Systematic Review and Meta-Analysis of Prehospital Machine Learning Scores as Screening Tools for Early Detection of Large Vessel Occlusion in Patients With Suspected Stroke.

BACKGROUND: Enhanced detection of large vessel occlusion (LVO) through machine learning (ML) for acute ischemic stroke appears promising. This systematic review explored the capabilities of ML models compared with prehospital stroke scales for LVO prediction. METHODS AND RESULTS: Six bibliographic databases were searched from inception until October 10, 2023. Meta-analyses pooled the model performance using area under the curve (AUC), sensitivity, specificity, and summary receiver operating characteristic curve. Of 1544 studies screened, 8 retrospective studies were eligible, including 32 prehospital stroke scales and 21 ML models. Of the 9 prehospital scales meta-analyzed, the Rapid Arterial Occlusion Evaluation had the highest pooled AUC (0.82 [95% CI, 0.79-0.84]). Support Vector Machine achieved the highest AUC of 9 ML models included (pooled AUC, 0.89 [95% CI, 0.88-0.89]). Six prehospital stroke scales and 10 ML models were eligible for summary receiver operating characteristic analysis. Pooled sensitivity and specificity for any prehospital stroke scale were 0.72 (95% CI, 0.68-0.75) and 0.77 (95% CI, 0.72-0.81), respectively; summary receiver operating characteristic curve AUC was 0.80 (95% CI, 0.76-0.83). Pooled sensitivity for any ML model for LVO was 0.73 (95% CI, 0.64-0.79), specificity was 0.85 (95% CI, 0.80-0.89), and summary receiver operating characteristic curve AUC was 0.87 (95% CI, 0.83-0.89). CONCLUSIONS: Both prehospital stroke scales and ML models demonstrated varying accuracies in predicting LVO. Despite ML potential for improved LVO detection in the prehospital setting, application remains limited by the absence of prospective external validation, limited sample sizes, and lack of real-world performance data in a prehospital setting.

Hospitalisations and emergency department presentations by older individuals accessing long-term aged care in Australia.

Objective The study examined emergency department (ED) presentations, unplanned hospitalisations and potentially preventable hospitalisations in older people receiving long-term care by type of care received (i.e. permanent residential aged care or home care packages in the community), in Australia in 2019. Methods A retrospective cohort study was conducted using the Registry of Senior Australians National Historical Cohort. Individuals were included if they resided in South Australia, Queensland, Victoria or New South Wales, received a home care package or permanent residential aged care in 2019 and were aged ≥65 years. The cumulative incidence of ED presentations, unplanned hospitalisations and potentially preventable hospitalisations in each of the long-term care service types were estimated during the year. Days in hospital per 1000 individuals were also calculated. Results The study included 203,278 individuals accessing permanent residential aged care (209,639 episodes) and 118,999 accessing home care packages in the community (127,893 episodes). A higher proportion of people accessing home care packages had an ED presentation (43.1% [95% confidence interval, 42.8-43.3], vs 37.8% [37.6-38.0]), unplanned hospitalisation (39.8% [39.6-40.1] vs 33.4% [33.2-33.6]) and potentially preventable hospitalisation (11.8% [11.6-12.0] vs 8.2% [8.1-8.4]) than people accessing permanent residential aged care. Individuals with home care packages had more days in hospital due to unplanned hospitalisations than those in residential care (7745 vs 3049 days/1000 individuals). Conclusions While a high proportion of older people in long-term care have ED presentations, unplanned hospitalisations and potentially preventable hospitalisations, people in the community with home care packages experience these events at a higher frequency.

Adherence to the Atrial fibrillation Better Care pathway and the risk of adverse health outcomes in older care home residents with atrial fibrillation: a retrospective data linkage study 2003-18.

