Risk factors for incident cardiovascular events and their population attributable fractions in rural India: The Rishi Valley Prospective Cohort Study.

OBJECTIVE: We prospectively determined incident cardiovascular events and their association with risk factors in rural India. METHODS: We followed up with 7935 adults from the Rishi Valley Prospective Cohort Study to identify incident cardiovascular events. Using Cox proportional hazards regression, we estimated hazard ratios (HRs) with 95% confidence intervals (95% CI) for associations between potential risk factors and cardiovascular events. Population attributable fractions (PAFs) for risk factors were estimated using R ('averisk' package). RESULTS: Of the 4809 participants without prior cardiovascular disease, 57.7% were women and baseline mean age was 45.3 years. At follow-up (median of 4.9 years, 23,180 person-years [PYs]), 202 participants developed cardiovascular events, equating to an incidence of 8.7 cardiovascular events/1000 PYs. Incidence was greater in those with hypertension (hazard ratio [HR] [95% CI] 1.73 [1.21-2.49], adjusted PAF 18%), diabetes (1.96 [1.15-3.36], 4%) or central obesity (1.77 [1.23, 2.54], 9%) which together accounted for 31% of the PAF. Non-traditional risk factors such as night sleeping hours and number of children accounted for 16% of the PAF. CONCLUSIONS: Both traditional and non-traditional cardiovascular risk factors are important contributors to incident cardiovascular events in rural India. Interventions targeted to these factors could assist in reducing the incidence of cardiovascular events.

Cost-Effectiveness of an Individualised Management Program after Stroke: A Trial-Based Economic Evaluation.

INTRODUCTION: Evidence on the cost-effectiveness of comprehensive post-stroke programs is limited. We assessed the cost-effectiveness of an individualised management program (IMP) for stroke or transient ischaemic attack (TIA). METHODS: A cost-utility analysis alongside a randomised controlled trial with a 24-month follow-up, from both societal and health system perspectives, was conducted. Adults with stroke/TIA discharged from hospitals were randomised by primary care practice to receive either usual care (UC) or an IMP in addition to UC (intervention). An IMP included stroke-specific nurse-led education and a specialist review of care plans at baseline, 3 months, and 12 months, and telephone reviews by nurses at 6 months and 18 months. Costs were expressed in 2021 Australian dollars (AUD). Costs and quality-adjusted life years (QALYs) beyond 12 months were discounted by 5%. The probability of cost-effectiveness of the intervention was determined by quantifying 10,000 bootstrapped iterations of incremental costs and QALYs below the threshold of AUD 50,000/QALY. RESULTS: Among the 502 participants (65% male, median age 69 years), 251 (50%) were in the intervention group. From a health system perspective, the incremental cost per QALY gained was AUD 53,175 in the intervention compared to the UC group, and the intervention was cost-effective in 46.7% of iterations. From a societal perspective, the intervention was dominant in 52.7% of iterations, with mean per-person costs of AUD 49,045 and 1.352 QALYs compared to mean per-person costs of AUD 51,394 and 1.324 QALYs in the UC group. The probability of the cost-effectiveness of the intervention, from a societal perspective, was 60.5%. CONCLUSIONS: Care for people with stroke/TIA using an IMP was cost-effective from a societal perspective over 24 months. Economic evaluations of prevention programs need sufficient time horizons and consideration of costs beyond direct healthcare utilisation to demonstrate their value to society.

The Role of Daily Step Count in Determining Risk Factors for Falls.

Falls risk is often assessed without considering exposure to risk. We examined the risk factors associated with falls in those with greater and lower levels of daily step count. Falls were recorded over 12 months using bimonthly calendars in community-dwelling older people (mean age 72.0, SD 6.9). Daily step count was measured using a pedometer worn consecutively for 7 days. A cut score of <5,575.5 steps/day was used to identify people with lower step count. Negative binominal models were used to identify cognitive, medical, and sensorimotor factors associated with falls in those with higher versus lower levels of daily step count. In those with lower daily step count, poorer executive function, slower gait speed, and lower steps per day were associated with increased falls risk. In those with higher step count, only mood was associated with increased falls risk. Considering daily step count is important when assessing falls risk in older people.

Patient-reported outcome measures to evaluate postoperative quality of life in patients undergoing elective abdominal surgery: a systematic review.

