Impact of COPD and anemia on motor and cognitive performance in the general older population: results from the English longitudinal study of ageing

Background: Cognitive and motor-performance decline with age and the process is accelerated by decline in general health. In this study, we aimed to estimate the effects of COPD and HB levels on cognitive and motor performance in the general older population and assess potential interaction. Methods: The English Longitudinal Study of Aging is a population-based cohort study including measurements of lung-function and HB levels together with cognitive and motor performance testing. Data were collected from 5709 participants including three measurement time over eight years. COPD was defined using lung-function-parameters and clinical symptoms. HB was assessed continuously and low HB was defined using clinical anemia cutoffs. Linear mixed-effects regression models were used to quantify the associations of COPD and HB with outcome measures, both individually and in combination. Results: Participants with both low HB and COPD demonstrated worse motor performance compared to individuals with only one exposure, resulting in up to 1 s (95%CI, 0.04–1.8) longer time needed to complete the five times sit to stand task than what would be expected based on purely additive effects. Additionally in individuals with COPD, the time to complete the motor-performance task per unit decrease in continuous HB levels was longer than in participants without COPD after full adjustment for confounding (up to 1.38 s/unit HB level, 95% CI: 0.65–2.11). Conclusion: In persons with COPD low HB levels may contribute to low motor-performance in a supra additive fashion. Further studies should re-evaluate whether earlier treatment of lower HB in these individuals might be beneficial

A Systematic Review

Background and Purpose Hypercoagulability increases the risk of arterial thrombosis; however, this effect may differ between various manifestations of arterial disease. Methods In this study, we compared the effect of coagulation factors as measures of hypercoagulability on the risk of ischaemic stroke (IS) and myocardial infarction (MI) by performing a systematic review of the literature. The effect of a risk factor on IS (relative risk for IS, RRIS) was compared with the effect on MI (RRMI) by calculating their ratio (RRR = RRIS/RRMI). A relevant differential effect was considered when RRR was >1+ its own standard error (SE) or <1−SE. Results We identified 70 publications, describing results from 31 study populations, accounting for 351 markers of hypercoagulability. The majority (203/351, 58%) had an RRR greater than 1. A larger effect on IS risk than MI risk (RRE>1+1SE) was found in 49/343 (14%) markers. Of these, 18/49 (37%) had an RRR greater than 1+2SE. On the opposite side, a larger effect on MI risk (RRR<1-1SE) was found in only 17/343 (5%) markers. Conclusions These results suggest that hypercoagulability has a more pronounced effect on the risk of IS than that of MI

Hypercoagulability and the risk of recurrence in young women with myocardial infarction or ischaemic stroke: a cohort study

Background: We aimed to investigate the role of hypercoagulability on the risk of lifetime cardiovascular recurrences after myocardial infarction or ischaemic stroke. Methods: Young women (< 50 years) with either myocardial infarction (n = 197) or ischaemic stroke (n = 107) were followed between 1995 and 2012 in the RATIO follow-up study. To determine whether hypercoagulability affects the risk or recurrence, a coagulation score based on acquired and inherited markers was compiled and used in a quartile analysis. Hazard ratios (HRs) obtained from Cox proportional models and adjusted for several cardiovascular risk factors were used to compare quartiles of the coagulation score for the risk of recurrence. Results: During a median follow-up of 19 years, 59 cardiovascular recurrences occurred. In patients with myocardial infarction no association was found between a high prothrombotic score and recurrences (highest quartile vs lowest quartile HR 0.7, 95% CI, 0.3–1.8). Conversely, ischaemic stroke patients with a high prothrombotic score showed a doubling in risk of long-term cardiovascular recurrences (HR 1.9, 95% CI 0.6–6.3) compared with ischaemic stroke patients and low levels of the score, with a dose response relationship. Conclusions: An increased coagulation tendency might be associated with long-term cardiovascular risk in women with ischaemic stroke, but not in women with myocardial infarction

Smoking Does Not Alter Treatment Effect of Intravenous Thrombolysis in Mild to Moderate Acute Ischemic Stroke—A Dutch String-of-Pearls Institute (PSI) Stroke Study

