Pre-morbid sleep disturbance and its association with stroke severity: results from the international INTERSTROKE study.

BACKGROUND AND PURPOSE: Whilst sleep disturbances are associated with stroke, their association with stroke severity is less certain. In the INTERSTROKE study, the association of pre-morbid sleep disturbance with stroke severity and functional outcome following stroke was evaluated. METHODS: INTERSTROKE is an international case-control study of first acute stroke. This analysis included cases who completed a standardized questionnaire concerning nine symptoms of sleep disturbance (sleep onset latency, duration, quality, nocturnal awakening, napping duration, whether a nap was planned, snoring, snorting and breathing cessation) in the month prior to stroke (n = 2361). Two indices were derived representing sleep disturbance (range 0-9) and obstructive sleep apnoea (range 0-3) symptoms. Logistic regression was used to estimate the magnitude of association between symptoms and stroke severity defined by the modified Rankin Score. RESULTS: The mean age of participants was 62.9 years, and 42% were female. On multivariable analysis, there was a graded association between increasing number of sleep disturbance symptoms and initially severe stroke (2-3, odds ratio [OR] 1.44, 95% confidence interval [CI] 1.07-1.94; 4-5, OR 1.66, 95% CI 1.23-2.25; >5, OR 2.58, 95% CI 1.83-3.66). Having >5 sleep disturbance symptoms was associated with significantly increased odds of functional deterioration at 1 month (OR 1.54, 95% CI 1.01-2.34). A higher obstructive sleep apnoea score was also associated with significantly increased odds of initially severe stroke (2-3, OR 1.48; 95% CI 1.20-1.83) but not functional deterioration at 1 month (OR 1.19, 95% CI 0.93-1.52). CONCLUSIONS: Sleep disturbance symptoms were common and associated with an increased odds of severe stroke and functional deterioration. Interventions to modify sleep disturbance may help prevent disabling stroke/improve functional outcomes and should be the subject of future research.

Blood pressure variability in acute stroke: Risk factors and association with functional outcomes at 1 month.

BACKGROUND AND PURPOSE: Blood pressure variability, in acute stroke, may be an important modifiable determinant of functional outcome after stroke. In a large international cohort of participants with acute stroke, it was sought to determine the association of blood pressure variability (in the early period of admission) and functional outcomes, and to explore risk factors for increased blood pressure variability. PATIENTS AND METHODS: INTERSTROKE is an international case-control study of risk factors for first acute stroke. Blood pressure was recorded at the time of admission, the morning after admission and the time of interview in cases (median time from admission 36.7 h). Multivariable ordinal regression analysis was employed to determine the association of blood pressure variability (standard deviation [SD] and coefficient of variance) with modified Rankin score at 1-month follow-up, and logistic regression was used to identify risk factors for blood pressure variability. RESULTS: Amongst 13,206 participants, the mean age was 62.19 ± 13.58 years. When measured by SD, both systolic blood pressure variability (odds ratio 1.13; 95% confidence interval 1.03-1.24 for SD ≥20 mmHg) and diastolic blood pressure variability (odds ratio 1.15; 95% confidence interval 1.04-1.26 for SD ≥10 mmHg) were associated with a significant increase in the odds of poor functional outcome. The highest coefficient of variance category was not associated with a significant increase in risk of higher modified Rankin score at 1 month. Increasing age, female sex, high body mass index, history of hypertension, alcohol use, and high urinary potassium and low urinary sodium excretion were associated with increased blood pressure variability. CONCLUSION: Increased blood pressure variability in acute stroke, measured by SD, is associated with an increased risk of poor functional outcome at 1 month. Potentially modifiable risk factors for increased blood pressure variability include low urinary sodium excretion.

Bias assessment and correction for Levin's population attributable fraction in the presence of confounding.

