nxin Li

Age-specific risks, severity, time course, and outcome of bleeding on long-term antiplatelet treatment after vascular events: a population-based cohort study

Summary Background Lifelong antiplatelet treatment is recommended after ischaemic vascular events, on the basis of trials done mainly in patients younger than 75 years. Upper gastrointestinal bleeding is a serious complication, but had low case fatality in trials of aspirin and is not generally thought to cause long-term disability. Consequently, although co-prescription of proton-pump inhibitors (PPIs) reduces upper gastrointestinal bleeds by 70–90%, uptake is low and guidelines are conflicting. We aimed to assess the risk, time course, and outcomes of bleeding on antiplatelet treatment for secondary prevention in patients of all ages. Methods We did a prospective population-based cohort study in patients with a first transient ischaemic attack, ischaemic stroke, or myocardial infarction treated with antiplatelet drugs (mainly aspirin based, without routine PPI use) after the event in the Oxford Vascular Study from 2002 to 2012, with follow-up until 2013. We determined type, severity, outcome (disability or death), and time course of bleeding requiring medical attention by face-to-face follow-up for 10 years. We estimated age-specific numbers needed to treat (NNT) to prevent upper gastrointestinal bleeding with routine PPI co-prescription on the basis of Kaplan–Meier risk estimates and relative risk reduction estimates from previous trials. Findings 3166 patients (1582 [50%] aged ≥75 years) had 405 first bleeding events (n=218 gastrointestinal, n=45 intracranial, and n=142 other) during 13 509 patient-years of follow-up. Of the 314 patients (78%) with bleeds admitted to hospital, 117 (37%) were missed by administrative coding. Risk of non-major bleeding was unrelated to age, but major bleeding increased steeply with age (≥75 years hazard ratio [HR] 3·10, 95% CI 2·27–4·24; p<0·0001), particularly for fatal bleeds (5·53, 2·65–11·54; p<0·0001), and was sustained during long-term follow-up. The same was true of major upper gastrointestinal bleeds (≥75 years HR 4·13, 2·60–6·57; p<0·0001), particularly if disabling or fatal (10·26, 4·37–24·13; p<0·0001). At age 75 years or older, major upper gastrointestinal bleeds were mostly disabling or fatal (45 [62%] of 73 patients vs 101 [47%] of 213 patients with recurrent ischaemic stroke), and outnumbered disabling or fatal intracerebral haemorrhage (n=45 vs n=18), with an absolute risk of 9·15 (95% CI 6·67–12·24) per 1000 patient-years. The estimated NNT for routine PPI use to prevent one disabling or fatal upper gastrointestinal bleed over 5 years fell from 338 for individuals younger than 65 years, to 25 for individuals aged 85 years or older. Interpretation In patients receiving aspirin-based antiplatelet treatment without routine PPI use, the long-term risk of major bleeding is higher and more sustained in older patients in practice than in the younger patients in previous trials, with a substantial risk of disabling or fatal upper gastrointestinal bleeding. Given that half of the major bleeds in patients aged 75 years or older were upper gastrointestinal, the estimated NNT for routine PPI use to prevent such bleeds is low, and co-prescription should be encouraged. Funding Wellcome Trust, Wolfson Foundation, British Heart Foundation, Dunhill Medical Trust, National Institute of Health Research (NIHR), and the NIHR Oxford Biomedical Research Centre.

Age-Specific Incidence, Outcome, Cost, and Projected Future Burden of Atrial Fibrillation–Related Embolic Vascular Events A Population-Based Study

Background— Prevalence of atrial fibrillation (AF) is >10% at age ≥80 years, but the impact of population aging on rates of AF-related ischemic events is uncertain. Methods and Results— We studied age-specific incidence, outcome, and cost of all AF-related incident strokes and systemic emboli from 2002 to 2012 in the Oxford Vascular Study (OXVASC). We determined time trends in incidence of AF-related stroke in comparison with a sister study in 1981 to 1986, extrapolated numbers to the UK population and projected future numbers. Of 3096 acute cerebral or peripheral vascular events in the 92 728 study population, 383 incident ischemic strokes and 71 systemic emboli were related to AF, of which 272 (59.9%) occurred at ≥80 years. Of 597 fatal or disabling incident ischemic strokes, 262 (43.9%) were AF-related. Numbers of AF-related ischemic strokes at age ≥80 years increased nearly 3-fold from 1981–1986 to 2002–2012 (extrapolated to the United Kingdom: 6621 to 18 176 per year), due partly to increased age-specific incidence (relative rate 1.52, 95% confidence interval 1.31-1.77, P=0.001), with potentially preventable AF-related events at age ≥80 years costing the United Kingdom £374 million per year. At current incidence rates, numbers of AF-related embolic events at age ≥80 years will treble again by 2050 (72 974/year), with 83.5% of all events occurring in this age group. Conclusions— Numbers of AF-related incident ischemic strokes at age ≥80 years have trebled over the last 25 years, despite the introduction of anticoagulants, and are projected to treble again by 2050, along with the numbers of systemic emboli. Improved prevention in older people with AF should be a major public health priority.