Background:The smoking-thrombolysis paradox refers to a better outcome in smokers who suffer from acute ischemic stroke (AIS) following treatment with thrombolysis. However, studies on this subject have yielded contradictory results and an interaction analysis of exposure to smoking and thrombolysis in a large, multicenter database is lacking. Methods:Consecutive AIS patients admitted within 12 h of symptom onset between 2009 and 2014 from the prospective, multicenter stroke registry (Dutch String-of-Pearls Stroke Study) were included for this analysis. We performed a generalized linear model for functional outcome 3 months post-stroke depending on risk of the exposure variables (smoking yes/no, thrombolysis yes/no). The following confounders were adjusted for: age, smoking, hypertension, atrial fibrillation, diabetes mellitus, stroke severity, and stroke etiology. Results:Out of 468 patients, 30.6% (N= 143) were smokers and median baseline NIHSS was 3 (interquartile range 1-6). Smoking alone had a crude and adjusted relative risk (RR) of 0.99 (95% CI 0.89-1.10) and 0.96 (95% CI 0.86-1.01) for good outcome (modified Rankin Score <= 2), respectively. A combination of exposure variables (smoking and thrombolysis) did not change the results significantly [crude RR 0.87 (95% CI 0.74-1.03], adjusted RR 1.1 (95%CI 0.90-1.30)]. Smoking alone had an adjusted RR of 1.2 (95% CI 0.6-2.7) for recanalization following thrombolysis (N= 88). Conclusions:In patients with mild to moderate AIS admitted within 12 h of symptom onset, smoking did not modify treatment effect of thrombolysis

Two simple and rapid methods based on maximum diameter accurately estimate large lesion volumes in acute stroke

Background: We compared two simple and rapid diameter-based methods (ABC/2, od-value) in terms of their accuracy in predicting lesion volume >70 ml and >100 ml. Methods: In 238 DWI images of ischemic stroke patients from the AXIS2 trial, maximum lesion diameter and corresponding maximum orthogonal diameter were measured. Estimation of infarct volume based on od-value and ABC/2 calculation was compared to volumetric assessments. Results: Accuracy of od-value and ABC/2 was similar for >70 ml (92.0 vs. 87.4) and >100 ml (92.9 vs. 93.3). ABC/2 overestimated lesion volume by 29.9%, resulting in a lower specificity. Conclusions: Od-value is a robust tool for patient selection in trials

Eight lessons from 2 years of use of the Post-COVID-19 Functional Status scale

Based on the literature and users’ experiences, lessons could be learned after 2 years’ use of the Post-COVID-19 Functional Status (PCFS) scale, that could contribute to its optimal use. All in all, the PCFS scale provided added value during the pandemic. https://bit.ly/3KkI5A

Early in-hospital exposure to statins and outcome after intracerebral haemorrhage – results from the Virtual International Stroke Trials Archive

Introduction: Recent data suggest that statin use after intracerebral haemorrhage might be beneficial. However, data on the effects of early in-hospital statin exposure are lacking. Therefore, we sought to assess whether (1) early statin exposure during the acute phase after intracerebral haemorrhage and (2) early continuation of prevalent statin use are associated with favourable functional outcome. Patients and methods: Data were obtained from the Virtual International Stroke Trials Archive. Patients were categorised according to use patterns of statins during this early in-hospital phase (continuation, discontinuation or new initiation of statins). Univariate and multivariable analyses were conducted to explore the association between early statin exposure and functional outcome. Results: A total of 919 patients were included in the analysis. Early in-hospital statin exposure (n = 89, 9.7%) was associated with better functional outcome (modified Rankin Scale ≤ 3) compared with 790 patients without statin exposure before or early after the event (66% versus 47%, adjusted OR 2.1, 95% confidence interval 1.3–3.6).  Compared with patients without exposure to statins before and early after the event, early continuation of statin therapy (n = 57) was associated with favourable functional outcome (adjusted odds ratio 2.6, 95% confidence interval 1.3–5.2). The association between early continuation of statins and outcome remained robust in sensitivity analyses restricted to patients able to take oral medication within 72 h and one-week survivors. Discussion: It is possible that part of the observed associations are not due to a protective effect of statins but are confounded by indication bias. Conclusion: Statin exposure and continuation of prevalent statin therapy early after intracerebral haemorrhage are associated with favourable functional outcome after 90 days