In 1953, Morton Levin introduced a simple approach to estimating population attributable fractions (PAF) depending only on risk factor prevalence and relative risk. This formula and its extensions are still in widespread use today, particularly to estimate PAF in populations where individual data is unavailable. Unfortunately, Levin's approach is known to be asymptotically biased for the PAF when the risk factor-disease relationship is confounded even if relative risks that are correctly adjusted for confounding are used in the estimator. Here we describe a simple re-expression of Miettinen's estimand that depends on the causal relative risk, the unadjusted relative risk and the population risk factor prevalence. While this re-expression is not new, it has been underappreciated in the literature, and the associated estimator may be useful in estimating PAF in populations when individual data is unavailable provided estimated adjusted and unadjusted relative risks can be transported to the population of interest. Using the re-expressed estimand, we develop novel analytic formulae for the relative and absolute asymptotic bias in Levin's formula, solidifying earlier work by Darrow and Steenland that used simulations to investigate this bias. We extend all results to settings with non-binary valued risk factors and continuous exposures and discuss the utility of these results in estimating PAF in practice.

Markers of periodontal disease and risk of stroke: INTERSTROKE case-control study.

BACKGROUND: Periodontal disease may be an important modifiable risk factor for stroke. AIMS: To determine the contribution of markers of periodontal disease to stroke risk globally, within subpopulations, and by stroke subtypes. METHODS: INTERSTROKE is the largest international case-control study of risk factors for first acute stroke. All participants were asked a standardised set of questions about the presence or absence of painful teeth, painful gums or lost teeth, as markers of periodontal disease, within the previous year. The total number of reported variables was calculated per participant. Multivariable conditional logistic regression examined the association of these variables with acute stroke. RESULTS: In 26901 participants, across 32 countries, there was a significant multivariable association between lost teeth and stroke (OR 1.11, 95 % CI 1.01 - 1.22), but not painful teeth (OR 1.00, 95 % CI 0.91-1.10) or painful gums (OR 1.01, 95 % CI 0.89 - 1.14). When these symptoms were considered together there was a graded increased odds of stroke, with the largest magnitude of association seen if a patient reported all three of painful teeth, painful gums and lost teeth (OR 1.34, 95 % CI 1.00 - 1.79). CONCLUSIONS: Our findings suggest that features of severe periodontal disease are a risk factor for acute stroke. Periodontal disease should be considered as a potentially modifiable risk factor for stroke.

Global mean potassium intake: a systematic review and Bayesian meta-analysis.

PURPOSE: Increasing potassium intake, especially in populations with low potassium intake and high sodium intake, has emerged as an important population-level intervention to reduce cardiovascular events. Current guideline recommendations, such as those made by the World Health Organisation, recommend a potassium intake of  > 3.5 g/day. We sought to determine summary estimates for mean potassium intake and sodium/potassium (Na/K) ratio in different regions of the world. METHODS: We performed a systematic review and meta-analysis. We identified 104 studies, that included 98 nationally representative surveys and 6 multi-national studies. To account for missingness and incomparability of data, a Bayesian hierarchical imputation model was applied to estimating summary estimates of mean dietary potassium intake (primary outcome) and sodium/potassium ratio. RESULTS: Overall, 104 studies from 52 countries were included (n = 1,640,664). Mean global potassium intake was 2.25 g/day (57 mmol/day) (95% credible interval (CI) 2.05-2.44 g/day), with highest intakes in Eastern and Western Europe (mean intake 3.53g/day, 95% CI 3.05-4.01 g/day and 3.29 g/day, 95% CI 3.13-3.47 g/day, respectively) and lowest intakes in East Asia (mean intake 1.89 g/day; 95% CI 1.55-2.25 g/day). Approximately 31% (95% CI, 30-41%) of global population included have an estimated potassium intake  > 2.5 g/day, with 14% (95% CI 11-17%) above 3.5 g/day. CONCLUSION: Global mean potassium intake (2.25 g/day) falls below current guideline recommended intake level of  > 3.5 g/day, with only 14% (95% CI 11-17%) of the global population achieving guideline-target mean intake. There was considerable regional variation, with lowest mean potassium intake reported in Asia, and highest intake in Eastern and Western Europe.

Comparing functional and quality of life outcomes in transcatheter aortic valve implantation and surgical aortic valve replacement for aortic stenosis: a systematic review and meta-analysis.