PURPOSE: To appraise the measurement properties of generic patient-reported outcome measures (PROMs) measuring postoperative quality of life in adults undergoing elective abdominal surgery. METHODS: We conducted a systematic review of PROMs administered after elective abdominal surgery. We systematically searched Ovid MEDLINE, Embase, the Cumulative Index to Nursing & Allied Health Literature database, and the Cochrane Library from earliest available dates to July 24, 2021, using relevant search terms. Articles were included if they reported assessment of measurement properties of a generic PROM/s measuring postoperative quality of life in adults who had undergone elective abdominal surgery. We used the Consensus-based Standards for the selection of health status Measurement Instruments (COSMIN) Risk of Bias checklist to assess methodological quality. We synthesized the data and used the COSMIN criteria for good measurement properties and the Grading of Recommendations, Assessment, Development and Evaluations criteria to rate the certainty of evidence. RESULTS: Of 12,121 identified articles, nine articles assessing five PROMs (SF-6D, EQ-5D, SF-36, SF-12, PROMIS-10) met inclusion criteria. Measurement properties assessed included internal consistency (n = 2), construct validity (n = 5), and responsiveness (n = 8). Two PROMs had high quality evidence for a single measurement property each. The SF-6D demonstrated high quality evidence for responsiveness and the EQ-5D had high quality evidence for construct validity. CONCLUSION: There is insufficient evidence to support the choice of a specific generic PROM to evaluate quality of life following elective abdominal surgery. Clinicians and researchers should be aware of the current limitations in knowledge of the measurement properties of available PROMs.

Quality of life after stroke: a longitudinal analysis of a cluster randomized trial.

PURPOSE: Health-related quality of life (QoL) is poor after stroke, but may be improved with comprehensive care plans. We aimed to determine the effects of an individualized management program on QoL in people with stroke or transient ischemic attack (TIA), describe changes in QoL over time, and identify variables associated with QoL. METHODS: This was a multicenter, cluster randomized controlled trial with blinded assessment of outcomes and intention-to-treat analysis. Patients with stroke or TIA aged ≥ 18 years were randomized by general practice to receive usual care or an intervention comprising a tailored chronic disease management plan and education. QoL was assessed at baseline and 3, 12, and 24 months after baseline using the Assessment of Quality of Life instrument. Patient responses were converted to utility scores ranging from - 0.04 (worse than death) to 1.00 (good health). Mixed-effects models were used for analyses. RESULTS: Among 563 participants recruited (mean age 68.4 years, 64.5% male), median utility scores ranged from 0.700 to 0.772 at different time points, with no difference observed between intervention and usual care groups. QoL improved significantly from baseline to 3 months (ß = 0.019; P = 0.015) and 12 months (ß = 0.033; P < 0.001), but not from baseline to 24 months (ß = 0.013; P = 0.140) in both groups combined. Older age, females, lower educational attainment, greater handicap, anxiety and depression were longitudinally associated with poor QoL. CONCLUSION: An individualized management program did not improve QoL over 24 months. Those who are older, female, with lower educational attainment, greater anxiety, depression and handicap may require greater support. CLINICAL TRIAL REGISTRATION: https://www.anzctr.org.au . Unique identifier: ACTRN12608000166370.

The Associations Between Grey Matter Volume Covariance Patterns and Gait Variability-The Tasmanian Study of Cognition and Gait.

Greater gait variability predicts dementia. However, little is known about the neural correlates of gait variability. The aims of this study were to determine (1) grey matter volume covariance patterns associated with gait variability and (2) whether these patterns were associated with specific cognitive domains. Participants (n = 351; mean age 71.9 ± 7.1) were randomly selected from the Southern Tasmanian electoral roll. Step time, step length, step width and double support time were measured using an electronic walkway. Gait variability was calculated as the standard deviation of all steps for each gait measure. Voxel-based morphometry and multivariate covariance-based analyses were used to identify grey matter patterns associated with each gait variability measure. The individual expressions of grey matter patterns were correlated with processing speed, memory, executive and visuospatial functions. The grey matter covariance pattern of double support time variability included frontal, medial temporal, anterior cingulate, insula, cerebellar and striatal regions. Greater expression of this pattern was correlated with poorer performance in all cognitive functions (p < 0.001). The covariance pattern of step length variability included frontal, temporal, insula, occipital and cerebellar regions and was correlated with all cognitive functions (p < 0.05), except memory (p = 0.76). The covariance pattern of step width variability was limited to the cerebellum and correlated only with memory (p = 0.047). No significant pattern was identified for step time variability. In conclusion, different grey matter covariance patterns were associated with individual gait variability measures. These patterns were also correlated with specific cognitive functions, suggesting common neural networks may underlie both gait and cognition.