Prognostication after intracerebral hemorrhage: a review

Background Approximately half of patients with spontaneous intracerebral hemorrhage (ICH) die within 1 year. Prognostication in this context is of great importance, to guide goals of care discussions, clinical decision-making, and risk stratification. However, available prognostic scores are hardly used in clinical practice. The purpose of this review article is to identify existing outcome prediction scores for spontaneous intracerebral hemorrhage (ICH) discuss their shortcomings, and to suggest how to create and validate more useful scores. Main text Through a literature review this article identifies existing ICH outcome prediction models. Using the Essen-ICH-score as an example, we demonstrate a complete score validation including discrimination, calibration and net benefit calculations. Score performance is illustrated in the Erlangen UKER-ICH-cohort (NCT03183167). We identified 19 prediction scores, half of which used mortality as endpoint, the remainder used disability, typically the dichotomized modified Rankin score assessed at variable time points after the index ICH. Complete score validation by our criteria was only available for the max-ICH score. Our validation of the Essen-ICH-score regarding prediction of unfavorable outcome showed good discrimination (area under the curve 0.87), fair calibration (calibration intercept 1.0, slope 0.84), and an overall net benefit of using the score as a decision tool. We discuss methodological pitfalls of prediction scores, e.g. the withdrawal of care (WOC) bias, physiological predictor variables that are often neglected by authors of clinical scores, and incomplete score validation. Future scores need to integrate new predictor variables, patient-reported outcome measures, and reduce the WOC bias. Validation needs to be standardized and thorough. Lastly, we discuss the integration of current ICH scoring systems in clinical practice with the awareness of their shortcomings. Conclusion Presently available prognostic scores for ICH do not fulfill essential quality standards. Novel prognostic scores need to be developed to inform the design of research studies and improve clinical care in patients with ICH

Increasing efficiency of preclinical research by group sequential designs.

Despite the potential benefits of sequential designs, studies evaluating treatments or experimental manipulations in preclinical experimental biomedicine almost exclusively use classical block designs. Our aim with this article is to bring the existing methodology of group sequential designs to the attention of researchers in the preclinical field and to clearly illustrate its potential utility. Group sequential designs can offer higher efficiency than traditional methods and are increasingly used in clinical trials. Using simulation of data, we demonstrate that group sequential designs have the potential to improve the efficiency of experimental studies, even when sample sizes are very small, as is currently prevalent in preclinical experimental biomedicine. When simulating data with a large effect size of d = 1 and a sample size of n = 18 per group, sequential frequentist analysis consumes in the long run only around 80% of the planned number of experimental units. In larger trials (n = 36 per group), additional stopping rules for futility lead to the saving of resources of up to 30% compared to block designs. We argue that these savings should be invested to increase sample sizes and hence power, since the currently underpowered experiments in preclinical biomedicine are a major threat to the value and predictiveness in this research domain.German Federal Ministry of Education and Research (BMBF) www.bmbf.de (grant number 01EO1301)

Coagulation factor VIII, white matter hyperintensities and cognitive function: Results from the Cardiovascular Health Study

Objective: To investigate the relationship between high FVIII clotting activity (FVIII:C), MRI-defined white matter hyperintensities (WMH) and cognitive function over time. Methods: Data from the population-based Cardiovascular Health Study (n = 5,888, aged ≥ 65) were used. FVIII:C was measured in blood samples taken at baseline. WMH burden was assessed on two cranial MRI scans taken roughly 5 years apart. Cognitive function was assessed annually using the Modified Mini-Mental State Examination (3MSE) and Digit Symbol Substitution Test (DSST). We used ordinal logistic regression models adjusted for demographic and cardiovascular factors in cross-sectional and longitudinal WMH analyses, and adjusted linear regression and linear mixed models in the analyses of cognitive function. Results: After adjustment for confounding, higher levels of FVIII:C were not strongly associated with the burden of WMH on the initial MRI scan (OR>p75 = 1.20, 95% CI 0.99-1.45; N = 2,735) nor with WMH burden worsening over time (OR>p75 = 1.18, 95% CI 0.87-1.59; N = 1,527). High FVIII:C showed no strong association with cognitive scores cross-sectionally (3MSE>p75 β = -0.06, 95%CI -0.45 to 0.32, N = 4,005; DSST>p75 β = -0.69, 95%CI -1.52 to 0.13, N = 3,954) or over time (3MSE>p75 β = -0.07,95% CI -0.58 to 0.44, N = 2,764; DSST>p75 β = -0.22, 95% CI -0.97 to 0.53, N = 2,306) after confounding adjustment. Interpretation: The results from this cohort study of older adult participants indicate no strong relationships between higher FVIII:C levels and WMH burden or cognitive function in cross-sectional and longitudinal analyses