BACKGROUND: To compare functional and health related quality of life outcomes post-transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) in patients with critical aortic stenosis (AS) across low to high-risk surgical candidates. These patient-centred factors will be compared between both groups in the short to medium term time frames and will aid in shared decision making between patients and healthcare workers. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis of randomised controlled trials which compared TAVI with SAVR and reported on quality of life (QoL) and functional scores. The scores used were the Kansas City Cardiomyopathy Questionnaire (KCCQ), Euroqol-5DL (EQ5DL), the short form-36/12 (SF-36/12) and the NYHA. RESULTS: We identified eight trials with a total of 8898 participants. Both groups showed improvements from baseline at one month. At one month there was a statistically significant difference in standardised mean difference (SMD) in favour of TAVI for EQ5DL (SMD 0.37, 95% CI 0.26,0.49), KCCQ (SMD 0.53,95% CI 0.48, 0.58), SF physical summary (SMD 0.55, 95% CI 0.31 - 0.78) and SF mental summary (SMD 0.34, 95% CI 0.27 - 0.40). At one year there was no statistically significant difference between any of these QoL metrics. For NYHA, no significant difference in odds ratio of class III/IV was observed at one month between TAVI and SAVR (OR 0.94, 95% CI 0.83, 1.07), however, TAVI was associated with reduced odds ratio of NYHA class I/II at one year (OR 0.87, 95% CI 0.78, 0.98). CONCLUSION: Both groups were associated with improvements in QoL and functional outcomes with TAVI reporting more significant improvements in QoL at one-month post-procedures. No significant improvements between groups were seen at one year. This is the largest meta-analysis comparing post-operative health-related quality of life outcomes post SAVR and TAVI and has major implications in shared decision making for the treatment of aortic stenosis.

Antiplatelet therapy and incident cognitive impairment or dementia-a systematic review and meta-analysis of randomised clinical trials.

OBJECTIVE: The benefit of antiplatelet therapy in preventing cognitive impairment or dementia is uncertain. We investigated the association between antiplatelet therapy and incident cognitive impairment or dementia in randomised clinical trials. METHODS: We searched PubMed, EMBASE and CENTRAL for randomised clinical trials published from database inception through 1 February 2023. Trials that evaluated the association of antiplatelet therapy with incident cognitive impairment or dementia were included. For single-agent antiplatelet, the control group was placebo. For dual agent antiplatelet therapy, the control group was single-agent monotherapy. A random-effects meta-analysis model was used to report pooled treatment effects and 95% confidence intervals (CIs). The primary outcome was incident cognitive impairment or dementia. Secondary outcomes included change in cognitive test scores. RESULTS: A total of 11 randomised clinical trials were included (109,860 participants). All reported the incidence of cognitive impairment or dementia on follow-up. The mean (SD) age of trial participants was 66.2 (7.9) years. Antiplatelet therapy was not significantly associated with a reduced risk of cognitive impairment or dementia (11 trials; 109,860 participants) (3.49% versus 4.18% of patients over a mean trial follow-up of 5.8 years; odds ratio [OR], 0.94 [95% CI, 0.88-1.00]; absolute risk reduction, 0.2% [95% CI, -0.4% to 0.009%]; I2 = 0.0%). Antiplatelet therapy was not significantly associated with mean change in cognitive test scores. CONCLUSION: In this meta-analysis, antiplatelet therapy was not significantly associated with a lower risk of incident cognitive impairment or dementia, but the CIs around this outcome do not exclude a modest preventative effect.

Randomised controlled trials of antihypertensive therapy: does exclusion of orthostatic hypotension alter treatment effect? A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Management of antihypertensive therapy is challenging in patients with symptomatic orthostatic hypotension, a population often excluded from randomised controlled trials of antihypertensive therapy. In this systematic review and meta-analysis, we sought to determine whether the association of antihypertensive therapy and adverse events (e.g. falls, syncope), differed among trials that included or excluded patients with orthostatic hypotension. METHODS: We performed a systematic review and meta-analysis of randomised controlled trials comparing blood pressure lowering medications to placebo, or different blood pressure targets on falls or syncope outcomes and cardiovascular events. A random-effects meta-analysis was used to estimate a pooled treatment-effect overall in subgroups of trials that excluded patients with orthostatic hypotension and trials that did not exclude patients with orthostatic hypotension, and tested P for interaction. The primary outcome was fall events. RESULTS: 46 trials were included, of which 18 trials excluded orthostatic hypotension and 28 trials did not. The incidence of hypotension was significantly lower in trials that excluded participants with orthostatic hypotension (1.3% versus 6.2%, P < 0.001) but not incidences of falls (4.8% versus 8.8%; P = 0.40) or syncope (1.5% versus 1.8%; P = 0.67). Antihypertensive therapy was not associated with an increased risk of falls in trials that excluded (OR 1.00, 95% CI; 0.89-1.13) or included (OR 1.02, 95% CI; 0.88-1.18) participants with orthostatic hypotension (P for interaction = 0.90). CONCLUSIONS: The exclusion of patients with orthostatic hypotension does not appear to affect the relative risk estimates for falls and syncope in antihypertensive trials.