Effectiveness of a scalable group-based education and monitoring program, delivered by health workers, to improve control of hypertension in rural India: A cluster randomised controlled trial.

BACKGROUND: New methods are required to manage hypertension in resource-poor settings. We hypothesised that a community health worker (CHW)-led group-based education and monitoring intervention would improve control of blood pressure (BP). METHODS AND FINDINGS: We conducted a baseline community-based survey followed by a cluster randomised controlled trial of people with hypertension in 3 rural regions of South India, each at differing stages of epidemiological transition. Participants with hypertension, defined as BP ≥ 140/90 mm Hg or taking antihypertensive medication, were advised to visit a doctor. In each region, villages were randomly assigned to intervention or usual care (UC) in a 1:2 ratio. In intervention clusters, trained CHWs delivered a group-based intervention to people with hypertension. The program, conducted fortnightly for 3 months, included monitoring of BP, education about hypertension, and support for healthy lifestyle change. Outcomes were assessed approximately 2 months after completion of the intervention. The primary outcome was control of BP (BP < 140/90 mm Hg), analysed using mixed effects regression, clustered by village within region and adjusted for baseline control of hypertension (using intention-to-treat principles). Of 2,382 potentially eligible people, 637 from 5 intervention clusters and 1,097 from 10 UC clusters were recruited between November 2015 and April 2016, with follow-up occurring in 459 in the intervention group and 1,012 in UC. Mean age was 56.9 years (SD 13.7). Baseline BP was similar between groups. Control of BP improved from baseline to follow-up more in the intervention group (from 227 [49.5%] to 320 [69.7%] individuals) than in the UC group (from 528 [52.2%] to 624 [61.7%] individuals) (odds ratio [OR] 1.6, 95% CI 1.2-2.1; P = 0.001). In secondary outcome analyses, there was a greater decline in systolic BP in the intervention than UC group (-5.0 mm Hg, 95% CI -7.1 to -3.0; P < 0.001) and a greater decline in diastolic BP (-2.1 mm Hg, 95% CI -3.6 to -0.6; P < 0.006), but no detectable difference in the use of BP-lowering medications between groups (OR 1.2, 95% CI 0.8-1.9; P = 0.34). Similar results were found when using imputation analyses that included those lost to follow-up. Limitations include a relatively short follow-up period and use of outcome assessors who were not blinded to the group allocation. CONCLUSIONS: While the durability of the effect is uncertain, this trial provides evidence that a low-cost program using CHWs to deliver an education and monitoring intervention is effective in controlling BP and is potentially scalable in resource-poor settings globally. TRIAL REGISTRATION: The trial was registered with the Clinical Trials Registry-India (CTRI/2016/02/006678).

Adherence to the Australian Dietary Guidelines Is Not Associated with Brain Structure or Cognitive Function in Older Adults.

BACKGROUND: Cognitive dysfunction is common in older adults, particularly in those with type 2 diabetes (T2D). Higher adherence to the Dietary Guidelines for Americans is associated with better brain health. However, it is unclear if adherence to the Australian Dietary Guidelines (ADG) is associated with cognition or brain structure in older adults. OBJECTIVE: The aims of this study were to 1) examine the relation between adherence to the ADG, cognition, and brain MRI and 2) determine whether T2D modifies any associations. METHODS: The Cognition and Diabetes in Older Tasmanians Study is a cross-sectional study in 688 people (n = 343 with T2D) aged 55-90 y. A validated 80-item food-frequency questionnaire was used to assess dietary intake. Adherence to the 2013 ADG was estimated using the Dietary Guidelines Index (DGI). Cognitive function in multiple domains was assessed with a comprehensive battery of neuropsychological tests and brain structure with MRI. Multivariable linear models were used to assess the associations between DGI, cognitive z scores, and brain structure. Effect modification for T2D was examined with a DGI × T2D product term. RESULTS: The mean age of the sample was 69.9 y (SD: 7.4 y), with 57.1% men. The mean DGI was 54.8 (SD: 10.7; range: 24.1-84.6). No associations were observed between the Australian DGI and cognition or brain MRI measures. T2D did not modify any associations (P > 0.05). CONCLUSIONS: This is the first study to investigate associations between adherence to the ADG and brain health in the older adults with and without T2D. Future prospective studies are required to clarify if there are long-term associations.

