Queen Elizabeth University Hospital, Glasgow (N.S., K.A.), the Department of Neurosurgery, Leeds General Infirmary, Leeds (S. Thomson, I.A.A.), the Department of Neurosurgery, Royal Hallamshire Hospital, Sheffield (Y.Z.A.-T., D.H.), Translational Neurosurgery, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh (P.M.B.), Norwich Medical School, Faculty of Medicine and Health Sciences, University of East Anglia, Norwich (G.B.), the Department of Neurosurgery, Great Ormond Street Hospital and Institute of Child Health, University College London (A.C.), and the National Hospital for Neurology and Neurosurgery (H.J.M.), London, the Department of Neurosurgery, Manchester Centre for Clinical Neurosciences, Salford Royal Hospital, Manchester Academic Health Science Centre, Manchester (A.T.K.), the National Institute for Health Research Surgical Reconstruction and Microbiology Research Centre and Institute of Inflammation and Ageing, University of Birmingham, Birmingham (A.B.), and the Ageing Clinical and Experimental Research Group, Institute of Applied Health Sciences, University of Aberdeen, Aberdeen (P.K.M.) - all in the United Kingdom; and the Department of Neurology, Karolinska University Hospital, Stockholm (E.P.T.).

Background: Chronic subdural hematoma is a common neurologic disorder that is especially prevalent among older people. The effect of dexamethasone on outcomes in patients with chronic subdural hematoma has not been well studied.

Methods: We conducted a multicenter, randomized trial in the United Kingdom that enrolled adult patients with symptomatic chronic subdural hematoma. The patients were assigned in a 1:1 ratio to receive a 2-week tapering course of oral dexamethasone, starting at 8 mg twice daily, or placebo. The decision to surgically evacuate the hematoma was made by the treating clinician. The primary outcome was a score of 0 to 3, representing a favorable outcome, on the modified Rankin scale at 6 months after randomization; scores range from 0 (no symptoms) to 6 (death).

Results: From August 2015 through November 2019, a total of 748 patients were included in the trial after randomization - 375 were assigned to the dexamethasone group and 373 to the placebo group. The mean age of the patients was 74 years, and 94% underwent surgery to evacuate their hematomas during the index admission; 60% in both groups had a score of 1 to 3 on the modified Rankin scale at admission. In a modified intention-to-treat analysis that excluded the patients who withdrew consent for participation in the trial or who were lost to follow-up, leaving a total of 680 patients, a favorable outcome was reported in 286 of 341 patients (83.9%) in the dexamethasone group and in 306 of 339 patients (90.3%) in the placebo group (difference, -6.4 percentage points [95% confidence interval, -11.4 to -1.4] in favor of the placebo group; P = 0.01). Among the patients with available data, repeat surgery for recurrence of the hematoma was performed in 6 of 349 patients (1.7%) in the dexamethasone group and in 25 of 350 patients (7.1%) in the placebo group. More adverse events occurred in the dexamethasone group than in the placebo group.

Conclusions: Among adults with symptomatic chronic subdural hematoma, most of whom had undergone surgery to remove their hematomas during the index admission, treatment with dexamethasone resulted in fewer favorable outcomes and more adverse events than placebo at 6 months, but fewer repeat operations were performed in the dexamethasone group. (Funded by the National Institute for Health Research Health Technology Assessment Programme; Dex-CSDH ISRCTN number, ISRCTN80782810.).
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http://dx.doi.org/10.1056/NEJMoa2020473DOI Listing
December 2020

Impact of Surgery on Older Patients Hospitalized With an Acute Abdomen: Findings From the Older Persons Surgical Outcome Collaborative.

Front Surg 2020 16;7:583653. Epub 2020 Nov 16.

Department of Geriatric Medicine, Cardiff University, Cardiff, United Kingdom.