BACKGROUND: The Atrial fibrillation Better Care (ABC) pathway is the gold-standard approach to atrial fibrillation (AF) management, but the effect of implementation on health outcomes in care home residents is unknown. OBJECTIVE: To examine associations between ABC pathway adherence and stroke, transient ischaemic attack, cardiovascular hospitalisation, major bleeding, mortality and a composite of all these outcomes in care home residents. METHODS: A retrospective cohort study of older care home residents (≥65 years) in Wales with AF was conducted between 1 January 2003 and 31 December 2018 using the Secure Anonymised Information Linkage Databank. Adherence to the ABC pathway was assessed at care home entry using pre-specified definitions. Cox proportional hazard and competing risk models were used to estimate the risk of health outcomes according to ABC adherence. RESULTS: From 14,493 residents (median [interquartile range] age 87.0 [82.6-91.2] years, 35.2% male) with AF, 5,531 (38.2%) were ABC pathway adherent. Pathway adherence was not significantly associated with risk of the composite outcome (adjusted hazard ratio, 95% confidence interval [CI]: 1.01 [0.97-1.05]). There was a significant independent association observed between ABC pathway adherence and a reduced risk of myocardial infarction (0.70 [0.50-0.98]), but a higher risk of haemorrhagic stroke (1.59 [1.06-2.39]). ABC pathway adherence was not significantly associated with any other individual health outcomes examined. CONCLUSION: An ABC adherent approach in care home residents was not consistently associated with improved health outcomes. Findings should be interpreted with caution owing to difficulties in defining pathway adherence using routinely collected data and an individualised approach is recommended.

Subclinical thyroid dysfunction and the risk of incident atrial fibrillation: A systematic review and meta-analysis.

BACKGROUND: Thyroid hormones act on the cardiovascular system directly by modulating its function and indirectly by transcriptional regulation of gene expression in the heart and the vasculature. Studies have shown associations between overt and subclinical thyroid disorders and cardiovascular outcomes. The aim of this study was to perform a systematic review and meta-analysis to assess the potential relationships between subclinical hyper- and hypothyroidism and risk of atrial fibrillation (AF), and post-operative AF. METHODS: MEDLINE and Scopus databases were searched from inception to 18th February 2023 for randomised controlled trials, case-control studies, and cohort studies which assessed the relationship between subclinical thyroid dysfunction and incident AF events. Risk of bias and the quality of evidence were assessed using the RoBANS tool and GRADE approach, respectively. Meta-analysis was conducted in Review Manager 5.4 using the Mantel-Haenszel statistical method and a random-effects model. Data are presented as risk ratios with 95% confidence intervals. Statistical heterogeneity amongst studies was assessed by the chi-squared (χ2) test and I2 statistic. p≤0.05 were considered significant. RESULTS: A total of 6467 records were identified, of which 10 cohort studies met the inclusion criteria. Both subclinical hyperthyroidism and subclinical hypothyroidism were associated with an increased risk of incident AF (risk ratio (RR), 1.99; 95% confidence interval (CI), 1.43-2.77; n = 5 studies; p<0.0001 and RR, 1.19; CI, 1.03-1.39; n = 7 studies; p = 0.02, respectively). Subgroup analysis for post-operative AF revealed marked heterogeneity between studies (I2 = 84%) and association with subclinical hypothyroidism was not significant (RR, 1.41; CI, 0.89-2.22; n = 3 studies; p = 0.15). CONCLUSIONS: The current evidence suggests that both subclinical hyperthyroidism and subclinical hypothyroidism are associated with increased risk of incident AF. Further investigation is required to determine potential causal links that would guide future clinical practice.

Direct oral anticoagulants are associated with lower risk of dementia in patients with atrial fibrillation.