Type 2 diabetes mellitus, brain atrophy and cognitive decline in older people: a longitudinal study.

AIMS/HYPOTHESIS: The aims of the study were to examine whether type 2 diabetes mellitus is associated with greater brain atrophy and cognitive decline, and whether brain atrophy mediates associations between type 2 diabetes and cognitive decline. METHODS: Participants without dementia aged 55-90 years from the Cognition and Diabetes in Older Tasmanians (CDOT) study underwent brain MRI (ventricular and total brain volume) and neuropsychological measures (global function and seven cognitive domains) at three time points over 4.6 years. Mixed models were used to examine longitudinal associations of type 2 diabetes with cognitive and MRI measures, adjusting for covariates. A test of mediation was used to determine whether brain atrophy explained associations between type 2 diabetes and cognitive decline. RESULTS: A total of 705 participants (diabetes: n = 348, mean age 68.2 years [SD 7.0]; no diabetes: n = 357, mean age 72.5 years [SD 7.1]) were available at baseline. Adjusting for age, sex, education and vascular risk factors, there were significant diabetes × time interactions for verbal memory (ß -0.06; 95% CI -0.09, -0.02) and verbal fluency (ß -0.03; 95% CI -0.06, -0.00). Although people with diabetes had lower brain (ß -14.273; 95% CI -21.197, -6.580) and greater ventricular (ß 2.672; 95% CI 0.152, 5.193) volumes at baseline, there were no significant diabetes × time interactions (p > 0.05) or evidence of mediation of the diabetes-cognition relationship by brain atrophy. CONCLUSIONS/INTERPRETATION: In older community-dwelling people, type 2 diabetes is associated with decline in verbal memory and fluency over ~5 years. The effect of diabetes on brain atrophy may begin earlier (midlife).

Dietary Patterns Are Not Associated with Brain Atrophy or Cerebral Small Vessel Disease in Older Adults with and without Type 2 Diabetes.

BACKGROUND: Unhealthy dietary patterns (DPs) are associated with poorer cognition, but few studies have investigated the underlying brain structural mechanisms. OBJECTIVE: We aimed to examine the relations between DPs, brain structure, and cognition in older people with and without type 2 diabetes. METHODS: This cross-sectional study consisted of a sample of people with (n = 343) and without type 2 diabetes (n = 346) aged 55-90 y. The 80-item Cancer Council of Victoria FFQ was used to assess dietary intake. Two DPs (prudent and traditional) for people with type 2 diabetes and 3 DPs (prudent, traditional, and Western) for those without type 2 diabetes were derived using principal component analysis. Neuropsychological tests assessed 6 cognitive domains. Brain MRI was performed to obtain gray, white matter, and hippocampal volumes and markers of small vessel disease (microbleeds, infarcts, and white matter hyperintensities). Multivariable linear regression was used to assess the cross-sectional associations between DPs, brain MRI, and cognitive variables. RESULTS: For those without type 2 diabetes, higher adherence to the Western DP was associated with lower gray matter volume (ß = -3.03 95% CI: -5.67, -0.38; P = 0.03). The addition of a cardiovascular risk score, mood, and physical activity weakened associations such that they were no longer significant (ß = -1.97 (95% CI: -4.68, 0.74) P = 0.15) for the Western DP. There were no significant associations for the other DPs in people with and without type 2 diabetes. CONCLUSIONS: In this cross-sectional study, DPs were not independently associated with brain structure in people with or without type 2 diabetes. Future prospective studies are needed to clarify the role of vascular risk factors on associations between DPs and brain health.

Acute or Delayed Systemic Administration of Human Amnion Epithelial Cells Improves Outcomes in Experimental Stroke.