The impact of surgery compared to non-surgical management of older general surgical patients is not well researched. We examined the association between management and adverse outcomes in a cohort of emergency general surgery patients aged > 65 years. This multi-center study included 727 patients (mean+/-SD, 77.1 ± 8.2 years, 54% female) admitted to five UK hospitals. Data were analyzed using multi-level crude and multivariable logistic regression. Outcomes were: mortality at Day 30 and 90, length of stay, and readmission within 30 days of discharge. Covariates assessed were management approach, age, sex, frailty, polypharmacy, anemia, and hypoalbuminemia. Approximately 25% of participants ( = 185) underwent emergency surgery. Frailty and albumin were associated with mortality at 30 (frailty OR = 3.52 [95% CI 1.66-7.49], albumin OR = 3.78 ([95% CI 1.53-9.31]), and 90 days post discharge (frailty OR = 3.20 [95% CI 1.86-5.51], albumin OR=3.25 [95% CI 1.70-6.19]) and readmission (frailty OR = 1.56 [95% CI (1.04-2.35)]). Surgically managed patients and frailty had increased odds of prolonged hospitalization (surgery OR = 5.69 [95% CI 3.67-8.80], frailty OR = 2.17 [95% CI 1.46-3.23]). We found the impact of surgery on length of hospitalization in older surgical patients is substantial. Whether early comprehensive geriatric assessment and post-op rehabilitation would improve this outcome require further evaluation.
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http://dx.doi.org/10.3389/fsurg.2020.583653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705344PMC
November 2020

Acute Myocardial Infarction in Autoimmune Rheumatologic Disease: A Nationwide Analysis of Clinical Outcomes and Predictors of Management Strategy.

Mayo Clin Proc 2021 02 26;96(2):388-399. Epub 2020 Nov 26.

Keele Cardiovascular Research Group, Centre for Prognosis Research, Institutes of Applied Clinical Science and Primary Care and Health Sciences, Keele University, UK; Department of Cardiology, Royal Stoke University Hospital, Stoke-on-Trent, UK; Department of Medicine (Cardiology), Thomas Jefferson University Hospital, Philadelphia, PA. Electronic address:

Objectives: To examine national-level differences in management strategies and outcomes in patients with autoimmune rheumatic disease (AIRD) with acute myocardial infarction (AMI) from 2004 through 2014.

Methods: All AMI hospitalizations were analyzed from the National Inpatient Sample, stratified according to AIRD diagnosis into 4 groups: no AIRD, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and systemic sclerosis (SSC). The associations between AIRD subtypes and (1) receipt of coronary angiography and percutaneous coronary intervention (PCI) and (2) clinical outcomes were examined compared with patients without AIRD.

Results: Of 6,747,797 AMI hospitalizations, 109,983 patients (1.6%) had an AIRD diagnosis (RA: 1.3%, SLE: 0.3%, and SSC: 0.1%). The prevalence of RA rose from 1.0% (2004) to 1.5% (2014), and SLE and SSC remained stable. Patients with SLE were less likely to receive invasive management (odds ratio [OR] [95% CI]: coronary angiography-0.87; 0.84 to 0.91; PCI-0.93; 0.90 to 0.96), whereas no statistically significant differences were found in the RA and SSC groups. Subsequently, the ORs (95% CIs) of mortality (1.15; 1.07 to 1.23) and bleeding (1.24; 1.16 to 1.31) were increased in patients with SLE; SSC was associated with increased ORs (95% CIs) of major adverse cardiovascular and cerebrovascular events (1.52; 1.38 to 1.68) and mortality (1.81; 1.62 to 2.02) but not bleeding or stroke; the RA group was at no increased risk for any complication.

Conclusion: In a nationwide cohort of AMI hospitalizations we found lower use of invasive management in patients with SLE and worse outcomes after AMI in patients with SLE and SSC compared with those without AIRD.
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http://dx.doi.org/10.1016/j.mayocp.2020.04.044DOI Listing
February 2021

Trends, management and outcomes of acute myocardial infarction in chronic liver disease.

Int J Clin Pract 2021 Apr 30;75(4):e13841. Epub 2020 Nov 30.

Keele Cardiovascular Research Group, Centre for Prognosis Research, Institutes of Applied Clinical Science and Primary Care and Health Sciences, Keele University, Keele, United Kingdom.

Aims: There are limited data on the management and outcomes of chronic liver disease (CLD) patients presenting with acute myocardial infarction (AMI), particularly according to the subtype of CLD.

Methods: Using the Nationwide Inpatient Sample (2004-2015), we examined outcomes of AMI patients stratified by severity and sub-types of CLD. Multivariable logistic regression was performed to assess the adjusted odds ratios (aOR) of receipt of invasive management and adverse outcomes in CLD groups compared with no-CLD.