BACKGROUND AND AIM: Atrial fibrillation (AF) is associated with increased risk of dementia. Whether direct oral anticoagulation (DOAC) reduce this risk compared to vitamin-K antagonist (VKA) is unclear. The aim of this study was to assess the risk of new all-cause dementia and vascular dementia in AF patients, treated with either DOAC or VKAs. METHODS: Anonymized electronic medical records from the TriNetX federated research network were used. AF patients treated with DOACs within 1 month of AF diagnosis, were 1:1 propensity score-matched with those treated with a VKA. The analysis included patients who completed 5 and 10 years of follow-up and were assessed for all-cause dementia and vascular dementia. Cox proportional hazard models were used to hazard ratios (HR), respectively with 95% confidence intervals (CIs). RESULTS: Among patients who completed 5 years of follow-up, after propensity score matching the final cohort consisted of 215,404 well-matched AF patients. All-cause dementia was diagnosed in 4,153 (3.9%) patients among those treated with DOACs and 4,150 (3.9%) among the VKA-treated patients (HR: 1.01, 95%CI: 0.96-1.05). Among patients 65-74 years old who were followed, DOAC treatment was associated with lower risk of dementia compared to VKAs (HR: 0.72; 95%CI: 0.59-0.86). Among patients who completed 10 years of follow-up, after propensity score matching the final cohort consisted of 19,208 well-matched AF patients. All-cause dementia was diagnosed in 314 (3.3%) patients among those treated with DOACs and 451 (4.7%) among the VKA-treated patients. DOAC treatment was associated with significantly lower risk of all-cause dementia during a follow-up period of 10 years compared to VKA treatment (HR: 0.72, 95%CI: 0.62-0.83), which remained consistent in patiens ≥65 years old. CONCLUSION: This propensity-score matched analysis showed that among AF patients, treatment with a DOACs for a period of 10 years was associated with lower risk of all-cause dementia and vascular dementia compared to VKA treatment, an effect which was not apparent in those treated for shorter duration. This finding requires confirmation in ongoing randomised controlled trials.

Exercised-based cardiac rehabilitation associates with lower all-cause mortality in patients with primary pulmonary hypertension.

Background: Despite pharmacological therapies to improve outcomes of pulmonary hypertension (PH), poor long-term survival remains. Exercised-based cardiac rehabilitation (ExCR) may be an alternative strategy to improve prognosis. Therefore, using an electronic medical record (EMR) database, the objective of this study was to compare mortality between patients with primary PH with ExCR vs. propensity-matched PH patients without ExCR. Methods: The retrospective analysis was conducted on February 15, 2023 using anonymized data within TriNetX, a global federated health research network. All patients were aged ≥18 years with primary PH recorded in EMRs with at least 1-year follow-up from ExCR. Using logistic regression models, patients with PH with an EMR of ExCR were 1:1 propensity score-matched with PH patients without ExCR for age, sex, race, and comorbidities, and cardiovascular care. Results: In total, 109,736 patients with primary PH met the inclusion criteria for the control group and 784 patients with primary PH met the inclusion criteria for the ExCR cohort. Using the propensity score-matched cohorts, 1-year mortality from ExCR was proportionally lower with 13.6% (n = 101 of 744 patients) in the ExCR cohort compared to 23.3% (n = 174 of 747 patients) in the controls (OR 0.52, 95% CI 0.40-0.68). Conclusion: The present study of 1,514 patients with primary PH suggests that ExCR is associated with 48% lower odds of 1-year mortality, when compared to propensity score-matched patients without ExCR.

Use of telemonitoring in patient self-management of chronic disease: a qualitative meta-synthesis.

BACKGROUND: Telemonitoring for the remote patient self-management of chronic conditions can be a cost-effective method for delivering care in chronic disease; nonetheless, its implementation in clinical practice remains low. The aim of this meta-synthesis is to explore barriers and facilitators associated with the use of remote patient monitoring of chronic disease, drawing on qualitative research, and assessing participant interactions with this technology. METHOD: A meta-synthesis of qualitative studies was performed. MEDLINE, SCOPUS and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched from database date of inception to 5 February 2021. The Critical Appraisal Skills Programme (CASP) was used to critically appraise each study. Thematic synthesis was performed to identify user (patients, carers and healthcare professionals) perspectives and experiences of patient remote monitoring of chronic disease (Type 2 diabetes mellitus, chronic obstructive pulmonary disease, and cardiovascular disease). RESULTS: Searches returned 10,401 studies and following independent screening by two reviewers, nine studies were included in this meta-synthesis. Data were synthesised and categorised into four key themes: (1) Improved care; (2) Communication; (3) Technology feasibility & acceptability; and (4) Intervention concerns. Most patients using patient remote devices felt motivated in managing their own lifestyles and felt reassured by the close monitoring and increased communication. Barriers identified involved generational differences and difficulties with the technology used. CONCLUSION: Most studies showed a positive attitude to telemonitoring, with patients preferring the convenience of telemonitoring in comparison to attending regular clinics. Further research is required to assess the most effective technology for chronic disease management, how to maintain long-term patient adherence, and identify effective approaches to address generational variation in telemonitoring up-take.