BACKGROUND AND PURPOSE: Human amnion epithelial cells (hAECs) are nonimmunogenic, nontumorigenic, anti-inflammatory cells normally discarded with placental tissue. We reasoned that their profile of biological features, wide availability, and the lack of ethical barriers to their use could make these cells useful as a therapy in ischemic stroke. METHODS: We tested the efficacy of acute (1.5 hours) or delayed (1-3 days) poststroke intravenous injection of hAECs in 4 established animal models of cerebral ischemia. Animals included young (7-14 weeks) and aged mice (20-22 months) of both sexes, as well as adult marmosets of either sex. RESULTS: We found that hAECs administered 1.5 hours after stroke in mice migrated to the ischemic brain via a CXC chemokine receptor type 4-dependent mechanism and reduced brain inflammation, infarct development, and functional deficits. Furthermore, if hAECs administration was delayed until 1 or 3 days poststroke, long-term functional recovery was still augmented in young and aged mice of both sexes. We also showed proof-of-principle evidence in marmosets that acute intravenous injection of hAECs prevented infarct development from day 1 to day 10 after stroke. CONCLUSIONS: Systemic poststroke administration of hAECs elicits marked neuroprotection and facilitates mechanisms of repair and recovery.

Influence of blood pressure level and age on within-visit blood pressure variability in children and adolescents.

Blood pressure (BP) is variable in children and this could affect BP assessment, but the magnitude of within-visit BP variability (BPV) over consecutive measurements has never been investigated. This study aimed to determine the direction and magnitude of, and factors affecting, within-visit BPV in children and adolescents. BP was recorded among 3047 children (aged 12 years [95%CI 12, 13], males 52%) from the 2011-2013 Australian Health Survey. BPV was defined as the absolute difference (∆SBPABS) between the first (SBP1) and second systolic BP (SBP2) and the overall variability in three measures when available (SBPV). On average, ∆SBPABS was 6.7 mmHg (95%CI 6.3, 7.0) and SBPV was 8.2% (95%CI 7.8, 8.6). ∆SBPABS was greater with higher BP levels but lower with older age. From first to second measurements, SBP decreased in 58% (95%CI 56, 60), did not change in 10% (95%CI 9, 12), and increased in 32% (95%CI 29, 34) of the population. CONCLUSIONS: BP is highly variable in children and adolescents, with the magnitude of variability being associated with both age and BP level. SBP increases on repeat measurement in a substantial proportion of the population. The optimal protocol of BP assessment to address this increased BPV needs to be determined. What is Known: • Diagnosis of elevated blood pressure (BP) is based on strict probabilistic criteria, the difference between the 90th (pre-hypertension) and 95th (hypertension) percentiles only being 3-4 mmHg. • BP variability could affect BP classification among children and adolescents. What is New: • The magnitude of BP change among children and adolescents is highly affected by BP level and age. • BP does not always drop on consecutive measurements, and evidence-based BP assessment protocols should be established to avoid misdiagnosis of hypertension.

Community-Based Intervention to Improve Cardiometabolic Targets in Patients With Stroke: A Randomized Controlled Trial.

BACKGROUND AND PURPOSE: Many guidelines for secondary prevention of stroke focus on controlling cardiometabolic risk factors. We investigated the effectiveness of a management program for attaining cardiometabolic targets in survivors of stroke/transient ischemic attack. METHODS: Randomized controlled trial of survivors of stroke/transient ischemic attack aged ≥18 years. General practices were randomized to usual care (control) or an intervention comprising specialist review of care plans and nurse education in addition to usual care. The outcome is attainment of pre-defined cardiometabolic targets based on Australian guidelines. Multivariable regression was undertaken to determine efficacy and identify factors associated with attaining targets. RESULTS: Overall, 283 subjects were randomized to the intervention and 280 to controls. Although we found no between-group difference in overall cardiometabolic targets achieved at 12 months, the intervention group more often achieved control of low-density lipoprotein cholesterol (odds ratio, 1.97; 95% confidence interval, 1.18-3.29) than controls. At 24 months, no between-group differences were observed. Medication adherence was ≥80% at follow-up, but uptake of lifestyle/behavioral habits was poor. Older age, being male, being married/living with partner, and having greater functional ability or a history of diabetes mellitus were associated with attaining targets. CONCLUSIONS: The intervention in this largely negative trial only had a detectable effect on attaining target for lipids but not for other factors at 12 months or any factor at 24 months. This limited effect may be attributable to inadequate uptake of behavioral/lifestyle interventions, highlighting the need for new or better approaches to achieve meaningful behavioral change. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: ACTRN12608000166370.

Effectiveness of an Intervention to Improve Risk Factor Knowledge in Patients With Stroke: A Randomized Controlled Trial.