Development and assessment of the performance of a shared ventilatory system that uses clinically available components to individualize tidal volumes.

OBJECTIVES: To develop and assess a system for shared ventilation using clinically available components to individualize tidal volumes. DESIGN: Evaluation and in vitro validation study SETTING: Ventilator shortage during the SARS-CoV-2 pandemic. PARTICIPANTS: The team consisted of physicians, bioengineers, computer programmers, and medical technology professionals. METHODS: Using clinically available components, a system of ventilation consisting of two ventilatory limbs was assembled and connected to a ventilator. Monitors for each limb were developed using open-source software. Firstly, the effect of altering ventilator settings on tidal volumes delivered to each limb was determined. Secondly, the impact of altering the compliance and resistance of one limb on the tidal volumes delivered to both limbs was analysed. Experiments were repeated three times to determine system variability. RESULTS: The system permitted accurate and reproducible titration of tidal volumes to each limb over a range of ventilator settings and simulated lung conditions. Alteration of ventilator inspiratory pressures, of respiratory rates, and I:E ratio resulted in very similar tidal volumes delivered to each limb. Alteration of compliance and resistance in one limb resulted in reproducible alterations in tidal volume to that test lung, with little change to tidal volumes in the other lung. All tidal volumes delivered were reproducible. CONCLUSIONS: We demonstrate the reliability of a shared ventilation system assembled using commonly available clinical components that allows titration of individual tidal volumes. This system may be useful as a strategy of last resort for Covid-19, or other mass casualty situations, where the need for ventilators exceeds supply.

Role of Proxy Respondents in International Stroke Research: Experience of the INTERSTROKE Study.

INTRODUCTION: Measuring patient-reported information in stroke research is challenging. To overcome this, use of proxy respondents is often a necessary strategy. In this study, we report on use and effect of proxy respondents on patient case-mix in a large international epidemiologic stroke study (INTERSTROKE). METHODS: This was a cross-sectional study of 13,458 cases of acute first stroke in 32 countries. A standardized study questionnaire recording behavioural cardiovascular risk factors was administered to the patient, and if unable to communicate adequately, a valid proxy, or both. We used logistic regression to evaluate the association of age, sex, education, occupation, stroke severity, and region with need for proxy respondent, and report odds ratio (OR) with 95% confidence interval (CI). RESULTS: Among 13,458 participants with acute stroke, questionnaires were completed by patients alone in 41.4% (n = 5,573), combination of patient and proxy together in 21.7% (n = 2,918), and proxy alone in 36.9% (n = 4,967). Use of proxy alone was greater in participants with severe stroke (4.7% with modified-Rankin score of 0 vs. 80.5% in those with score 5; OR 187.13; 95% CI: 119.61-308.22), older persons (43.8% of those aged 80 years and over vs. 33.2% of those aged less than 40 years; age per decade OR 1.09; 95% CI: 1.06-1.12), women (40.7% vs. 34.3% of men; OR 1.32 95% CI: 1.22-1.43), and those less educated (58.9% of those never educated vs. 25.7% of those who attended third level education; OR 7.84; 95% CI: 6.78-9.08). CONCLUSION: Use of proxy respondents enhances the generalizability of international research studies of stroke, by increasing representation of women, patients with severe stroke, older age, and lower education.

Radiology artificial intelligence: a systematic review and evaluation of methods (RAISE).