Catheter ablation and lower risk of incident dementia and mortality in older adults with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) has consistently been associated with a higher risk of incident dementia. Observational evidence has suggested catheter ablation may be associated with a lower risk of dementia in patients with AF, but further research is needed. The objectives of this study were to use a global health research network to examine associations between catheter ablation, incident dementia and mortality in older adults with AF, and amongst subgroups by age, sex, co-morbidity status, and oral anticoagulant use. METHODS: The research network primarily included healthcare organizations in the United States. This network was searched on 28th September 2022 for patients aged ≥65 years with a diagnosis of AF received at least 5 years prior to the search date. Cox proportional hazard models were run on propensity-score matched cohorts. RESULTS: After propensity score matching, 20,746 participants (mean age 68 years; 59% male) were included in each cohort with and without catheter ablation. The cohorts were well balanced for age, sex, ethnicity, co-morbidities, and cardiovascular medications received. The risk of dementia was significantly lower in the catheter ablation cohort (Hazard Ratio 0.52, 95% confidence interval: 0.45-0.61). The catheter ablation cohort also had a lower risk of all-cause mortality (Hazard Ratio 0.58, 95% confidence interval: 0.55-0.61). These associations remained in subgroup analyses in individuals aged 65-79 years, ≥80 years, males, females, participants who received OACs during follow-up, participants with paroxysmal and non-paroxysmal AF, and participants with and without hypertension, diabetes mellitus, ischemic stroke, chronic kidney disease and heart failure, including heart failure with preserved ejection fraction and heart failure with reduced ejection fraction. CONCLUSION: The observed lower risk of dementia and mortality with catheter ablation could be an important consideration when determining appropriate patient-centered rhythm control strategies for patients with AF. Further studies including data on the success of ablation are required.

Risk of myocardial infarction and ischemic stroke in individuals with first-diagnosed paroxysmal vs. non-paroxysmal atrial fibrillation under anticoagulation.

AIMS: There is conflicting evidence on whether the type of atrial fibrillation (AF) is associated with risk of cardiovascular events, including acute myocardial infarction (MI) and ischemic stroke. The aim of the present study was to investigate whether the risk of MI and ischemic stroke differs between individuals with first-diagnosed paroxysmal vs. non-paroxysmal AF treated with anticoagulants. METHODS AND RESULTS: De-identified electronic medical records from the TriNetX federated research network were used. Individuals with a new diagnosis of paroxysmal AF who had no evidence of other types of AF in their records were 1:1 propensity score-matched with individuals with non-paroxysmal AF, defined as persistent or chronic AF, who had no evidence of other types of AF in their records. All patients were followed for three years for the outcomes of MI and ischemic stroke. Cox proportional hazard models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). In the propensity-matched cohort, among 24 848 well-matched AF individuals [mean age 74.4 ± 10.4; 10 101 (40.6%) female], 410 (1.7%) were diagnosed with acute MI and 875 (3.5%) with ischemic stroke during the three-year follow-up. Individuals with paroxysmal AF had significantly higher risk of acute MI (HR: 1.65, 95%CI: 1.35-2.01) compared to those with non-paroxysmal AF. First diagnosed paroxysmal AF was associated with higher risk of non-ST elevation MI (nSTEMI) (HR: 1.89, 95%CI: 1.44-2.46). No significant association was observed between the type of AF and risk of ischemic stroke (HR: 1.09, 95%CI: 0.95-1.25). CONCLUSION: Patients with first-diagnosed paroxysmal AF had higher risk of acute MI compared to individuals with non-paroxysmal AF, attributed to the higher risk of nSTEMI among patients with first-diagnosed paroxysmal AF. There was no significant association between type of AF and risk of ischemic stroke.

Interactions Between HR-pQCT Bone Density and D3 Cr Muscle Mass (or HR-pQCT Bone Structure and HR-pQCT Muscle Density) in Predicting Fractures: The Osteoporotic Fractures in Men Study.