BACKGROUND AND PURPOSE: Despite the benefit of risk awareness in secondary prevention, survivors of stroke are often unaware of their risk factors. We determined whether a nurse-led intervention improved knowledge of risk factors in people with stroke or transient ischemic attack. METHODS: Prospective study nested within a randomized controlled trial of risk factor management in survivors of stroke or transient ischemic attack. INTERVENTION: 3 nurse education visits and specialist review of care plans. OUTCOME: unprompted knowledge of risk factors of stroke or transient ischemic attack at 24 months. Effect of intervention on knowledge and factors associated with knowledge were determined using multivariable regression models. RESULTS: Knowledge was assessed in 268 consecutive participants from the main trial, 128 in usual care and 140 in the intervention. Overall, 34% of participants were unable to name any risk factor. In adjusted analyses, the intervention group had better overall knowledge than controls (incidence risk ratio, 1.26; 95% confidence interval, 1.00-1.58). Greater functional ability and polypharmacy were associated with better knowledge and older age and having more comorbidities associated with poorer knowledge. CONCLUSIONS: Overall knowledge of risk factors of stroke or transient ischemic attack was better in the intervention group than controls. However, knowledge was generally poor. New and more effective strategies are required, especially in subgroups identified as having poor knowledge. CLINICAL TRIAL REGISTRATION: URL: http://www.anzctr.org.au. Unique identifier: ACTRN12608000166370.

Maximizing Patient Recruitment and Retention in a Secondary Stroke Prevention Clinical Trial: Lessons Learned from the STAND FIRM Study.

BACKGROUND: Recruitment and retention of patients in a clinical trial is important for generalizability and robustness of findings. We aimed to investigate features of a study design that were associated with recruitment and retention in a Phase II and Phase III trial of a secondary prevention program for stroke. METHODS: Following informed consent in hospital, Phase II participants were randomized to intervention or usual care. Baseline clinical assessments were conducted at home approximately 3 months after discharge. In Phase III study, informed consent was obtained at home. We compared the characteristics of participants recruited and retained to 12 months for both phases. Interviews with study nurses were undertaken in order to ascertain their opinions of features of study design. Triangulation was used to identify the features of study design that nurses thought had improved recruitment and retention. RESULTS: All 24 eligible participants were recruited to the Phase II pilot study (100% recruitment), with 67% retention at 12 months. In Phase III study, 570 participants were recruited, and 93% of these participants had reached their 12-month assessment (n = 532) and were still participating. Consistent with the greater patient retention in Phase III study, nurses reported that patients' willingness to participate was greater when consent was obtained at home. CONCLUSION: Following a change in the consent process from hospital to home, more participants continued participation to 12 months. Pilot studies can provide important data to improve study design and better understand potential barriers to recruitment and retention.

Trends over time in the risk of stroke after an incident transient ischemic attack.

BACKGROUND AND PURPOSE: Long-term population trends in the early risk of stroke after transient ischemic attack (TIA) are unknown. We hypothesized that there has been an appreciable decline in the risk of stroke after TIA for the last decade. METHODS: Population-level cohort study from Victoria, Australia (population 5.6 million), using linked data from hospitals, emergency departments, and death records (2001-2011), with a 2-year clearance period to define incident TIAs. Age-specific rates/1000, yearly incident rate ratios, and age-sex-adjusted risk of stroke after TIA were computed. RESULTS: The mean age of 46 971 patients with TIA was 71 (SD=15), 52% women. In patients ≥65 years, annual TIA rates declined between 2001 and 2011 from 5.8 to 4.8/1000 (men) and from 5.3 to 4.2/1000 (women). Yearly incident rate ratios were 0.97 (95% confidence interval, 0.96-0.98) in men and 0.97 (95% confidence interval, 0.97-0.98) in women. Overall, the 90-day stroke risk was 3.1%. Age-sex-adjusted risk of stroke at 90 days after a TIA decreased by 3% per year (odds ratio for the effect of year, 0.97; 95% confidence interval, 0.95-0.99). Male sex, direct discharge from emergency departments, public hospital care, stroke unit care, and absence of vascular risk factors were associated with a downward yearly trend of stroke within 90 days of TIA. CONCLUSIONS: Over the last 10 years, there has been a measurable decline in the 90-day risk of stroke after an incident TIA and overall decline in rates of TIA in Victoria, Australia. These trends may reflect improved primary and secondary prevention efforts for the last decade.