Results: Of 7 024 723 AMI admissions, 54 283 (0.8%) had a CLD diagnosis. CLD patients were less likely to undergo coronary angiography (CA) and percutaneous coronary intervention (PCI) (aOR 0.62, 95%CI 0.60-0.63 and 0.59, 95%CI 0.58-0.60, respectively), and had increased odds of adverse outcomes including major adverse cardiovascular and cerebrovascular events (1.19, 95%CI 1.15-1.23), mortality (1.30, 95%CI 1.25-1.34) and major bleeding (1.74, 95%CI 1.67-1.81). In comparison to the non-severe CLD sub-groups, patients with all forms of severe CLD had the lower utilization of CA and PCI (P < .05). Among severe CLD patients, those with alcohol-related liver disease (ALD) had the lowest utilization of CA and PCI; patients with ALD and other CLD (OCLD) had more adverse outcomes than the viral hepatitis sub-group (P < .05).

Conclusions: CLD patients presenting with AMI are less likely to receive invasive management and are associated with worse clinical outcomes. Further differences are observed depending on the type as well as severity of CLD, with the worst management and clinical outcomes observed in those with severe ALD and OCLD.
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http://dx.doi.org/10.1111/ijcp.13841DOI Listing
April 2021

Anticholinergic medication exposure predicts poor physical capability: Findings from a large prospective cohort study in England.

Maturitas 2020 Dec 25;142:55-63. Epub 2020 Jul 25.

Ageing Clinical & Experimental Research (ACER) Team, Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, UK; Department of Medicine for the Elderly, Aberdeen Royal Infirmary, Aberdeen, UK. Electronic address:

Objectives: To examine whether anticholinergic medication exposure in middle and late life is associated with physical capability.

Study Design: We used data from 8477 men and women who had enrolled in the European Prospective Investigation of Cancer-Norfolk study at baseline (1HC; 1993-1997) and who had attended its third health examination (3HC; 2004-2010). Medication history at the 1HC and 3HC was used to score participants according to the Anticholinergic Cognitive Burden (ACB) Scale at baseline and 3HC; participants were categorised as ACB = 0, ACB = 1, ACB>2.

Main Outcome Measure: At 3HC, physical capability was objectively measured by: usual walking speed, maximum grip strength, timed chair stands speed (TCSS) and standing balance. Linear and logistic regression models examined prospective and cross-sectional associations between ACB and physical capability, controlling for co-morbidity, sociodemographic and lifestyle factors.

Results: The analyses included 3386 men and 4110 women who were 56.4 (SD 7.9) and 55.0 (7.7) years old respectively at baseline and 69.4 (8.1) and 67.9 (8.0) years old at follow-up. Significant cross-sectional and prospective relationships were observed for all physical capability measures in women, except grip strength. For example, women with ACB ≥ 2 compared with ACB = 0 at baseline had 0.07 m/s (95 % CI -0.11, -0.03) slower usual walking speed, 2.61 stands/min (-4.17, -1.05) slower TCSS and higher odds of being unable to complete a tandem stand (odds ratio 2.40, 95 % CI 1.53, 3.76). These trends were observed in men but were less consistent in prospective analyses.

Conclusion: Exposure to anticholinergic medication predicts poor physical capability and is a potentially reversible risk factor.
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http://dx.doi.org/10.1016/j.maturitas.2020.07.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656240PMC
December 2020

Association of Circulating Monocyte Chemoattractant Protein-1 Levels With Cardiovascular Mortality: A Meta-analysis of Population-Based Studies.

JAMA Cardiol 2020 Nov 4. Epub 2020 Nov 4.

Institute for Stroke and Dementia Research, University Hospital, Ludwig-Maximilians-University, Munich, Germany.

Importance: Human genetics and studies in experimental models support a key role of monocyte-chemoattractant protein-1 (MCP-1) in atherosclerosis. Yet, the associations of circulating MCP-1 levels with risk of coronary heart disease and cardiovascular death in the general population remain largely unexplored.

Objective: To explore whether circulating levels of MCP-1 are associated with risk of incident coronary heart disease, myocardial infarction, and cardiovascular mortality in the general population.

Data Sources And Selection: Population-based cohort studies, identified through a systematic review, that have examined associations of circulating MCP-1 levels with cardiovascular end points.

Data Extraction And Synthesis: Using a prespecified harmonized analysis plan, study-specific summary data were obtained from Cox regression models after excluding individuals with overt cardiovascular disease at baseline. Derived hazard ratios (HRs) were synthesized using random-effects meta-analyses.

Main Outcomes And Measures: Incident coronary heart disease (myocardial infarction, coronary revascularization, and unstable angina), nonfatal myocardial infarction, and cardiovascular death (from cardiac or cerebrovascular causes).