We examined if an interaction exists between bone and muscle in predicting fractures in older men. Prospective data from the Osteoporotic Fractures in Men study was used to build Cox proportional hazards models. Predictors included HR-pQCT total volumetric BMD (Tt.BMD), trabecular BMD (Tb.BMD), cortical BMD (Ct.BMD) and cortical area (Ct.Ar) at distal radius/tibia, HR-pQCT muscle volume and density (diaphyseal tibia), D3 -creatine dilution (D3 Cr) muscle mass, and grip strength and leg force, analyzed as continuous variables and as quartiles. Incident fractures were self-reported every 4 months via questionnaires and centrally adjudicated by physician review of radiology reports. Potential confounders (demographics, comorbidities, lifestyle factors, etc.) were considered. A total of 1353 men (mean age 84.2 ± 4.0 years, 92.7% white) were followed for 6.03 ± 2.11 years. In the unadjusted (continuous) model, there were no interactions (p > 0.05) between any muscle variable (D3 Cr muscle mass, muscle volume, muscle density, grip strength or leg force) and Tt.BMD at distal radius/tibia for fractures (all: n = 182-302; nonvertebral: n = 149-254; vertebral: n = 27-45). No consistent interactions were observed when interchanging Tt.BMD for Tb.BMD/Ct.BMD or for Ct.Ar (bone structure) at the distal radius/tibia in the unadjusted (continuous) models. Compared with men in quartiles (Q) 2-4 of D3 Cr muscle mass and Q2-4 of distal tibia Tt.BMD, men in Q1 of both had increased risk for all fractures (hazard ratio (HR) = 2.00; 95% confidence interval [CI] 1.24-3.23, p = 0.005) and nonvertebral fractures (HR = 2.10; 95% CI 1.25-3.52, p < 0.001) in the multivariable-adjusted model. Confidence intervals overlapped (p > 0.05) when visually inspecting other quartile groups in the multivariable-adjusted model. In this prospective cohort study of older men, there was no consistent interactions between bone and muscle variables on fracture risk. Larger sample sizes and longer follow-up may be needed to clarify if there is an interaction between bone and muscle on fracture risk in men. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Cerebrovascular, Cognitive and Cardiac Benefits of SGLT2 Inhibitors Therapy in Patients with Atrial Fibrillation and Type 2 Diabetes Mellitus: Results from a Global Federated Health Network Analysis.

BACKGROUND: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are effective anti-diabetic drugs improving cardiovascular outcomes in type 2 diabetes mellitus (T2DM) patients. This study investigated cardiovascular, cerebrovascular and cognitive outcomes of SGLT2i therapy in patients with atrial fibrillation (AF) and T2DM. METHODS: Observational study using TriNetX, a global health research network of anonymised electronic medical records from real-world patients between January 2018 and December 2019. The network includes healthcare organisations globally but predominately in the United States. AF patients (ICD-10-CM code: I48) with T2DM were divided according to SGLT2i use or not, and balanced using propensity score matching (PSM). Patients were followed-up for 3-years. The primary endpoints were ischaemic stroke/transient ischemic attack (TIA), intracranial haemorrhage (ICH), and incident dementia. Secondary endpoints were incident heart failure and mortality. RESULTS: We identified 89,356 AF patients with T2DM of which 5061 (5.7%) were taking a SGLT2i. After PSM, 5049 patients (mean age 66.7 ± 10.6 years; 28.9% female) were included in each group. At 3-years follow-up, the risk of ischaemic stroke/TIA was higher in patients not receiving SGLT2i (HR 1.12, 95% CI 1.01-1.24) and for ICH (HR 1.57, 95% CI 1.25-1.99) and incident dementia (HR 1.66, 95% CI 1.30-2.12). Incident heart failure (HR 1.50, 95% CI 1.34-1.68) and mortality (HR 1.77, 95% CI 1.58-1.99) risks were increased in AF patients not receiving SGLT2i. CONCLUSIONS: In our large 'real world' analysis of patients with concomitant AF and T2DM, SGLT2i reduced the risk of cerebrovascular events, incident dementia, heart failure and death.

Clinical implications of different types of dementia in patients with atrial fibrillation: Insights from a global federated health network analysis.