OBJECTIVE: There has been a large amount of research in the field of artificial intelligence (AI) as applied to clinical radiology. However, these studies vary in design and quality and systematic reviews of the entire field are lacking.This systematic review aimed to identify all papers that used deep learning in radiology to survey the literature and to evaluate their methods. We aimed to identify the key questions being addressed in the literature and to identify the most effective methods employed. METHODS: We followed the PRISMA guidelines and performed a systematic review of studies of AI in radiology published from 2015 to 2019. Our published protocol was prospectively registered. RESULTS: Our search yielded 11,083 results. Seven hundred sixty-seven full texts were reviewed, and 535 articles were included. Ninety-eight percent were retrospective cohort studies. The median number of patients included was 460. Most studies involved MRI (37%). Neuroradiology was the most common subspecialty. Eighty-eight percent used supervised learning. The majority of studies undertook a segmentation task (39%). Performance comparison was with a state-of-the-art model in 37%. The most used established architecture was UNet (14%). The median performance for the most utilised evaluation metrics was Dice of 0.89 (range .49-.99), AUC of 0.903 (range 1.00-0.61) and Accuracy of 89.4 (range 70.2-100). Of the 77 studies that externally validated their results and allowed for direct comparison, performance on average decreased by 6% at external validation (range increase of 4% to decrease 44%). CONCLUSION: This systematic review has surveyed the major advances in AI as applied to clinical radiology. KEY POINTS: • While there are many papers reporting expert-level results by using deep learning in radiology, most apply only a narrow range of techniques to a narrow selection of use cases. • The literature is dominated by retrospective cohort studies with limited external validation with high potential for bias. • The recent advent of AI extensions to systematic reporting guidelines and prospective trial registration along with a focus on external validation and explanations show potential for translation of the hype surrounding AI from code to clinic.

The Clinical Application of Urine Soluble CD163 in ANCA-Associated Vasculitis.

BACKGROUND: Up to 70% of patients with ANCA-associated vasculitis (AAV) develop GN, with 26% progressing to ESKD. Diagnostic-grade and noninvasive tools to detect active renal inflammation are needed. Urinary soluble CD163 (usCD163) is a promising biomarker of active renal vasculitis, but a diagnostic-grade assay, assessment of its utility in prospective diagnosis of renal vasculitis flares, and evaluation of its utility in proteinuric states are needed. METHODS: We assessed a diagnostic-grade usCD163 assay in (1) a real-world cohort of 405 patients with AAV and 121 healthy and 488 non-AAV disease controls; (2) a prospective multicenter study of 84 patients with potential renal vasculitis flare; (3) a longitudinal multicenter cohort of 65 patients with podocytopathy; and (4) a cohort of 29 patients with AAV (with or without proteinuria) and ten controls. RESULTS: We established a diagnostic reference range, with a cutoff of 250 ng/mmol for active renal vasculitis (area under the curve [AUC], 0.978). Using this cutoff, usCD163 was elevated in renal vasculitis flare (AUC, 0.95) but remained low in flare mimics, such as nonvasculitic AKI. usCD163's specificity declined in patients with AAV who had nephrotic-range proteinuria and in those with primary podocytopathy, with 62% of patients with nephrotic syndrome displaying a "positive" usCD163. In patients with AAV and significant proteinuria, usCD163 normalization to total urine protein rather than creatinine provided the greatest clinical utility for diagnosing active renal vasculitis. CONCLUSIONS: usCD163 is elevated in renal vasculitis flare and remains low in flare mimics. Nonspecific protein leakage in nephrotic syndrome elevates usCD163 in the absence of glomerular macrophage infiltration, resulting in false-positive results; this can be corrected with urine protein normalization.

Association of Oral Anticoagulation With Stroke in Atrial Fibrillation or Heart Failure: A Comparative Meta-Analysis.