Biases in detection of apparent “weekend effect” on outcome with administrative coding data: population based study of stroke

Objectives To determine the accuracy of coding of admissions for stroke on weekdays versus weekends and any impact on apparent outcome. Design Prospective population based stroke incidence study and a scoping review of previous studies of weekend effects in stroke. Setting Primary and secondary care of all individuals registered with nine general practices in Oxfordshire, United Kingdom (OXVASC, the Oxford Vascular Study). Participants All patients with clinically confirmed acute stroke in OXVASC identified with multiple overlapping methods of ascertainment in 2002-14 versus all acute stroke admissions identified by hospital diagnostic and mortality coding alone during the same period. Main outcomes measures Accuracy of administrative coding data for all patients with confirmed stroke admitted to hospital in OXVASC. Difference between rates of “false positive” or “false negative” coding for weekday and weekend admissions. Impact of inaccurate coding on apparent case fatality at 30 days in weekday versus weekend admissions. Weekend effects on outcomes in patients with confirmed stroke admitted to hospital in OXVASC and impacts of other potential biases compared with those in the scoping review. Results Among 92 728 study population, 2373 episodes of acute stroke were ascertained in OXVASC, of which 826 (34.8%) mainly minor events were managed without hospital admission, 60 (2.5%) occurred out of the area or abroad, and 195 (8.2%) occurred in hospital during an admission for a different reason. Of 1292 local hospital admissions for acute stroke, 973 (75.3%) were correctly identified by administrative coding. There was no bias in distribution of weekend versus weekday admission of the 319 strokes missed by coding. Of 1693 admissions for stroke identified by coding, 1055 (62.3%) were confirmed to be acute strokes after case adjudication. Among the 638 false positive coded cases, patients were more likely to be admitted on weekdays than at weekends (536 (41.0%) v 102 (26.5%); P<0.001), partly because of weekday elective admissions after previous stroke being miscoded as new stroke episodes (267 (49.8%) v 26 (25.5%); P<0.001). The 30 day case fatality after these elective admissions was lower than after confirmed acute stroke admissions (11 (3.8%) v 233 (22.1%); P<0.001). Consequently, relative 30 day case fatality for weekend versus weekday admissions differed (P<0.001) between correctly coded acute stroke admissions and false positive coding cases. Results were consistent when only the 1327 emergency cases identified by “admission method” from coding were included, with more false positive cases with low case fatality (35 (14.7%)) being included for weekday versus weekend admissions (190 (19.5%) v 48 (13.7%), P<0.02). Among all acute stroke admissions in OXVASC, there was no imbalance in baseline stroke severity for weekends versus weekdays and no difference in case fatality at 30 days (adjusted odds ratio 0.85, 95% confidence interval 0.63 to 1.15; P=0.30) or any adverse “weekend effect” on modified Rankin score at 30 days (0.78, 0.61 to 0.99; P=0.04) or one year (0.76, 0.59 to 0.98; P=0.03) among incident strokes. Conclusion Retrospective studies of UK administrative hospital coding data to determine “weekend effects” on outcome in acute medical conditions, such as stroke, can be undermined by inaccurate coding, which can introduce biases that cannot be reliably dealt with by adjustment for case mix.

BIANCA (Brain Intensity AbNormality Classification Algorithm): A new tool for automated segmentation of white matter hyperintensities.

Reliable quantification of white matter hyperintensities of presumed vascular origin (WMHs) is increasingly needed, given the presence of these MRI findings in patients with several neurological and vascular disorders, as well as in elderly healthy subjects. We present BIANCA (Brain Intensity AbNormality Classification Algorithm), a fully automated, supervised method for WMH detection, based on the k-nearest neighbour (k-NN) algorithm. Relative to previous k-NN based segmentation methods, BIANCA offers different options for weighting the spatial information, local spatial intensity averaging, and different options for the choice of the number and location of the training points. BIANCA is multimodal and highly flexible so that the user can adapt the tool to their protocol and specific needs. We optimised and validated BIANCA on two datasets with different MRI protocols and patient populations (a “predominantly neurodegenerative” and a “predominantly vascular” cohort). BIANCA was first optimised on a subset of images for each dataset in terms of overlap and volumetric agreement with a manually segmented WMH mask. The correlation between the volumes extracted with BIANCA (using the optimised set of options), the volumes extracted from the manual masks and visual ratings showed that BIANCA is a valid alternative to manual segmentation. The optimised set of options was then applied to the whole cohorts and the resulting WMH volume estimates showed good correlations with visual ratings and with age. Finally, we performed a reproducibility test, to evaluate the robustness of BIANCA, and compared BIANCA performance against existing methods. Our findings suggest that BIANCA, which will be freely available as part of the FSL package, is a reliable method for automated WMH segmentation in large cross-sectional cohort studies.