BACKGROUND: Atrial fibrillation (AF) associates with higher Alzheimer's disease (AD) and vascular dementia risks but the clinical implications have been scarcely investigated. We examined the association between AD or vascular dementia and adverse outcomes in AF patients. METHODS: Cohort study between January 2000 and 2017. AF patients were divided into two groups according to vascular dementia or AD, and balanced using propensity score matching (PSM). During 4-years of follow-up, incident intracranial hemorrhages (ICH), the composite of ischemic stroke/transient ischemic attack (TIA), hospitalizations, and all-cause deaths, were recorded. RESULTS: Two thousand three hundred seventy-seven AF patients with dementia (1225 with vascular dementia, and 1152 with AD) were identified. Following a PSM, 615 patients were included in each cohort (i.e., 1:1) and all variables were well-matched. After PSM, 22 (3.6%) patients with vascular dementia and 55 (8.1%) patients with AD had incident ICH during follow-up (hazard ratio [HR]: 2.22, 95% confidence interval [CI]: 1.33-3.70, log-rank p = 0.002). Overall, 237 (38.5%) patients with vascular dementia and 193 (31.4%) patients with AD, developed an ischemic stroke/TIA. The risk of ischemic stroke/TIA was 1.32-fold higher in vascular dementia (HR: 1.32, 95% CI: 1.09-1.59, log-rank p = 0.003). The risk of rehospitalization (HR: 1.14, 95% CI: 1.01-1.31), and mortality (HR: 1.25, 95% CI: 1.01-1.58) were also higher among AF patients with vascular dementia compared to AD. CONCLUSIONS: The two forms of dementia in AF patients are associated with different prognosis, with AD being associated with a higher risk of ICH, and vascular dementia with a higher risk of stroke/TIA, hospitalization, and mortality.

C-reactive protein levels are associated with early cardiac complications or death in patients with acute ischemic stroke: a propensity-matched analysis of a global federated health from the TriNetX network.

The role of inflammation in predicting early cardiac complications among stroke patients is unclear. Electronic medical records from TriNetX, a global federated health research network, were used for this retrospective analysis. Patients with ischemic stroke and C-Reactive Protein (CRP) levels measured within 24 h post-stroke were categorized into three groups: (i) < 1 mg/L, (ii)1-3 mg/L and (iii) > 3 mg/L. The primary outcome was a composite outcome of cardiac complications (heart failure (HF), ischemic heart disease, atrial fibrillation (AF), ventricular arrhythmias and Takotsubo cardiomyopathy) or death at 30 days from the index event. Cox-regression analyses were used to produce hazard ratios (HRs) and 95% confidence intervals (CI) following 1:1 propensity score matching (PSM). Of the 104,741 patients enrolled, 51% were female and the mean age was 66 ± 16 years. After PSM, a new cardiac complication or death within 30 days occurred in 5624 (33.1%) patients with CRP > 3 mg/L, in 4243 (25.6%) patients with CRP 1-3 mg/L and in 3891 (23.5%) patients with CRP < 1 mg/L. Patients with CRP levels of 1-3 mg/L and > 3 mg/L had higher risk of the composite outcome (HR 1.10, 95%CI 1.05-1.52; HR 1.51, 95%CI 1.45-1.58), death (HR 1.43, 95%CI 1.24-1.64; HR 3.50, 95%CI 3.01-3.96), HF (HR 1.08, 95%CI 1.01-1.16; HR 1.51, 95%CI 1.41-1.61), AF (HR 1.10, 95% CI:1.02-1.18; HR 1.42, 95%CI 1.33-1.52) and ventricular arrhythmias (HR 1.25, 95%CI 1.02-1.52; HR 1.67, 95% CI 1.38-2.01) compared to those with CRP < 1 mg/L. Ischemic heart disease were more common among patients with CRP levels > 3 mg/L compared to those with CRP < 1 mg/L (HR:1.33, 95% CI:1.26-1.40), while no association with Takotsubo cardiomyopathy was found in all the analyses. CRP levels within the first 24 h of an ischemic stroke predict 30-day cardiac complications or death.

Pregnancy-Related Complications and Incidence of Atrial Fibrillation: A Systematic Review.