Background and Purpose: Atrial fibrillation and heart failure with reduced ejection fraction (HFrEF) are common sources of cardioembolism. While oral anticoagulation is strongly recommended for atrial fibrillation, there are marked variations in guideline recommendations for HFrEF due to uncertainty about net clinical benefit. This systematic review and meta-analysis evaluates the comparative association of oral anticoagulation with stroke and other cardiovascular risk in populations with atrial fibrillation or HFrEF in sinus rhythm and identify factors mediating different estimates of net clinical benefit. Methods: PubMed and Embase were searched from database inception to November 20, 2019 for randomized clinical trials comparing oral anticoagulation to control. A random-effects meta-analysis was used to estimate a pooled treatment-effect overall and within atrial fibrillation and HFrEF trials. Differences in treatment effect were assessed by estimating I2 among all trials and testing the between-trial-population P-interaction. The primary outcome measure was all stroke. Secondary outcome measures were ischemic stroke, hemorrhagic stroke, mortality, myocardial infarction, and major hemorrhage. Results: Twenty-one trials were eligible for inclusion, 15 (n=19 332) in atrial fibrillation (mean follow-up: 23.1 months), and 6 (n=9866) in HFrEF (mean follow-up: 23.9 months). There were differences in primary outcomes between trial populations, with all-cause mortality included for 95.2% of HFrEF trial population versus 0.38% for atrial fibrillation. Mortality was higher in controls groups of HFrEF populations (19.0% versus 9.6%) but rates of stroke lower (3.1% versus 7.0%) compared with atrial fibrillation. The association of oral anticoagulation with all stroke was consistent for atrial fibrillation (odds ratio, 0.51 [95% CI, 0.42­0.63]) and HFrEF (odds ratio, 0.61 [95% CI, 0.47­0.79]; I2=12.4%; P interaction=0.31). There were no statistically significant differences in the association of oral anticoagulation with cardiovascular events, mortality or bleeding between populations. Conclusions: The relative association of oral anticoagulation with stroke risk, and other cardiovascular outcomes, is similar for patients with atrial fibrillation and HFrEF. Differences in the primary outcomes employed by trials in HFrEF, compared with atrial fibrillation, may have contributed to differing conclusions of the relative efficacy of oral anticoagulation.

Renal Impairment and Risk of Acute Stroke: The INTERSTROKE Study.

BACKGROUND: Previous studies reported an association of renal impairment with stroke, but there are uncertainties underpinning this association. AIMS: We explored if the association is explained by shared risk factors or is independent and whether there are regional or stroke subtype variations. METHODS: INTERSTROKE is a case-control study and the largest international study of risk factors for first acute stroke, completed in 27 countries. We included individuals with available serum creatinine values and calculated estimated glomerular filtration rate (eGFR). Renal impairment was defined as eGFR <60 mL/min/1.73 m2. Multivariable conditional logistic regression was used to determine the association of renal function with stroke. RESULTS: Of 21,127 participants, 41.0% were female, the mean age was 62.3 ± 13.4 years, and the mean eGFR was 79.9 ± 23.5 mL/min/1.73 m2. The prevalence of renal impairment was higher in cases (22.9% vs. 17.7%, p < 0.001) and differed by region (p < 0.001). After adjustment, lower eGFR was associated with increased odds of stroke. Renal impairment was associated with increased odds of all stroke (OR 1.35; 95% CI: 1.24-1.47), with higher odds for intracerebral hemorrhage (OR 1.60; 95% CI: 1.35-1.89) than ischemic stroke (OR 1.29; 95% CI: 1.17-1.42) (pinteraction 0.12). The largest magnitudes of association were seen in younger participants and those living in Africa, South Asia, or South America (pinteraction < 0.001 for all stroke). Renal impairment was also associated with poorer clinical outcome (RRR 2.97; 95% CI: 2.50-3.54 for death within 1 month). CONCLUSION: Renal impairment is an important risk factor for stroke, particularly in younger patients, and is associated with more severe stroke and worse outcomes.

Exploring population pharmacokinetic models in patients treated with vancomycin during continuous venovenous haemodiafiltration (CVVHDF).

