Raphae S. Barlas

Impact of Hemoglobin Levels and Anemia on Mortality in Acute Stroke: Analysis of UK Regional Registry Data, Systematic Review, and Meta‐Analysis

Background The impact of hemoglobin levels and anemia on stroke mortality remains controversial. We aimed to systematically assess this association and quantify the evidence. Methods and Results We analyzed data from a cohort of 8013 stroke patients (mean±SD, 77.81±11.83 years) consecutively admitted over 11 years (January 2003 to May 2015) using a UK Regional Stroke Register. The impact of hemoglobin levels and anemia on mortality was assessed by sex‐specific values at different time points (7 and 14 days; 1, 3, and 6 months; 1 year) using multiple regression models controlling for confounders. Anemia was present in 24.5% of the cohort on admission and was associated with increased odds of mortality at most of the time points examined up to 1 year following stroke. The association was less consistent for men with hemorrhagic stroke. Elevated hemoglobin was also associated with increased mortality, mainly within the first month. We then conducted a systematic review using the Embase and Medline databases. Twenty studies met the inclusion criteria. When combined with the cohort from the current study, the pooled population had 29 943 patients with stroke. The evidence base was quantified in a meta‐analysis. Anemia on admission was found to be associated with an increased risk of mortality in both ischemic stroke (8 studies; odds ratio 1.97 [95% CI 1.57–2.47]) and hemorrhagic stroke (4 studies; odds ratio 1.46 [95% CI 1.23–1.74]). Conclusions Strong evidence suggests that patients with anemia have increased mortality with stroke. Targeted interventions in this patient population may improve outcomes and require further evaluation.

Impact of stroke-associated pneumonia on mortality, length of hospitalization and functional outcome

Stroke‐associated pneumonia (SAP) is common and associated with adverse outcomes. Data on its impact beyond 1 year are scarce.

Addition of sodium criterion to SOAR stroke score.

To examine the usefulness of including sodium (Na) levels as a criterion to the SOAR stroke score in predicting inpatient and 7‐day mortality in stroke.

Rural dwellers are less likely to survive cancer – An international review and meta-analysis

Background: Existing research from several countries has suggested that rural‐dwellers may have poorer cancer survival than urban‐dwellers. However, to date, the global literature has not been systematically reviewed to determine whether a rural cancer survival disadvantage is a global phenomenon. Methods: Medline, CINAHL, and EMBASE were searched for studies comparing rural and urban cancer survival. At least two authors independently screened and selected studies. We included epidemiological studies comparing cancer survival between urban and rural residents (however defined) that also took socioeconomic status into account. A meta‐analysis was conducted using 11 studies with binary rural:urban classifications to determine the magnitude and direction of the association between rurality and differences in cancer survival. The mechanisms for urban‐rural cancer survival differences reported were narratively synthesised in all 39 studies. Findings: 39 studies were included in this review. All were retrospective observational studies conducted in developed countries. Rural‐dwellers were significantly more likely to die when they developed cancer compared to urban‐dwellers (HR 1.05 (95% CI 1.02 – 1.07). Potential mechanisms were aggregated into an ecological model under the following themes: Patient Level Characteristics; Institutions; Community, Culture and Environment; Policy and Service Organization. Interpretation: Rural residents were 5% less likely to survive cancer. This effect was consistently observed across studies conducted in various geographical regions and using multiple definitions of rurality. High quality mixed‐methods research is required to comprehensively evaluate the underlying factors. We have proposed an ecological model to provide a coherent framework for future explanatory research. Funding: None. HIGHLIGHTSRetrospective observational studies conducted in developed countries comparing urban and rural cancer survival and related outcomes.Increased risk in cancer death among rural/remote patients.Establishment of a theoretical framework to illustrate factors influencing cancer survival in these geographical regions.Support for further research on these themes.

