Long-term follow-up of cognitive function and activities of daily living in older people: a feasibility study in the PROSPER cohort

<p>Background: The Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) considered the benefits of pravastatin therapy and provided insights into cognitive decline/disability in older people but follow-up was short.</p> <p>Methods: We performed a feasibility study of 300 PROSPER recruits, 7 years after the trial finished. The subject’s general practitioner provided basic follow-up data. Telephone contact with participants established cognition/functional level. Relatives of those unsuitable for contact were asked to complete postal questionnaires.</p> <p>Results: Of 300 participants we established 132 were alive, 135 dead and 33 lost to follow-up. Of 132 survivors data were obtained for 78 participants by telephone, 10 participants with GP diagnosis of dementia, and 3 participants whose relative provided information. Therefore cognitive function was determined in 69% of survivors and functional ability in 61%.</p> <p>Conclusions: It was feasible to perform long-term follow-up of cognition/functional ability in the majority of survivors from a large randomised controlled trial.</p&gt

Hemostatic function and progressing ischemic stroke: D-dimer predicts early clinical progression

<p><b>Background and Purpose:</b> Early clinical progression of ischemic stroke is common and is associated with increased risk of death and dependency. We hypothesized that activation of the coagulation system is an important contributor in some cases of deterioration. We aimed to characterize alterations in circulating hemostatic markers in patients with progressing stroke.</p> <p><b>Methods:</b> Consecutive acute ischemic stroke admissions were recruited. Progressing stroke was defined by deterioration in components of the Scandinavian Stroke Scale. Hemostatic markers (coagulation factors VIIc, VIIIc, and IXc, prothrombin fragments 1+2 [F1+2], thrombin-antithrombin complexes [TAT], D- dimer, fibrinogen, von Willebrand factor [vWF] and tissue plasminogen activator) were measured within 24 hours of symptom recognition.</p> <p><b>Results:</b> Fifty-four (25%) of the 219 patients met criteria for progressing stroke. F1+2 (median 1.28 versus 1.06 nmol/L, P=0.01), TAT (5.28 versus 4.07 mug/L, P lt 0.01), D-dimer ( 443 versus 194 ng/mL, P lt 0.001) and vWF (216 versus 198 IU/dL, P lt 0.05) levels were higher in these patients than in stable/improving patients. In logistic regression analysis, with all important clinical and laboratory variables included, only natural log D-dimer (odds ratio [OR]: 1.87; 95% confidence interval [CI]: 1.38 to 2.54; P=0.0001) and mean arterial blood pressure (OR: 1.26 per 10 mm Hg change; 95% CI: 1.05 to 1.51; P=0.01) remained independent predictors of progressing stroke.</p> <p><b>Conclusions:</b> There is evidence of excess thrombin generation and fibrin turnover in patients with progressing ischemic stroke. Measurement of D-dimer levels can identify patients at high risk for stroke progression. Further research is required to determine whether such patients benefit from acute interventions aimed at modifying hemostatic function.</p&gt

Systems approaches to animal disease surveillance and resource allocation: methodological frameworks for behavioral analysis

While demands for animal disease surveillance systems are growing, there has been little applied research that has examined the interactions between resource allocation, cost-effectiveness, and behavioral considerations of actors throughout the livestock supply chain in a surveillance system context. These interactions are important as feedbacks between surveillance decisions and disease evolution may be modulated by their contextual drivers, influencing the cost-effectiveness of a given surveillance system. This paper identifies a number of key behavioral aspects involved in animal health surveillance systems and reviews some novel methodologies for their analysis. A generic framework for analysis is discussed, with exemplar results provided to demonstrate the utility of such an approach in guiding better disease control and surveillance decisions

Risk factors for chest infection in acute stroke: a prospective cohort study

<p><b>Background and Purpose:</b> Pneumonia is a major cause of morbidity and mortality after stroke. We aimed to determine key characteristics that would allow prediction of those patients who are at highest risk for poststroke pneumonia.</p> <p><b>Methods:</b> We studied a series of consecutive patients with acute stroke who were admitted to hospital. Detailed evaluation included the modified National Institutes of Health Stroke Scale; the Abbreviated Mental Test; and measures of swallow, respiratory, and oral health status. Pneumonia was diagnosed by set criteria. Patients were followed up at 3 months after stroke.</p> <p><b>Results:</b> We studied 412 patients, 391 (94.9%) with ischemic stroke and 21 (5.1%) with hemorrhagic stroke; 78 (18.9%) met the study criteria for pneumonia. Subjects who developed pneumonia were older (mean±SD age, 75.9±11.4 vs 64.9±13.9 years), had higher modified National Institutes of Health Stroke Scale scores, a history of chronic obstructive pulmonary disease, lower Abbreviated Mental Test scores, and a higher oral cavity score, and a greater proportion tested positive for bacterial cultures from oral swabs. In binary logistic-regression analysis, independent predictors (P<0.05) of pneumonia were age >65 years, dysarthria or no speech due to aphasia, a modified Rankin Scale score ≥4, an Abbreviated Mental Test score <8, and failure on the water swallow test. The presence of 2 or more of these risk factors carried 90.9% sensitivity and 75.6% specificity for the development of pneumonia.</p> <p><b>Conclusions:</b> Pneumonia after stroke is associated with older age, dysarthria/no speech due to aphasia, severity of poststroke disability, cognitive impairment, and an abnormal water swallow test result. Simple assessment of these variables could be used to identify patients at high risk of developing pneumonia after stroke.</p&gt