Results: The meta-analysis included 7 cohort studies involving 21 401 individuals (mean [SD] age, 53.7 [10.2] years; 10 012 men [46.8%]). Mean (SD) follow-up was 15.3 (4.5) years (326 392 person-years at risk). In models adjusting for age, sex, and race/ethnicity, higher MCP-1 levels at baseline were associated with increased risk of coronary heart disease (HR per 1-SD increment in MCP-1 levels: 1.06 [95% CI, 1.01-1.11]; P = .01), nonfatal myocardial infarction (HR, 1.07 [95% CI, 1.01-1.13]; P = .02), and cardiovascular death (HR, 1.12 [95% CI, 1.05-1.20]; P < .001). In analyses comparing MCP-1 quartiles, these associations followed dose-response patterns. After additionally adjusting for vascular risk factors, the risk estimates were attenuated, but the associations of MCP-1 levels with cardiovascular death remained statistically significant, as did the association of MCP-1 levels in the upper quartile with coronary heart disease. There was no significant heterogeneity; the results did not change in sensitivity analyses excluding events occurring in the first 5 years after MCP-1 measurement, and the risk estimates were stable after additional adjustments for circulating levels of interleukin-6 and high-sensitivity C-reactive protein.

Conclusions And Relevance: Higher circulating MCP-1 levels are associated with higher long-term cardiovascular mortality in community-dwelling individuals free of overt cardiovascular disease. These findings provide further support for a key role of MCP-1-signaling in cardiovascular disease.
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http://dx.doi.org/10.1001/jamacardio.2020.5392DOI Listing
November 2020

Frailty and mortality in patients with COVID-19 - Authors' reply.

Lancet Public Health 2020 11;5(11):e582

Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

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http://dx.doi.org/10.1016/S2468-2667(20)30224-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588175PMC
November 2020

Hypertensive Disorders of Pregnancy (HDP) and the Risk of Common Cancers in Women: Evidence from the European Prospective Investigation into Cancer (EPIC)-Norfolk Prospective Population-Based Study.

Cancers (Basel) 2020 Oct 23;12(11). Epub 2020 Oct 23.

Aberdeen Centre for Women's Health Research, Institute of Applied Health Sciences, University of Aberdeen, Aberdeen AB25 2ZL, UK.

Purpose: The purpose was to determine the association between HDP and cancer in a UK cohort.

Methods: Between 1993 and 1997, participants from the EPIC-Norfolk cohort attended baseline health-checks and completed questionnaires, where a history of HDP was collected. Incident cancer cases were identified through NHS record linkage until March 2016. Univariable and multivariable logistic regression analyses were employed to determine the association between HDP and odds of cancer, with adjustment for potential confounders including co-morbidities, sociodemographic, lifestyle and reproductive factors.

Results: 13,562 women were included after excluding prevalent cancer cases and women with no pregnancies. 2919 (21.5%) reported HDP and 2615 incident cancers occurred during mean follow up of 19 years. Median age (IQR) at baseline for incident cancer was 60.8 (±14.8) years. Among incident cancer cases, 578 (22.1%) had HDP. In multivariable analyses, HDP had odds ratio (OR) 1.06; 95% CI 0.95-1.18 for incident cancer. The ORs (95% CIs) for common site-specific cancers including breast, colorectal, lung, ovarian and endometrial cancers were 1.06 (0.88-1.28), 1.15 (0.92-1.45), 0.96 (0.68-1.35), 1.30 (0.93-1.83) and 1.16 (0.80-1.67).

Conclusion: We found no association between HDP and cancer risk. Further studies are required to confirm and account for any underlying genetic factors involved in pregnancy-related exposures and cancer risk.
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http://dx.doi.org/10.3390/cancers12113100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690818PMC
October 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

The Clinical Frailty Scale: Estimating the Prevalence of Frailty in Older Patients Hospitalised with COVID-19. The COPE Study.

Geriatrics (Basel) 2020 Sep 21;5(3). Epub 2020 Sep 21.

Division of Population Medicine, Aneurin Bevan UHB, Cardiff University, Cardiff CF14 4XN, UK.