Long-Term Factors Associated With Falls and Fractures Poststroke

Background Risk factors for poststroke falls and fractures remain poorly understood. This study aimed to evaluate which factors increased risk of these events after stroke. Methods Data from 7,267 hospitalized stroke patients were acquired from the Norfolk and Norwich University Hospital Stroke Register from 2003–2015. The impacts of multiple patient level and stroke characteristics and comorbidities on post-discharge falls and fractures were assessed. Univariate and multivariable models were constructed, adjusting for multiple confounders, using binary logistic regression for short-term analysis (up to 1-year post-discharge) and Cox-proportional hazard models for longer term analysis (1–3, 3–5, and 0–10 years follow-up). Results The mean age (SD) was 76.3 ± 12.1 years at baseline. 1,138 (15.7%) participants had an incident fall; and 666 (9.2%) an incident fracture during the 10-year follow-up (total person years = 64,447.99 for falls and 67,726.70 for fractures). Half of the sample population were females (50.6%) and the majority had an ischemic stroke (89.8%). After adjusting for confounders: age, sex, previous history of falls, and atrial fibrillation were associated with an increased risk of both falls and fractures during follow-up. Furthermore, chronic kidney disease and hyperlipidemia were associated with an increased risk of falls, while previous stroke/transient ischemic attack increased fracture risk. Total anterior circulation stroke and a prestroke modified Rankin Scale score of 3–5 were associated with decreased risk of both events, with hypertension and cancer decreasing risk of falls only. Conclusion We identified demographic, stroke-related, and comorbid factors associated with poststroke falls and fracture incidence. Further studies are required to examine and establish the relationship between reversible factors and further explore the role of preventative measures to prevent poststroke falls and fractures.

Effect of Antiplatelet Therapy (Aspirin + Dipyridamole Versus Clopidogrel) on Mortality Outcome in Ischemic Stroke

The optimal regimen of antiplatelet therapy for secondary prevention in noncardioembolic ischemic stroke remains controversial. We aimed to determine which regimen was associated with the greatest reduction in adverse outcomes. We analysed prospectively collected data from the Norfolk and Norwich University Hospital Stroke Register. The sample population consisted of 3,572 participants (mean age 74.96 ± 12.67) with ischemic stroke, who were consecutively admitted between 2003 and 2015. Patients were placed on one of three antiplatelet regimens at hospital discharge; aspirin monotherapy, aspirin plus dipyridamole and clopidogrel. Clopidogrel and aspirin plus dipyridamole were compared to aspirin. A direct comparison between clopidogrel and aspirin plus dipyridamole was also performed. Outcomes included all-cause mortality and a combined end point of all-cause mortality and incidence of major adverse cardiac events (stroke or myocardial infarction). Cox-regression models adjusted for potential confounders at the following time periods after discharge; 0 to 90 days, 91 to 365 days, and 1 to 3 years. Aspirin plus dipyridamole was associated with a lower risk of mortality at 0 to 90 days; hazard ratio (HR) 0.62 (0.43 to 0.91). Clopidogrel was associated with a lower risk of mortality at 1 to 3 years; HR of 0.39 (0.26 to 0.60). Similar HRs were observed for the corresponding time points in the composite outcome. In conclusion, patients with noncardioembolic stroke may gain maximum benefits from aspirin plus dipyridamole initially (≤1 year) with a subsequent switch to clopidogrel, with regard to mortality and major adverse cardiac eventsoutcomes.

Impact of anaemia on acute stroke outcomes depends on the type of anaemia: Evidence from a UK stroke register

BACKGROUND Previous research has demonstrated an association between anaemia and poor outcomes in acute stroke. This study aimed to assess the impact of anaemia on stroke by anaemia subtype. METHODS Data from a prospective UK Regional Stroke Register were used to assess the association between hypochromic microcytic and normochromic normocytic anaemia on inpatient-mortality, length of stay (LOS) and discharge modified Rankin scale (mRS). Analysis was stratified by stroke subtypes and multivariable logistic regression, adjusting for potential confounders, was used to quantify this association. Patients who were not anaemic were the reference category. RESULTS A total of 8167 stroke patients (admitted between 2003 and 2015) were included, mean age (SD) 77.39±11.90years. Of these, 3.4% (n=281) had hypochromic microcytic anaemia and 15.5% (n=1262) had normochromic normocytic anaemia on admission. Normochromic normocytic anaemia was associated with increased odds of in-patient mortality OR 1.48 (1.24-1.77), 90-day mortality OR 1.63 (1.38-1.92), longer LOS OR 1.21 (1.06-1.40), defined as >7days, and severe disability defined as discharge mRS≥3 OR 1.31 (1.06-1.63), in patients with ischaemic stroke. Hypochromic microcytic anaemia was associated with 90-day mortality OR 1.90 (1.40-2.58) and a longer LOS OR 1.57 (1.20-2.05) in patients with ischaemic stroke. CONCLUSIONS Hypochromic microcytic and normochromic normocytic anaemia are associated with differing outcomes in terms of inpatient mortality and post stroke disability. While it is unclear if anaemia per se or another underlying cause is responsible for adverse outcomes, subtype of anaemia appears to be relevant in stroke prognosis.