BACKGROUND: Therapeutic antibiotic dose monitoring can be particularly challenging in septic patients requiring renal replacement therapy. Our aim was to conduct an exploratory population pharmacokinetic (PK) analysis on PK of vancomycin following intermittent infusion in critically ill patients receiving continuous venovenous haemodiafiltration (CVVHDF); focussing on the influence of dialysis-related covariates. METHODS: This was a retrospective single-centre tertiary level intensive care unit (ICU) study, which included patients treated concurrently with vancomycin and CVVHDF between January 2015 and July 2016. We extracted clinical, laboratory and dialysis data from the electronic healthcare record (EHR), using strict inclusion criteria. A population PK analysis was conducted with a one-compartment model using the PMetrics population PK modelling package. A base structural model was developed, with further analyses including clinical and dialysis-related data to improve model prediction through covariate inclusion. The final selected model simulated patient concentrations using probability of target attainment (PTA) plots to investigate the probability of different dosing regimens achieving target therapeutic concentrations. RESULTS: A total of 106 vancomycin dosing intervals (155 levels) in 24 patients were examined. An acceptable 1-compartment base model was produced (Plots of observed vs. population predicted concentrations (Obs-Pred) R2 = 0.78). No continuous covariates explored resulted in a clear improvement over the base model. Inclusion of anticoagulation modality and vasopressor use as categorical covariates resulted in similar PK parameter estimates, with a trend towards lower parameter estimate variability when using regional citrate anti-coagulation or without vasopressor use. Simulations using PTA plots suggested that a 2 g loading dose followed by 750 mg 12 hourly as maintenance dose, commencing 12 h after loading, is required to achieve adequate early target trough concentrations of at least 15 mg/L. CONCLUSIONS: PTA simulations suggest that acceptable trough vancomycin concentrations can be achieved early in treatment with a 2 g loading dose and maintenance dose of 750 mg 12 hourly for critically ill patients on CVVHDF.

Stroke Severity in Transcatheter Aortic Valve Implantation Versus Surgical Aortic Valve Replacement: A Systematic Review and Meta-Analysis.

OBJECTIVES: An assessment of the comparative incidence of fatal or disabling stroke may influence choice of intervention for patients with severe aortic stenosis. We explored whether transcatheter aortic valve implantation (TAVI) is associated with a lower incidence of fatal or disabling stroke, compared to surgical aortic valve replacement (SAVR). MATERIALS & METHODS: We classified stroke into two categories; fatal or disabling, or non-disabling, and completed meta-analyses for each. We explored randomised controlled trials to assess the effect publication year, predicted operative risk, and route of TAVI access. RESULTS: There was no difference between treatment groups per 100 person years of follow up for disabling or non-disabling stroke outcomes. In a stratified analysis by year of publication, there was a lower rate of fatal or disabling stroke with TAVI in trials published after 2015, compared to those published in 2015 or before (p-interaction = 0.01 at 30 days). Higher proportions of transfemoral route access (>90%), more common in recent trials, were associated with a lower rate of fatal or disabling stroke (p-interaction = 0.03 at 30 days). Lower average surgical risk scores were associated with lower rates of fatal or disabling stroke (p = 0.02 at 30 days). CONCLUSION: We found that treatment of aortic stenosis with TAVI compared with SAVR was not associated with an overall reduced risk in fatal or disabling stroke. Subgroup analyses suggested a lower risk of fatal or disabling stroke with TAVI in situations which reflect contemporary practice.

Virtual geriatric clinics and the COVID-19 catalyst: a rapid review.

BACKGROUND: During the current COVID-19 health crisis virtual geriatric clinics have become increasingly utilised to complete outpatient consultations, although concerns exist about feasibility of such virtual consultations for older people. The aim of this rapid review is to describe the satisfaction, clinic productivity, clinical benefit, and costs associated with the virtual geriatric clinic model of care. METHODS: A rapid review of PubMed, MEDLINE and CINAHL databases was conducted up to April 2020. Two independent reviewers extracted the information. Four subdomains were focused on: satisfaction with the virtual geriatric clinic, clinic productivity, clinical benefit to patients, costs and any challenges associated with the virtual clinic process. RESULTS: Nine studies with 975 patients met our inclusion criteria. All were observational studies. Seven studies reported patients were satisfied with the virtual geriatric clinic model of care. Productivity outcomes included reports of cost-effectiveness, savings on transport, and improved waiting list metrics. Clinical benefits included successful polypharmacy reviews, and reductions in acute hospitalisation rates. Varying challenges were reported for both clinicians and patients in eight of the nine studies. Hearing impairments and difficulty with technology added to anxieties experienced by patients. Physicians missed the added value of a thorough physical examination and had concerns about confidentiality. CONCLUSION: Virtual geriatric clinics demonstrate evidence of productivity, benefit to patients, cost effectiveness and patient satisfaction with the treatment provided. In the current suboptimal pandemic climate, virtual geriatric clinics may allow Geriatricians to continue to provide an outpatient service, despite the encountered inherent challenges.