Effect of statins on atrial fibrillation: collaborative meta-analysis of published and unpublished evidence from randomised controlled trials

Objective To examine whether statins can reduce the risk of atrial fibrillation. Design Meta-analysis of published and unpublished results from larger scale statin trials, with comparison of the findings against the published results from smaller scale or shorter duration studies. Data sources Medline, Embase, and Cochrane's CENTRAL up to October 2010. Unpublished data from longer term trials were obtained through contact with investigators. Study selection Randomised controlled trials comparing statin with no statin or comparing high dose versus standard dose statin; all longer term trials had at least 100 participants and at least six months' follow-up. Results In published data from 13 short term trials (4414 randomised patients, 659 events), statin treatment seemed to reduce the odds of an episode of atrial fibrillation by 39% (odds ratio 0.61, 95% confidence interval 0.51 to 0.74; P<0.001), but there was significant heterogeneity (P<0.001) between the trials. In contrast, among 22 longer term and mostly larger trials of statin versus control (105 791 randomised patients, 2535 events), statin treatment was not associated with a significant reduction in atrial fibrillation (0.95, 0.88 to 1.03; P=0.24) (P<0.001 for test of difference between the two sets of trials). Seven longer term trials of more intensive versus standard statin regimens (28 964 randomised patients and 1419 events) also showed no evidence of a reduction in the risk of atrial fibrillation (1.00, 0.90 to 1.12; P=0.99). Conclusions The suggested beneficial effect of statins on atrial fibrillation from published shorter term studies is not supported by a comprehensive review of published and unpublished evidence from larger scale trials

Circulating interleukin-10 and risk of cardiovascular events: a prospective study in the elderly at risk

<p><b>Objective:</b> The goal of this study was to examine the association of the antiinflammatory interleukin-10 (IL-10) with risk of cardiovascular disease (CVD).</p> <p><b>Methods and Results:</b> In the PROSPER (PROspective Study of Pravastatin in the Elderly at Risk) cohort, we related baseline concentrations of circulating IL-10 to risk of CVD events in a nested case (n=819)-control (n=1618) study of 3.2 years of follow-up. Circulating IL-10 showed few strong associations with classical risk factors but was positively correlated with IL-6 and C-reactive protein. IL-10 was positively associated with risk of CVD events (odds ratio [OR] 1.17, 95% CI 1.05 to 1.31 per unit increase in log IL-10) after adjusting for classical risk factors and C-reactive protein. Furthermore, IL-10 was associated more strongly with CVD risk among those with no previous history of CVD (OR 1.42, 95% CI 1.18 to 1.70), compared with those with previous CVD (OR 1.04, 95% CI 0.90 to 1.19; P=0.018). Overall, IL-10 showed a modest ability to add discrimination to classical risk factors (C-statistic +0.005, P=0.002).</p> <p><b>Conclusion:</b> Baseline circulating levels of the antiinflammatory IL-10 are positively associated with risk of CVD among the elderly without prior CVD events, although the association is less evident in those with a history of CVD. Additional epidemiological and mechanistic studies investigating the role of IL-10 in CVD are warranted.</p&gt

Homocysteine levels and treatment effect in the prospective study of pravastatin in the elderly at risk

Objectives: To assess the effect of preventive pravastatin treatment on coronary heart disease (CHD) morbidity and mortality in older persons at risk for cardiovascular disease (CVD), stratified according to plasma levels of homocysteine.<p></p> Design: A post hoc subanalysis in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER), started in 1997, which is a double-blind, randomized, placebo-controlled trial with a mean follow-up of 3.2 years.<p></p> Setting: Primary care setting in two of the three PROSPER study sites (Netherlands and Scotland).<p></p> Participants: Individuals (n = 3,522, aged 70–82, 1,765 male) with a history of or risk factors for CVD were ranked in three groups depending on baseline homocysteine level, sex, and study site.<p></p> Intervention: Pravastatin (40 mg) versus placebo.<p></p> Measurements: Fatal and nonfatal CHD and mortality.<p></p> Results: In the placebo group, participants with a high homocysteine level (n = 588) had a 1.8 higher risk (95% confidence interval (CI) = 1.2–2.5, P = .001) of fatal and nonfatal CHD than those with a low homocysteine level (n = 597). The absolute risk reduction in fatal and nonfatal CHD with pravastatin treatment was 1.6% (95% CI = −1.6 to 4.7%) in the low homocysteine group and 6.7% (95% CI = 2.7–10.7%) in the high homocysteine group (difference 5.2%, 95% CI = 0.11–10.3, P = .046). Therefore, the number needed to treat (NNT) with pravastatin for 3.2 years for benefit related to fatal and nonfatal CHD events was 14.8 (95% CI = 9.3–36.6) for high homocysteine and 64.5 (95% CI = 21.4–∞) for low homocysteine.<p></p> Conclusion: In older persons at risk of CVD, those with high homocysteine are at highest risk for fatal and nonfatal CHD. With pravastatin treatment, this group has the highest absolute risk reduction and the lowest NNT to prevent fatal and nonfatal CHD.<p></p&gt