A History of Falls is Associated with a Significant Increase in Acute Mortality in Women after Stroke

Background and Purpose The risks of falls and fractures increase after stroke. Little is known about the prognostic significance of previous falls and fractures after stroke. This study examined whether having a history of either event is associated with poststroke mortality. Methods We analyzed stroke register data collected prospectively between 2003 and 2015. Eight sex-specific models were analyzed, to which the following variables were incrementally added to examine their potential confounding effects: age, type of stroke, Oxfordshire Community Stroke Project classification, previous comorbidities, frailty as indicated by the prestroke modified Rankin Scale score, and acute illness parameters. Logistic regression was applied to investigate in-hospital and 30-day mortality, and Cox proportional-hazards models were applied to investigate longer-term outcomes of mortality. Results In total, 10,477 patients with stroke (86.1% ischemic) were included in the analysis. They were aged 77.7±11.9 years (mean±SD), and 52.2% were women. A history of falls was present in 8.6% of the men (n=430) and 20.2% of the women (n=1,105), while 3.8% (n=189) of the men and 12.9% of the women (n=706) had a history of both falls and fractures. Of the outcomes examined, a history of falls alone was associated with increased in-hospital mortality [odds ratio (OR)=1.33, 95% confidence interval (CI)=1.03–1.71] and 30-day mortality (OR=1.34, 95% CI=1.03–1.73) in women in the fully adjusted models. The Cox proportional-hazards models for longer-term outcomes and the history of falls and fractures combined showed no significant results. Conclusions The history of falls is an important factor for acute stroke mortality in women. A previous history of falls may therefore be an important factor to consider in the short-term stroke prognosis, particularly in women.

Rheumatic mitral valve disease is associated with worse outcomes in stroke:A Thailand National Database Study

Background and Purpose— Rheumatic valvular heart disease is associated with the increased risk of cerebrovascular events, although there are limited data on the prognosis of patients with rheumatic mitral valve disease (RMVD) after stroke. Methods— We examined the association between RMVD and both serious and common cardiovascular and noncardiovascular (respiratory and infective) complications in a cohort of hospitalized stroke patients based in Thailand. Factors associated with in-hospital mortality were also explored. Data were obtained from a National Insurance Database. All hospitalized strokes between October 1, 2004, and January 31, 2013, were included in the current study. Characteristics and outcomes were compared for RMVD and non-RMVD patients. Logistic regression, propensity score matching, and multivariate models were used to assess study outcomes. Results— In total, 594 681 patients (mean [SD] age=64 [14.5] years) with a diagnosis of stroke (ischemic=306 154; hemorrhagic=195 392; undetermined=93 135) were included in this study, of whom 5461 had RMVD. Results from primary analyses showed that after ischemic stroke, and controlling for potential confounding covariates, RMVD was associated (P<0.001) with increased odds for cardiac arrest (odds ratio [95% confidence interval]=2.13 [1.68–2.70]), shock (2.13 [1.64–2.77]), arrhythmias (1.70 [1.21–2.39]), respiratory failure (2.09 [1.87–2.33]), pneumonia (2.00 [1.81–2.20]), and sepsis (1.39 [1.19–1.63]). In hemorrhagic stroke patients, RMVD was associated with increased odds (fully adjusted model) for respiratory failure (1.26 [1.01–1.57]), and in patients with undetermined stroke, RMVD was associated with increased odds (fully adjusted analyses) for shock (3.00 [1.46–6.14]), respiratory failure (2.70 [1.91–3.79]), and pneumonia (2.42 [1.88–3.11]). Conclusions— RMVD is associated with the development of cardiac arrest, shock, arrhythmias, respiratory failure, pneumonia, and sepsis after acute stroke.

Fatty acid-binding proteins as diagnostic and prognostic markers in pneumonia

Pneumonia remains a potentially life threatening infection. The incidence of community acquired pneumonia (CAP) differs by region, season and the characteristics of the population under evaluation. A recent review on CAP among adults in Europe found the incidence ranged from 1.54 to 1.70 per 1,000 population, rising to as high as 14.0 cases per 1,000 person-years in those aged 65 years and over (1). Mortality for patients hospitalised with CAP ranges from 5.1–36.5%. The mortality is particularly high in critically ill patients with pneumonia who require admission to intensive care units (ICUs) and reported figure is as high as 57.3% (2).