Association of Blood Pressure Lowering With Incident Dementia or Cognitive Impairment: A Systematic Review and Meta-analysis.

Importance: The benefit of blood pressure lowering for the prevention of dementia or cognitive impairment is unclear. Objective: To determine the association of blood pressure lowering with dementia or cognitive impairment. Data Sources and Study Selection: Search of PubMed, EMBASE, and CENTRAL for randomized clinical trials published from database inception through December 31, 2019, that evaluated the association of blood pressure lowering on cognitive outcomes. The control groups consisted of either placebo, alternative antihypertensive agents, or higher blood pressure targets. Data Extraction and Synthesis: Data were screened and extracted independently by 2 authors. Random-effects meta-analysis models were used to report pooled treatment effects and CIs. Main Outcomes and Measures: The primary outcome was dementia or cognitive impairment. The secondary outcomes were cognitive decline and changes in cognitive test scores. Results: Fourteen randomized clinical trials were eligible for inclusion (96 158 participants), of which 12 reported the incidence of dementia (or composite of dementia and cognitive impairment [3 trials]) on follow-up and were included in the primary meta-analysis, 8 reported cognitive decline, and 8 reported changes in cognitive test scores. The mean (SD) age of trial participants was 69 (5.4) years and 40 617 (42.2%) were women. The mean systolic baseline blood pressure was 154 (14.9) mm Hg and the mean diastolic blood pressure was 83.3 (9.9) mm Hg. The mean duration of follow-up was 49.2 months. Blood pressure lowering with antihypertensive agents compared with control was significantly associated with a reduced risk of dementia or cognitive impairment (12 trials; 92 135 participants) (7.0% vs 7.5% of patients over a mean trial follow-up of 4.1 years; odds ratio [OR], 0.93 [95% CI, 0.88-0.98]; absolute risk reduction, 0.39% [95% CI, 0.09%-0.68%]; I2 = 0.0%) and cognitive decline (8 trials) (20.2% vs 21.1% of participants over a mean trial follow-up of 4.1 years; OR, 0.93 [95% CI, 0.88-0.99]; absolute risk reduction, 0.71% [95% CI, 0.19%-1.2%]; I2 = 36.1%). Blood pressure lowering was not significantly associated with a change in cognitive test scores. Conclusions and Relevance: In this meta-analysis of randomized clinical trials, blood pressure lowering with antihypertensive agents compared with control was significantly associated with a lower risk of incident dementia or cognitive impairment.

Lipid Lowering Therapy, Low-Density Lipoprotein Level and Risk of Intracerebral Hemorrhage - A Meta-Analysis.

BACKGROUND: The association of lipid lowering therapy and intracerebral hemorrhage risk is controversial. METHODS: We performed a cumulative meta-analysis of lipid lowering trials that reported intracerebral hemorrhage. Statin, fibrate, ezetimibe, PCSK9, and CETP trials were included. We explored whether the association of lipid lowering therapy and risk of intracerebral hemorrhage may vary by baseline low-density lipoprotein (LDL) level, mean change in LDL or baseline cardiovascular risk of population. RESULTS: Among 39 trials (287,651 participants), lipid lowering therapy was not associated with a statistically significant increased risk of intracerebral hemorrhage (ICH) in primary and secondary prevention trials combined (odds ratio [OR], 1.12; 95% confidence interval [CI], .98-1.28). Lipid lowering was associated with an increased risk of ICH in secondary prevention trials (OR, 1.18; 95% CI, 1.00-1.38), but not in primary prevention trials (OR, 1.01; 95% CI, .78-1.30), but the test for interaction was not significant (P for interaction = .31). Meta-regression of baseline LDL or difference in LDL reduction between active and control did not explain significant heterogeneity between studies for ICH risk. Of 1000 individuals treated for 1 year for secondary prevention, we estimated 9.17 (95% CI, 5.78-12.66) fewer ischemic strokes and .48 (95% CI, .06-1.02) more ICH, and a net reduction of 8.69 in all stroke per 1000 person-years. CONCLUSIONS: The benefits of lipid lowering therapy in prevention of ischemic stroke greatly exceed the risk of ICH. Concern about ICH should not discourage stroke clinicians from prescribing lipid lowering therapy for secondary prevention of ischemic stroke.