Frailty assessed using Clinical Frailty Scale (CFS) is a good predictor of adverse clinical events including mortality in older people. CFS is also an essential criterion for determining ceilings of care in people with COVID-19. Our aims were to assess the prevalence of frailty in older patients hospitalised with COVID-19, their sex and age distribution, and the completion rate of the CFS tool in evaluating frailty. Data were collected from thirteen sites. CFS was assessed routinely at the time of admission to hospital and ranged from 1 (very fit) to 9 (terminally ill). The completion rate of the CFS was assessed. The presence of major comorbidities such as diabetes and cardiovascular disease was noted. A total of 1277 older patients with COVID-19, aged ≥ 65 (79.9 ± 8.1) years were included in the study, with 98.5% having fully completed CFS. The total prevalence of frailty (CFS ≥ 5) was 66.9%, being higher in women than men (75.2% vs. 59.4%, < 0.001). Frailty was found in 161 (44%) patients aged 65-74 years, 352 (69%) in 75-84 years, and 341 (85%) in ≥85 years groups, and increased across the age groups (<0.0001, test for trend). Conclusion: Frailty was prevalent in our cohort of older people admitted to hospital with COVID-19. This indicates that older people who are also frail, who go on to contract COVID-19 may have disease severity significant enough to warrant hospitalization. These data may help inform health care planners and targeted interventions and appropriate management for the frail older person.
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http://dx.doi.org/10.3390/geriatrics5030058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554723PMC
September 2020

Can cardiovascular risk management be improved by shared care with general practice to prevent cognitive decline following stroke/TIA? A feasibility randomised controlled trial (SERVED memory).

BMC Geriatr 2020 09 17;20(1):353. Epub 2020 Sep 17.

Ageing and Stroke Medicine, Norwich Medical School, University of East Anglia, Bob Champion Research Building, James Watson Road, Norwich, UK.

Background: Cognitive impairment and dementia following cerebrovascular disease are increasingly common in the UK. One potential strategy to prevent post-stroke cognitive decline is multimodal vascular risk factor management. However, its efficacy remains uncertain and its application in vulnerable patients with incident cerebrovascular disease and early cognitive impairment has not been assessed. The primary aim of this study was to assess the feasibility of recruitment and retention of patients with early cognitive impairment post-stroke or transient ischaemic attack (TIA) to a trial of enhanced vascular risk factor management combining primary and secondary care.

Methods: In this single centre, open label trial adults with a recent stroke or TIA and mild cognitive impairment (MCI) were randomised 1:1 to a three-monthly multimodal vascular risk factor intervention jointly delivered by the trial team and General Practitioner (GP), or control (defined as usual care from the GP). Chosen risk factors were blood pressure (BP), total cholesterol, blood glucose (HbA1C) in those with diabetes, and heart rate and adequacy of anticoagulation in those with atrial fibrillation (AF). Similar patients with normal cognition were enrolled in an embedded observational cohort and also received usual care from the GP. Repeat cognitive screening was undertaken in all participants after 12 months.

Results: Seventy three participants were recruited to the randomised trial and 94 to the observational cohort (21.8% of those screened). From the randomised trial 35/73 (47.9%) dropped out before final follow-up. In all groups guideline based rates of risk factor control were mostly poor at baseline and did not significantly improve during follow-up. The observational cohort demonstrated greater decline in cognitive test scores at 12 months, with no difference between the randomised groups.

Conclusions: Recruitment to such a study was feasible, but retention of participants was difficult and generally poor rates of risk factor control suggested insufficient application of the intervention. Consequently, successful scaling up of the trial would require protocol changes with less reliance on primary care services. Any future trial should include participants with normal cognition post-stroke as they may be at greatest risk of cognitive decline.

Trial Registration: ISRCTN, ISRCTN42688361 . Registered 16 April 2015.
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http://dx.doi.org/10.1186/s12877-020-01760-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499986PMC
September 2020

Temporal Trends in Pregnancy-Associated Stroke and Its Outcomes Among Women With Hypertensive Disorders of Pregnancy.

J Am Heart Assoc 2020 08 29;9(15):e016182. Epub 2020 Jul 29.

Keele Cardiovascular Research Group School of Primary, Community and Social Care Keele University Staffordshire United Kingdom.