Age- and sex-specific rates of leukoaraiosis in TIA and stroke patients: population-based study.

Objective: To determine any sex differences in age-specific prevalence or severity of leukoaraiosis, a marker of white matter ischemia, in population-based and clinic cohorts of TIA/stroke and in a systematic review of the literature. Methods: Age-specific sex differences were calculated for both CT and MRI in the Oxford Vascular Study (OXVASC) and in an MRI-based clinic cohort. We pooled odds ratios (ORs) for leukoaraiosis in women vs men from published studies by fixed-effect meta-analysis, stratified by patient characteristics (stroke vs nonstroke) and CT vs MRI. Results: Among 10 stroke studies (all CT-based), leukoaraiosis was most frequent in women (OR = 1.42, 95% confidence interval [CI] 1.27–1.57, p < 0.0001), with little heterogeneity between studies (p = 0.28). However, no such excess was seen in 10 reports of nonstroke cohorts (0.91, 0.67–1.24, p = 0.56). Moreover, excess leukoaraiosis in women on CT-imaging in OXVASC (1.38, 1.15–1.67, p = 0.001) was explained by their older age (age-adjusted OR = 1.01, 0.82–1.25, p = 0.90). Leukoaraiosis was more severe in older (≥75) women (CT-1.50, 1.14–1.97, p = 0.004 in OXVASC; MRI-1.70, 1.17–2.48, p = 0.006 in OXVASC and clinic cohort). However, leukoaraiosis was independently associated with early mortality (hazard ratio = 1.46, 1.23–1.73, p < 0.0001), suggesting that comparisons in older age groups will be biased by prior premature death of men with leukoaraiosis. Sex differences in severity of leukoaraiosis were not addressed in previous studies. Conclusions: Previously reported excess leukoaraiosis in women with TIA/stroke is likely to be confounded by age and apparently greater severity in older women is likely to be biased by premature death in men with leukoaraiosis.

Validation of the Montreal Cognitive Assessment Versus Mini-Mental State Examination Against Hypertension and Hypertensive Arteriopathy After Transient Ischemic Attack or Minor Stroke

Background and Purpose— Lack of reduced cognitive impairment with blood pressure (BP) lowering in trials may reflect use of the Mini-Mental State Examination (MMSE), which is insensitive to mild cognitive impairment after cerebrovascular events compared with the Montreal Cognitive Assessment. We determined relationships between impairment on MMSE versus Montreal Cognitive Assessment (MoCA) with the major physiological determinant of vascular cognitive impairment: hypertension and hypertensive arteriopathy. Methods— Cognitive impairment in consecutive patients 6 months after transient ischemic attack or minor stroke was defined as significant, mild, or none (MMSE<23, 23–26, ≥27; MoCA<20, 20–24, ≥25) and related to 20 premorbid systolic BP readings, home BP measurement (3 measurements, 3×daily for 1 month), and hypertensive arteriopathy (creatinine, stroke versus transient ischemic attack, leukoaraiosis) by ordinal regression. Results— Of 463 patients, 45% versus 28% had at least mild cognitive impairment on the MoCA versus MMSE (P<0.001). Hypertensive arteriopathy was more strongly associated with cognitive impairment on the MoCA than MMSE (creatinine: odds ratio=3.99; 95% confidence interval, 2.06–7.73 versus 2.16, 1.08–4.33; event: 1.53, 1.06–2.19 versus 1.23, 0.81–1.85; leukoaraiosis: 2.09, 1.42–3.06 versus 1.34, 0.87–2.07). Premorbid and home BP measurement systolic BP were more strongly associated with impairment on vascular subdomains of the MoCA than MMSE (odds ratio/10 mm Hg: visuospatial 1.29 versus 1.05; attention 1.18 versus 1.07; language 1.22 versus 0.91; naming 1.07 versus 0.86). Conclusions— The stronger relationship between impairment on the MoCA with hypertensive arteriopathy, independent of age, indicates a greater sensitivity for vascular-origin cognitive impairment. Use of MoCA should improve sensitivity for cognitive impairment and treatment effects in future studies.