Comparison of the performance of cardiovascular risk prediction tools in rural India: the Rishi Valley Prospective Cohort Study.

AIMS: We compared the performance of cardiovascular risk prediction tools in rural India. METHODS AND RESULTS: We applied the World Health Organization Risk Score (WHO-RS) tools, Australian Risk Score (ARS), and Global risk (Globorisk) prediction tools to participants aged 40-74 years, without prior cardiovascular disease, in the Rishi Valley Prospective Cohort Study, Andhra Pradesh, India. Cardiovascular events during the 5-year follow-up period were identified by verbal autopsy (fatal events) or self-report (non-fatal events). The predictive performance of each tool was assessed by discrimination and calibration. Sensitivity and specificity of each tool for identifying high-risk individuals were assessed using a risk score cut-off of 10% alone or this 10% cut-off plus clinical risk criteria of diabetes in those aged >60 years, high blood pressure, or high cholesterol. Among 2333 participants (10 731 person-years of follow-up), 102 participants developed a cardiovascular event. The 5-year observed risk was 4.4% (95% confidence interval: 3.6-5.3). The WHO-RS tools underestimated cardiovascular risk but the ARS overestimated risk, particularly in men. Both the laboratory-based (C-statistic: 0.68 and χ2: 26.5, P = 0.003) and non-laboratory-based (C-statistic: 0.69 and χ2: 20.29, P = 0.003) Globorisk tools showed relatively good discrimination and agreement. Addition of clinical criteria to a 10% risk score cut-off improved the diagnostic accuracy of all tools. CONCLUSION: Cardiovascular risk prediction tools performed disparately in a setting of disadvantage in rural India, with the Globorisk performing best. Addition of clinical criteria to a 10% risk score cut-off aids assessment of risk of a cardiovascular event in rural India. LAY SUMMARY: In a cohort of people without prior cardiovascular disease, tools used to predict the risk of cardiovascular events varied widely in their ability to accurately predict who would develop a cardiovascular event.The Globorisk, and to a lesser extent the ARS, tools could be appropriate for this setting in rural India.Adding clinical criteria, such as sustained high blood pressure, to a cut-off of 10% risk of a cardiovascular event within 5 years could improve identification of individuals who should be monitored closely and provided with appropriate preventive medications.

Clinical Associations and Prognostic Value of MRI-Visible Perivascular Spaces in Patients With Ischemic Stroke or TIA: A Pooled Analysis

BACKGROUND AND OBJECTIVES: Visible perivascular spaces are an MRI marker of cerebral small vessel disease and might predict future stroke. However, results from existing studies vary. We aimed to clarify this through a large collaborative multicenter analysis. METHODS: We pooled individual patient data from a consortium of prospective cohort studies. Participants had recent ischemic stroke or transient ischemic attack (TIA), underwent baseline MRI, and were followed up for ischemic stroke and symptomatic intracranial hemorrhage (ICH). Perivascular spaces in the basal ganglia (BGPVS) and perivascular spaces in the centrum semiovale (CSOPVS) were rated locally using a validated visual scale. We investigated clinical and radiologic associations cross-sectionally using multinomial logistic regression and prospective associations with ischemic stroke and ICH using Cox regression. RESULTS: We included 7,778 participants (mean age 70.6 years; 42.7% female) from 16 studies, followed up for a median of 1.44 years. Eighty ICH and 424 ischemic strokes occurred. BGPVS were associated with increasing age, hypertension, previous ischemic stroke, previous ICH, lacunes, cerebral microbleeds, and white matter hyperintensities. CSOPVS showed consistently weaker associations. Prospectively, after adjusting for potential confounders including cerebral microbleeds, increasing BGPVS burden was independently associated with future ischemic stroke (versus 0-10 BGPVS, 11-20 BGPVS: HR 1.19, 95% CI 0.93-1.53; 21+ BGPVS: HR 1.50, 95% CI 1.10-2.06; p = 0.040). Higher BGPVS burden was associated with increased ICH risk in univariable analysis, but not in adjusted analyses. CSOPVS were not significantly associated with either outcome. DISCUSSION: In patients with ischemic stroke or TIA, increasing BGPVS burden is associated with more severe cerebral small vessel disease and higher ischemic stroke risk. Neither BGPVS nor CSOPVS were independently associated with future ICH.