Association of complement receptor 1 gene polymorphisms with cognitive function

Previous evidence suggest involvement of the complement receptor 1 (CR1) in development of Alzheimer’s disease. We investigated the association of CR1 gene polymorphisms with cognitive function in older subjects. Single nucleotide polymorphisms (SNPs) within the CR1 region on chromosome 1 (n = 73) were assessed in 5,244 participants in the PROspective Study of Pravastatin in the Elderly at Risk (51.9% female, mean age 75.3 yr). Linear regression, adjusted for age, sex, country, and use of pravastatin, was used to assess the association between the SNPs and cognitive function. All 73 SNPs within the genomic region of the CR1 gene on chromosome 1 were extracted. Eighteen were independent, according to a relatively stringent R2 threshold of >0.8 with LDlink. Twelve of the 18 investigated CR1 SNPs were significantly associated with a decline in cognitive function (all P < 0.05). These data indicate that genetic variation within the CR1 gene is associated not only with Alzheimer’s disease, but also with general cognitive function during late life

Comprehensive Geriatric Assessment in hospital and hospital-at-home settings: a mixed-methods study

Background: The Comprehensive Geriatric Assessment (CGA) is a multidisciplinary process that determines a frail older person’s medical, functional, psychological and social capability to ensure that they have a co-ordinated plan for treatment and follow-up. Objectives: To improve our understanding of the effectiveness, cost-effectiveness and implementation of the CGA across hospital and hospital-at-home settings. Methods: We used a variety of methods. We updated a Cochrane review of randomised trials of the CGA in hospital for older people aged ≥ 65 years, conducted a national survey of community CGA, analysed data from three health boards using propensity score matching (PSM) and regression analysis, conducted a qualitative study and used a modified Delphi method. Results: We included 29 trials recruiting 13,766 participants in the Cochrane review of the CGA. Older people admitted to hospital who receive the CGA are more likely to be living at home at 3–12 months’ follow-up [relative risk (RR) 1.06, 95% confidence interval (CI) 1.01 to 1.10] (high certainty). The probability that the CGA would be cost-effective at a £20,000 ceiling ratio for quality-adjusted life-years (QALYs), life-years (LYs) and LYs living at home was 0.50, 0.89, and 0.47, respectively (low-certainty evidence). After PSM and regression analysis comparing CGA hospital with CGA hospital at home, we found that the health-care cost (from admission to 6 months after discharge) in site 1 was lower in hospital at home (ratio of means 0.82, 95% CI 0.76 to 0.89), in site 2 there was little difference (ratio of means 1.00, 95% CI 0.92 to 1.09) and in site 3 it was higher (ratio of means 1.15, 95% CI 0.99 to 1.33). Six months after discharge (excluding the index admission), the ratio of means cost in site 1 was 1.27 (95% CI 1.14 to 1.41), in site 2 was 1.09 (95% CI 0.95 to 1.24) and in site 3 was 1.70 (95% CI 1.40 to 2.07). At 6 months’ follow-up (excluding the index admission), there may be an increased risk of mortality (adjusted) in the three hospital-at-home cohorts (site 1: RR 1.09, 95% CI 1.00 to 1.19; site 2: RR 1.29, 95% CI 1.15 to 1.44; site 3: RR 1.27, 95% CI 1.06 to 1.54). The qualitative research indicates the importance of relational aspects of health care, incorporating caregivers’ knowledge in care planning, and a lack of clarity about the end of an episode of health care. Core components that should be included in CGA focus on functional, physical and mental well-being, medication review and a caregiver’s ability to care. Limitations: The risk of residual confounding limits the certainty of the findings from the PSM analysis; a second major limitation is that the research plan did not include an investigation of social care or primary care. Conclusions: The CGA is an effective way to organise health care for older people in hospital and may lead to a small increase in costs. There may be an increase in cost and the risk of mortality in the population who received the CGA hospital at home compared with those who received the CGA in hospital; randomised evidence is required to confirm or refute this. Caregiver involvement in the CGA process could be strengthened. Funding: The National Institute for Health Research Health Services and Delivery Research programme