Background Stroke is a serious complication of hypertensive disorders of pregnancy (HDP), with potentially severe and long-term sequelae. However, the temporal trends, predictors, and outcomes of stroke in women with HDP at delivery remain unknown. Methods and Results All HDP delivery hospitalizations with or without stroke event (ischemic, hemorrhagic, or unspecified) between 2004 and 2014 in the United States National Inpatient Sample were analyzed to examine incidence, predictors, and prognostic impact of stroke. Of 4 240 284 HDP delivery hospitalizations, 3391 (0.08%) women had stroke. While the prevalence of HDP increased over time, incident stroke rates decreased from 10 to 6 per 10 000 HDP delivery hospitalizations between 2004 and 2014. Women with stroke were increasingly multimorbid, with some risk factors being more strongly associated with ischemic strokes, including congenital heart disease, peripheral vascular disease, dyslipidemia, and sickle cell disease. Delivery complications were also associated with stroke, including cesarean section (odds ratio [OR], 1.58; 95% CI, 1.33-1.86), postpartum hemorrhage (OR, 1.91; 95% CI, 1.33-1.86), and maternal mortality (OR, 99.78; 95% CI, 59.15-168.31), independently of potential confounders. Women with stroke had longer hospital stays (median, 6 versus 3 days), higher hospital charges (median, $14 655 versus $4762), and a higher proportion of nonroutine discharge locations (38% versus 4%). Conclusions The incidence of stroke in women with HDP has declined over time. While a relatively rare event, identification of women at highest risk of ischemic or hemorrhagic stroke on admission for delivery is important to reduce long-term sequelae.
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http://dx.doi.org/10.1161/JAHA.120.016182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792242PMC
August 2020

Increasing prevalence of anticholinergic medication use in older people in England over 20 years: cognitive function and ageing study I and II.

BMC Geriatr 2020 07 31;20(1):267. Epub 2020 Jul 31.

Aston University, Birmingham, B4 7ET, UK.

Background: Anticholinergic medication use is linked with increased cognitive decline, dementia, falls and mortality, and their use should be limited in older people. Here we estimate the prevalence of anticholinergic use in England's older population in 1991 and 2011, and describe changes in use by participant's age, sex, cognition and disability.

Methods: We compared data from participants aged 65+ years from the Cognitive Function and Ageing Studies (CFAS I and II), collected during 1990-1993 (N = 7635) and 2008-2011 (N = 7762). We estimated the prevalence of potent anticholinergic use (Anticholinergic Cognitive Burden [ACB] score = 3) and average anticholinergic burden (sum of ACB scores), using inverse probability weights standardised to the 2011 UK population. These were stratified by age, sex, Mini-Mental State Examination score, and activities of daily living (ADL) or instrumental ADL (IADL) disability.

Results: Prevalence of potent anticholinergic use increased from 5.7% (95% Confidence Interval [CI] 5.2-6.3%) of the older population in 1990-93 to 9.9% (9.3-10.7%) in 2008-11, adjusted odds ratio of 1.90 (95% CI 1.67-2.16). People with clinically significant cognitive impairment (MMSE [Mini Mental State Examination] 21 or less) were the heaviest users of potent anticholinergics in CFAS II (16.5% [95% CI 12.0-22.3%]). Large increases in the prevalence of the use medication with 'any' anticholinergic activity were seen in older people with clinically significant cognitive impairment (53.3% in CFAS I to 71.5% in CFAS II).

Conclusions: Use of potent anticholinergic medications nearly doubled in England's older population over 20 years with some of the greatest increases amongst those particularly vulnerable to anticholinergic side-effects.
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http://dx.doi.org/10.1186/s12877-020-01657-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393714PMC
July 2020

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

The effect of frailty on survival in patients with COVID-19 (COPE): a multicentre, European, observational cohort study.

Lancet Public Health 2020 08 30;5(8):e444-e451. Epub 2020 Jun 30.

Department of Surgery and Care of the Elderly, Southmead Hospital, North Bristol NHS Trust, Bristol, UK. Electronic address:

Background: The COVID-19 pandemic has placed unprecedented strain on health-care systems. Frailty is being used in clinical decision making for patients with COVID-19, yet the prevalence and effect of frailty in people with COVID-19 is not known. In the COVID-19 in Older PEople (COPE) study we aimed to establish the prevalence of frailty in patients with COVID-19 who were admitted to hospital and investigate its association with mortality and duration of hospital stay.

Methods: This was an observational cohort study conducted at ten hospitals in the UK and one in Italy. All adults (≥18 years) admitted to participating hospitals with COVID-19 were included. Patients with incomplete hospital records were excluded. The study analysed routinely generated hospital data for patients with COVID-19. Frailty was assessed by specialist COVID-19 teams using the clinical frailty scale (CFS) and patients were grouped according to their score (1-2=fit; 3-4=vulnerable, but not frail; 5-6=initial signs of frailty but with some degree of independence; and 7-9=severe or very severe frailty). The primary outcome was in-hospital mortality (time from hospital admission to mortality and day-7 mortality).