Pregnancy-related complications are associated with a higher risk of various incident cardiovascular diseases, but their specific potential relationship with incident atrial fibrillation (AF) is less clear. This systematic review summarises the available evidence from observational studies which have examined associations between pregnancy-related complications and the risk of AF. MEDLINE and EMBASE (Ovid) were searched for studies between 1990 to 10 February 2022. Pregnancy-related complications examined included hypertensive disorders of pregnancy (HDP), gestational diabetes, placental abruption, preterm birth, small-for-gestational-age and stillbirth. Study selection, data extraction and quality assessment were completed independently by two reviewers. Narrative synthesis was used to evaluate the results of the included studies. Nine observational studies were included, with eight eligible for narrative synthesis. Sample sizes ranged from 1839 to 2,359,386. Median follow-up ranged from 2 to 36 years. Six studies reported that pregnancy-related complications were associated with a significantly increased risk of incident AF. Hazard ratios (HRs) (95% confidence intervals) for the four studies that evaluated HDP ranged from 1.1 (0.8-1.6) to 1.9 (1.4-2.7). For the four studies that evaluated pre-eclampsia, HRs ranged from 1.2 (0.9-1.6) to 1.9 (1.7-2.2). Current evidence from observational studies suggests pregnancy-related complications are associated with a significantly higher risk of incident AF. However, only a small number of studies examining each pregnancy-related complication were identified, and considerable statistical heterogeneity was observed. Further large-scale prospective studies are required to confirm the association between pregnancy-related complications and incident AF.

Antiplatelet Agents and Oral Anticoagulant Use in Patients with Atrial Fibrillation and Carotid Artery Disease After First-Time Ischaemic Stroke.

INTRODUCTION: People with atrial fibrillation (AF) frequently have competing mechanisms for ischaemic stroke, including extracranial carotid atherosclerosis. The objective of this study was to determine associations between use of oral anticoagulants (OACs) plus antiplatelet agents (APA) after ischaemic stroke and outcomes for patients with AF and carotid artery disease. PATIENTS AND METHODS: A retrospective cohort study was conducted. Participants receiving OACs with or without APA were propensity score-matched for age, sex, ethnicity, co-morbidities and presence of cardiac and vascular implants and grafts. Outcomes were 1-year mortality, recurrent stroke and major bleeding. RESULTS: Of 5708 patients, 24.1% (n=1628) received non-vitamin K antagonist OACs (NOACs) with no APA, 26.0% (n=1401) received NOACs plus APA, 20.7% (n=1243) received warfarin without APA and 29.2% (n=1436) received warfarin plus APA. There was no significant difference in risk of recurrent stroke between the groups. Compared to receiving NOACs without APA, receiving warfarin plus APA was associated with a higher risk of mortality (hazard ratio (HR) 1.51 (95% confidence interval (CI) 1.20, 1.89)) and major bleeding (HR 1.66 (95% CI 1.40, 1.96)). Receiving NOACs plus APA was also associated with a higher risk of major bleeding compared to NOACs without APA (HR 1.27 (95% CI 1.07, 1.51), respectively). CONCLUSIONS: The results suggest for patients with AF and carotid artery disease after ischaemic stroke, receiving NOACs without APA is associated with a lower risk of major bleeding with no negative impact on recurrent stroke or mortality. Evidence from randomised trials is needed to confirm this finding.

Regional Cerebral Blood Flow Changes in Healthy Ageing and Alzheimer's Disease: A Narrative Review.

BACKGROUND: Cerebral blood flow is known to decline with increasing age and is a potential biomarker to distinguish between healthy and unhealthy ageing, where healthy ageing is defined as an absence of comorbidities in senescence. This review aims to synthesize evidence of cerebral blood flow changes over multiple brain regions, for use as a clinical reference or for in silico modelling. SUMMARY: The search identified 1,087 studies, of which 33 met the inclusion criteria to map the difference in cerebral blood flow reduction between healthy ageing and Alzheimer's disease. Analysis was also performed on the effect of imaging modality and brain region functionality as potential confounding factors. KEY MESSAGES: No significant difference was found between the specific functionality of a brain region and cerebral blood flow in healthy ageing (p = 0.65) or Alzheimer's disease (p = 0.42). Arterial spin labelling MRI imaging was shown to measure statistically larger decreases in flow in both healthy ageing (p = 0.0001) and Alzheimer's disease (p = 0.0465). Cerebral blood flow was shown to decrease 0.3-0.5% per year in healthy ageing, which increased to a decline of 2-5% per year in Alzheimer's disease. There was large variability both between and within individual brain regions, and this variability increased greatly in Alzheimer's disease. Future studies would add value by taking more cerebral blood flow measurements during Alzheimer's disease progression and by investigating ageing with comorbidities such as hypertension.