Age-Specific Incidence, Outcome, Cost, and Projected Future Burden of Atrial Fibrillation–Related Embolic Vascular Events

Background— Prevalence of atrial fibrillation (AF) is >10% at age ≥80 years, but the impact of population aging on rates of AF-related ischemic events is uncertain. Methods and Results— We studied age-specific incidence, outcome, and cost of all AF-related incident strokes and systemic emboli from 2002 to 2012 in the Oxford Vascular Study (OXVASC). We determined time trends in incidence of AF-related stroke in comparison with a sister study in 1981 to 1986, extrapolated numbers to the UK population and projected future numbers. Of 3096 acute cerebral or peripheral vascular events in the 92 728 study population, 383 incident ischemic strokes and 71 systemic emboli were related to AF, of which 272 (59.9%) occurred at ≥80 years. Of 597 fatal or disabling incident ischemic strokes, 262 (43.9%) were AF-related. Numbers of AF-related ischemic strokes at age ≥80 years increased nearly 3-fold from 1981–1986 to 2002–2012 (extrapolated to the United Kingdom: 6621 to 18 176 per year), due partly to increased age-specific incidence (relative rate 1.52, 95% confidence interval 1.31-1.77, P=0.001), with potentially preventable AF-related events at age ≥80 years costing the United Kingdom £374 million per year. At current incidence rates, numbers of AF-related embolic events at age ≥80 years will treble again by 2050 (72 974/year), with 83.5% of all events occurring in this age group. Conclusions— Numbers of AF-related incident ischemic strokes at age ≥80 years have trebled over the last 25 years, despite the introduction of anticoagulants, and are projected to treble again by 2050, along with the numbers of systemic emboli. Improved prevention in older people with AF should be a major public health priority.

The challenges of healthcare reforms in China.

Summary China is in the process of a new round of healthcare reforms. The Chinese Government has launched ambitious healthcare reforms aiming to achieve equitable access to basic health services; and to build a safe, effective, convenient and inexpensive healthcare system for both urban and rural residents. This paper will provide a brief overview of China’s healthcare reforms, and describe the challenges and opportunities facing these reforms.

Total small vessel disease score and risk of recurrent stroke Validation in 2 large cohorts

Objective: In patients with TIA and ischemic stroke, we validated the total small vessel disease (SVD) score by determining its prognostic value for recurrent stroke. Methods: Two independent prospective studies were conducted, one comprising predominantly Caucasian patients with TIA/ischemic stroke (Oxford Vascular Study [OXVASC]) and one predominantly Chinese patients with ischemic stroke (University of Hong Kong [HKU]). Cerebral MRI was performed and assessed for lacunes, microbleeds, white matter hyperintensities (WMH), and perivascular spaces (PVS). Predictive value of total SVD score for risk of recurrent stroke was determined and potential refinements considered. Results: In 2,002 patients with TIA/ischemic stroke (OXVASC n = 1,028, HKU n = 974, 6,924 patient-years follow-up), a higher score was associated with an increased risk of recurrent ischemic stroke (adjusted hazard ratio [HR] per unit increase: 1.32, 1.16–1.51, p < 0.0001; c statistic 0.61, 0.56–0.65, p < 0.0001) and intracerebral hemorrhage (ICH) (HR 1.54, 1.11–2.13, p = 0.009; c statistic 0.65, 0.54–0.76, p = 0.006). A higher score predicted recurrent stroke in SVD and non-SVD TIA/ischemic stroke subtypes (c statistic 0.67, 0.59–0.74, p < 0.0001 and 0.60, 0.55–0.65, p < 0.0001). Including burden of microbleeds and WMH and adjusting the cutoff of basal ganglia PVS potentially improved predictive power for ICH (c statistic 0.71, 0.60–0.81, phet = 0.45), but not for recurrent ischemic stroke (c statistic 0.60, 0.56–0.65, phet = 0.76) on internal validation. Conclusions: The total SVD score has predictive value for recurrent stroke after TIA/ischemic stroke. Prediction of recurrence in patients with nonlacunar events highlights the potential role of SVD in wider stroke etiology.

Identification of missed hypertension and hypertensive arteriopathy with home versus ambulatory blood pressure measurement in patients with TIA or minor stroke

Impaired cognitive function is often reported in patients with carotid artery stenosis. Revascularization by transcervical carotid artery stenting (CAS) with flow reversal is associated with increased cognition regardless of age, asymtomatic status, previous stroke events, baseline brain parenchyma status, and contralateral carotid artery stenosis. The findings of this preliminary prospective study suggest that transcervical CAS and stenting with flow reversal for cerebral protection is a safe technique that will improve, or at least not worsen, cognitive performance.Impaired cognitive function is often reported in patients with carotid artery stenosis. Revascularization by transcervical carotid artery stenting (CAS) with flow reversal is associated with increased cognition regardless of age, asymtomatic status, previous stroke events, baseline brain parenchyma status, and contralateral carotid artery stenosis. The findings of this preliminary prospective study suggest that transcervical CAS and stenting with flow reversal for cerebral protection is a safe technique that will improve, or at least not worsen, cognitive performance.