Statin Therapy for Secondary Prevention in Ischemic Stroke Patients With Cerebral Microbleeds.

BACKGROUND AND OBJECTIVES: The association between statin use and the risk of intracranial hemorrhage (ICrH) following ischemic stroke (IS) or transient ischemic attack (TIA) in patients with cerebral microbleeds (CMBs) remains uncertain. This study investigated the risk of recurrent IS and ICrH in patients receiving statins based on the presence of CMBs. METHODS: We conducted a pooled analysis of individual patient data from the Microbleeds International Collaborative Network, comprising 32 hospital-based prospective studies fulfilling the following criteria: adult patients with IS or TIA, availability of appropriate baseline MRI for CMB quantification and distribution, registration of statin use after the index stroke, and collection of stroke event data during a follow-up period of ≥3 months. The primary endpoint was the occurrence of recurrent symptomatic stroke (IS or ICrH), while secondary endpoints included IS alone or ICrH alone. We calculated incidence rates and performed Cox regression analyses adjusting for age, sex, hypertension, atrial fibrillation, previous stroke, and use of antiplatelet or anticoagulant drugs to explore the association between statin use and stroke events during follow-up in patients with CMBs. RESULTS: In total, 16,373 patients were included (mean age 70.5 ± 12.8 years; 42.5% female). Among them, 10,812 received statins at discharge, and 4,668 had 1 or more CMBs. The median follow-up duration was 1.34 years (interquartile range: 0.32-2.44). In patients with CMBs, statin users were compared with nonusers. Compared with nonusers, statin therapy was associated with a reduced risk of any stroke (incidence rate [IR] 53 vs 79 per 1,000 patient-years, adjusted hazard ratio [aHR] 0.68 [95% CI 0.56-0.84]), a reduced risk of IS (IR 39 vs 65 per 1,000 patient-years, aHR 0.65 [95% CI 0.51-0.82]), and no association with the risk of ICrH (IR 11 vs 16 per 1,000 patient-years, aHR 0.73 [95% CI 0.46-1.15]). The results in aHR remained consistent when considering anatomical distribution and high burden (≥5) of CMBs. DISCUSSION: These observational data suggest that secondary stroke prevention with statins in patients with IS or TIA and CMBs is associated with a lower risk of any stroke or IS without an increased risk of ICrH. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with IS or TIA and CMBs, statins lower the risk of any stroke or IS without increasing the risk of ICrH.

Effect of alteplase, benzodiazepines and beta-blocker on post-stroke pneumonia: Exploration of VISTA-Acute.

BACKGROUND: Post-stroke pneumonia is a frequent complication of stroke and is associated with high mortality. Investigators have described its associations with beta-blocker. However, there has been no evaluation of the role of recombinant tissue plasminogen activator (RTPA). We postulate that RTPA may modify the effect of stroke on pneumonia by reducing stroke disability. We explore this using data from neuroprotection trials in Virtual International Stroke Trials Archive (VISTA)-Acute. METHOD: We evaluated the impact of RTPA and other medications in random forest model. Random forest is a type of supervised ensemble tree-based machine learning method. We used the standard approach for performing random forest and partitioned the data into training (70%) and validation (30%) sets. This action enabled to the model developed on training data to be evaluated in the validation data. We borrowed idea from Coalition Game Theory on fair distribution of marginal profit (Shapley value) to determine proportional contribution of a covariate to the model. Consistent with other analysis using the VISTA-Acute data, the diagnosis of post-stroke pneumonia was based on reports of serious adverse events. RESULTS: The overall frequency of pneumonia was 10.9% (614/5652). It was present in 11.5% of the RTPA (270/2358) and 10.4% (344/3295) of the no RTPA groups. There was significant (p<0.05) imbalance in covariates (age, baseline National Institutes of Health Stroke Scale (NIHSS), diabetes, and sex). The AUC for training data was 0.70 (95% CI 0.65-0.76), validation data was 0.67 (95% CI 0.62-0.73). The Shapley value shows that baseline NIHSS (≥10) and age (≥80) made the largest contribution to the model of pneumonia while absence of benzodiazepine may protect against pneumonia. RTPA and beta-blocker had very low effect on frequency of pneumonia. CONCLUSION: In this cohort pneumonia was strongly associated with stroke severity and age whereas RTPA had a much lower effect. An intriguing finding is a possible association between benzodiazepine and pneumonia but this requires further evaluation.