Outcomes in patients with ischaemic stroke undergoing endovascular thrombectomy: Impact of atrial fibrillation.

OBJECTIVES: Endovascular thrombectomy (EVT) is associated with good clinical outcomes in ischaemic stroke, but the risk of intracerebral haemorrhage (ICH) and mortality remains common following ischaemic stroke. The effect of concomitant atrial fibrillation (AF) on clinical outcomes following acute ischaemic stroke in patients receiving EVT remains unclear. The aim is to investigate associations between AF and intracerebral haemorrhage and all-cause mortality at 90 days in patients with ischaemic stroke undergoing EVT. MATERIALS AND METHODS: A retrospective cohort was conducted using TriNetX, a global health research network. The network was searched for people aged ≥18 years with ischaemic stroke, EVT and AF recorded in electronic medical records between 01/09/2018 and 01/09/2021. These patients were compared to controls with ischaemic stroke, EVT and no AF. Propensity score matching for age, sex, race, comorbidities, National Institutes of Health Stroke Scale (NIHSS) scores, and prior use of anticoagulation was used to balance the cohorts with and without AF. RESULTS: In total 3,106 patients were identified with history of ischaemic stroke treated by EVT. After propensity-score matching, 832 patients (mean age 68 ± 13; 47% female) with ischaemic stroke, EVT and AF, were compared to 832 patients (mean age 67 ± 12; 47% female) with ischaemic stroke, EVT and no history of AF. In the cohort with AF, 11.5% (n = 96) experienced ICH within 90 days following EVT, compared with 12.3% (n = 103) in patients without AF (Odds Ratio (OR) 0.92, 95% confidence interval (CI) 0.68-1.24; p = 0.59). In the patients with AF, mortality within 90 days following EVT was 18.7% (n = 156), compared with 22.5% in patients without AF (n = 187) (OR 0.79, 95% CI 0.63-1.01; p = 0.06). CONCLUSION: In patients with ischaemic stroke undergoing EVT, AF was not significantly associated with intracerebral haemorrhage or all-cause mortality at 90-day follow-up.

Endovascular treatment for ischemic stroke patients with and without atrial fibrillation, and the effects of adjunctive pharmacotherapy: a narrative review.

INTRODUCTION: Endovascular thrombectomy (EVT) is associated with good clinical outcomes in patients with ischemic stroke, but the impact of EVT on clinical outcomes in patients with ischemic stroke with and without atrial fibrillation (AF), and the effect of adjunctive pharmacological therapies with EVT, remains unclear. AREAS COVERED: The goal of this narrative review is to provide an overview of studies which have examined: 1) associations between EVT and outcomes for patients following ischemic stroke, 2) associations between EVT and outcomes for patients following ischemic stroke with and without AF , including function, reperfusion, hemorrhage, and mortality, 3) the effect of adjunctive pharmacological therapies peri- and post-thrombectomy, and 4) integration of prehospital care on endovascular treatment outcomes. EXPERT OPINION: There is little evidence from randomized controlled trials on the effect of AF on stroke outcomes following EVT and the safety and efficacy of AF treatment in the peri-EVT such as tirofiban or Intravenous thrombolysis with Non-vitamin K Antagonist Oral Anticoagulant. The available evidence from observational studies on AF and EVT outcomes is inconsistent, but factors such as procedural EVT devices, the center volume, clinician experience, stroke recognition, and inclusion criteria of studies have all been associated with poorer clinical outcomes. Enhancing the clinical network among prehospital and hospitals will facilitate direct transfer to EVT centers, reducing stroke onset to EVT time and optimizing stroke outcomes.