Findings: Between Feb 27, and April 28, 2020, we enrolled 1564 patients with COVID-19. The median age was 74 years (IQR 61-83); 903 (57·7%) were men and 661 (42·3%) were women; 425 (27·2%) had died at data cutoff (April 28, 2020). 772 (49·4%) were classed as frail (CFS 5-8) and 27 (1·7%) were classed as terminally ill (CFS 9). Compared with CFS 1-2, the adjusted hazard ratios for time from hospital admission to death were 1·55 (95% CI 1·00-2·41) for CFS 3-4, 1·83 (1·15-2·91) for CFS 5-6, and 2·39 (1·50-3·81) for CFS 7-9, and adjusted odds ratios for day-7 mortality were 1·22 (95% CI 0·63-2·38) for CFS 3-4, 1·62 (0·81-3·26) for CFS 5-6, and 3·12 (1·56-6·24) for CFS 7-9.

Interpretation: In a large population of patients admitted to hospital with COVID-19, disease outcomes were better predicted by frailty than either age or comorbidity. Our results support the use of CFS to inform decision making about medical care in adult patients admitted to hospital with COVID-19.

Funding: None.
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http://dx.doi.org/10.1016/S2468-2667(20)30146-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326416PMC
August 2020

Anticholinergic drugs and incident dementia, mild cognitive impairment and cognitive decline: a meta-analysis.

Age Ageing 2020 10;49(6):939-947

University of East Anglia, Norwich, UK.

Background: the long-term effect of the use of drugs with anticholinergic activity on cognitive function remains unclear.

Methods: we conducted a systematic review and meta-analysis of the relationship between anticholinergic drugs and risk of dementia, mild cognitive impairment (MCI) and cognitive decline in the older population. We identified studies published between January 2002 and April 2018 with ≥12 weeks follow-up between strongly anticholinergic drug exposure and the study outcome measurement. We pooled adjusted odds ratios (OR) for studies reporting any, and at least short-term (90+ days) or long-term (365+ days) anticholinergic use for dementia and MCI outcomes, and standardised mean differences (SMD) in global cognition test scores for cognitive decline outcomes. Statistical heterogeneity was measured using the I2 statistic and risk of bias using ROBINS-I.

Results: twenty-six studies (including 621,548 participants) met our inclusion criteria. 'Any' anticholinergic use was associated with incident dementia (OR 1.20, 95% confidence interval [CI] 1.09-1.32, I2 = 86%). Short-term and long-term use were also associated with incident dementia (OR 1.23, 95% CI 1.17-1.29, I2 = 2%; and OR 1.50, 95% CI 1.22-1.85, I2 = 90%). 'Any' anticholinergic use was associated with cognitive decline (SMD 0.15; 95% CI 0.09-0.21, I2 = 3%) but showed no statistically significant difference for MCI (OR 1.24, 95% CI 0.97-1.59, I2 = 0%).

Conclusions: anticholinergic drug use is associated with increased dementia incidence and cognitive decline in observational studies. However, a causal link cannot yet be inferred, as studies were observational with considerable risk of bias. Stronger evidence from high-quality studies is needed to guide the management of long-term use.
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http://dx.doi.org/10.1093/ageing/afaa090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583519PMC
October 2020

An overview of prevalence, determinants and health outcomes of polypharmacy.

Ther Adv Drug Saf 2020 12;11:2042098620933741. Epub 2020 Jun 12.

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

A high rate of polypharmacy is, in part, a consequence of the increasing proportion of multimorbidity in the ageing population worldwide. Our understanding of the potential harm of taking multiple medications in an older, multi-morbid population, who are likely to be on a polypharmacy regime, is limited. This is a narrative literature review that aims to appraise and summarise recent studies published about polypharmacy. We searched MEDLINE using the search terms (and its variations, e.g. multiple prescriptions, inappropriate drug use, etc.) in titles. Systematic reviews and original studies in English published between 2003 and 2018 were included. In this review, we provide current definitions of polypharmacy. We identify the determinants and prevalence of polypharmacy reported in different studies. Finally, we summarise some of the findings regarding the association between polypharmacy and health outcomes in older adults, with a focus on frailty, hospitalisation and mortality. Polypharmacy was most often defined in terms of the number of medications that are being taken by an individual at any given time. Our review showed that the prevalence of polypharmacy varied between 10% to as high as around 90% in different populations. Chronic conditions, demographics, socioeconomics and self-assessed health factors were independent predictors of polypharmacy. Polypharmacy was reported to be associated with various adverse outcomes after adjusting for health conditions. Optimising care for polypharmacy with valid, reliable measures, relevant to all patients, will improve the health outcomes of older adult population.
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http://dx.doi.org/10.1177/2042098620933741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294476PMC
June 2020

Anticholinergic burden in middle-aged women and recurrent falls in later life: findings from the Aberdeen prospective osteoporosis screening study (APOSS).

Ther Adv Drug Saf 2020 27;11:2042098620929852. Epub 2020 May 27.

School of Medicine, Medical Sciences and Nutrition, Ageing Clinical and Experimental Research (ACER) Team, University of Aberdeen, Room 4:013, Polwarth Building, Foresterhill, Aberdeen, Scotland, AB25 2ZD, UK Aberdeen Centre for Arthritis and Musculoskeletal Health, University of Aberdeen, UK Department of Medicine for the Elderly, NHS Grampian, Foresterhill Road, Aberdeen, UK.

Background: Anticholinergic burden (ACB) is a recognised risk factor for falls in older people; however, whether ACB in middle age predicts falls in later life is unknown.

Methods: We examined this association in the middle-aged women of the Aberdeen Prospective Osteoporosis Screening Study (APOSS). ACB was calculated at the second health visit (1997-1999, study baseline) using the Anticholinergic Cognitive Burden Scale. Outcomes were incidence of 1 fall and recurrent falls (⩾2 falls) during the 12 months prior to follow up 2007-2011. Multinomial logistic regression analyses adjusted for potential confounders including demographics, comorbidities and falls history.

Results: A total of 2125 women {mean age (standard deviation [SD]): 54.7 (2.2) years at baseline and 66.0 (2.2) years at follow up} were included. Prevalence of baseline ACB score of 0, 1 and ⩾2 was 87.1%, 7.3% and 5.6%, respectively. Compared with no ACB, ACB ⩾2 was associated with recurrent falls in the previous 12 months [adjusted odds ratio (OR): 2.34, 95% confidence interval (CI): 1.31, 4.19] at an average of 11 years after initial exposure. No such association was found for an ACB score of 1.

Conclusions: These findings highlight the potential negative effects of anticholinergic medications in middle age. While cautious use of anticholinergic medications is advisable, further longitudinal research should be conducted to confirm these findings before any specific clinical recommendations can be made.
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http://dx.doi.org/10.1177/2042098620929852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273562PMC
May 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

Protocol for the process evaluation of a cluster randomised controlled trial to determine the effectiveness and cost-effectiveness of independent pharmacist prescribing in care home: the CHIPPS study.

Trials 2020 May 29;21(1):439. Epub 2020 May 29.

School of Pharmacy, University of East Anglia, Norwich, UK.

Background: Prescribing, monitoring and administration of medicines in care homes could be improved. A cluster randomised controlled trial (RCT) is ongoing to evaluate the effectiveness of an independent prescribing pharmacist assuming responsibility for medicines management in care homes compared to usual care.

Aims And Objectives: To conduct a mixed-methods process evaluation of the RCT, in line with Medical Research Council (MRC) process evaluation guidance, to inform interpretation of main trial findings and if the service is found to be effective and efficient, to inform subsequent implementation.

Objectives: 1. To describe the intervention as delivered in terms of quality, quantity, adaptations and variations across triads and time. 2. To explore the effects of individual intervention components on the primary outcomes. 3. To investigate the mechanisms of impact. 4. To describe the perceived effectiveness of relevant intervention components [including pharmacist independent prescriber (PIP) training and care home staff training] from participant [general practitioner (GP), care home, PIP and resident/relative] perspectives. 5. To describe the characteristics of GP, care home, PIP and resident participants to assess reach. 6. To estimate the extent to which intervention delivery is normalised among the intervention healthcare professionals and related practice staff.

Methods: A mix of quantitative (surveys, record reviews) and qualitative (interviews) approaches will be used to collect data on the extent of the delivery of detailed tasks required to implement the new service, to collect data to confirm the mechanism of impact as hypothesised in the logic model, to collect explanatory process and final outcome data, and data on contextual factors which could have facilitated or hindered effective and efficient delivery of the service.

Discussion: Recruitment is ongoing and the trial should complete in early 2020. The systematic and comprehensive approach that is being adopted will ensure data is captured on all aspects of the study, and allow a full understanding of the implementation of the service and the RCT findings. With so many interrelated factors involved it is important that a process evaluation is undertaken to enable us to identify which elements of the service were deemed to be effective, explain any differences seen, and identify enablers, barriers and future adaptions.

Trial Registration: ISRCTN17847169. Date registered: 15 December 2017.
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http://dx.doi.org/10.1186/s13063-020-04264-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7257128PMC
May 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