Estimated glomerular filtration rate and risk of poor outcomes after stroke.

BACKGROUND AND PURPOSE: The relationship of the estimated glomerular filtration rate (eGFR) with complications after stroke has not been fully characterized for the entire clinical spectrum of eGFR and for the fluctuation in eGFR during hospital stay. METHODS: Data from the Norfolk and Norwich Stroke Registry recorded between January 2003 and April 2015 were analysed. eGFR was categorized into six clinically relevant categories as per the Kidney Disease Improving Global Outcomes guidelines. The change in eGFR during acute admission was categorized into the following: within 5% change (reference), 5%-20% decline, >20% decline, 5%-20% increase and >20% increase. All-cause mortality, recurrent stroke, incident myocardial infarction, prolonged hospital stay and stroke disability at discharge were outcomes of interest. RESULTS: In all, 10 329 stroke patients (mean age 77.8 years) were followed for a mean of 2.9 years (30 126 person-years). Multivariable adjusted hazard ratios (95% confidence interval) for all-cause mortality were 0.91 (0.80-1.04), 0.96 (0.83-1.11), 1.23 (1.06-1.43), 1.54 (1.31-1.82) and 2.38 (1.91-2.97) for eGFR levels 60-89, 45-59, 30-44, 15-29 and <15 respectively, compared to eGFR ≥ 90 ml/min/1.73 m2 . The hazard ratios (95% confidence interval) for eGFR change were 1.56 (1.36-1.79), 1.17 (1.05-1.30), 1.47 (1.32-1.62) and 1.71 (1.55-1.88) for >20% decline, 5%-20% decline, 5%-20% increase and >20% increase, respectively, compared to change within 5%. Results were similar for other outcomes except recurrent stroke. CONCLUSIONS: Stroke patients with eGFR < 45 ml/min/1.73 m2 at hospital admission and >5% decline or increase in eGFR during hospital stay were at substantially higher risk of poor outcomes, particularly all-cause mortality, myocardial infarction, prolonged hospital stay and disability at discharge.

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

OBJECTIVES: Stroke-associated pneumonia (SAP) is common and associated with adverse outcomes. Data on its impact beyond 1 year are scarce. MATERIALS AND METHODS: This observational study was conducted in a cohort of stroke patients admitted consecutively to a tertiary referral center in the east of England, UK (January 2003-April 2015). Logistic regression models examined inpatient mortality and length of stay (LOS). Cox regression models examined longer-term mortality at predefined time periods (0-90 days, 90 days-1 year, 1-3 years, and 3-10 years) for SAP. Effect of SAP on functional outcome at discharge was assessed using logistic regression. RESULTS: A total of 9238 patients (mean age [±SD] 77.61 ± 11.88 years) were included. SAP was diagnosed in 1083 (11.7%) patients. The majority of these cases (n = 658; 60.8%) were aspiration pneumonia. After controlling for age, sex, stroke type, Oxfordshire Community Stroke Project (OCSP) classification, prestroke modified Rankin scale, comorbidities, and acute illness markers, mortality estimates remained significant at 3 time periods: inpatient (OR 5.87, 95%CI [4.97-6.93]), 0-90 days (2.17 [1.97-2.40]), and 91-365 days (HR 1.31 [1.03-1.67]). SAP was also associated with higher odds of long LOS (OR 1.93 [1.67-2.22]) and worse functional outcome (OR 7.17 [5.44-9.45]). In this cohort, SAP did not increase mortality risk beyond 1 year post-stroke, but it was associated with reduced mortality beyond 3 years. CONCLUSIONS: Stroke-associated pneumonia is not associated with increased long-term mortality, but it is linked with increased mortality up to 1 year, prolonged LOS, and poor functional outcome on discharge. Targeted intervention strategies are required to improve outcomes of SAP patients who survive to hospital discharge.

Addition of sodium criterion to SOAR stroke score.

OBJECTIVES: 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. MATERIALS AND METHODS: Data from the Norfolk and Norwich University Hospital Stroke & TIA register (2003-2015) were analysed. Univariate and then multivariate models controlling for SOAR variables were used to assess the association between admission sodium levels and inpatient and 7-day mortality. The prognostic ability of the SOAR and SOAR Na scores for mortality outcomes at both time points were then compared using the Area Under the Curve (AUC) values from the Receiver Operating Characteristic curves. RESULTS: A total of 8493 cases were included (male=47.4%, mean (SD) 77.7 (11.6) years). Compared with normonatremia (135-145 mmol/L), hypernatraemia (>145 mmol/L) was associated with inpatient mortality and moderate (125-129 mmol/L) and severe hypontraemia (<125 mmol/L) with 7-day mortality after adjustment for stroke type, Oxfordshire Community Stroke Project classification, age, prestroke modified Rankin score and sex. The SOAR and SOAR-Na scores both performed well in predicting inpatient mortality with AUC values of .794 (.78-.81) and .796 (.78-.81), respectively. 7-day mortality showed similar results. Both scores were less predictive in those with chronic kidney disease (CKD) and more so in those with hypoglycaemia. CONCLUSION: The SOAR-Na did not perform considerably better than the SOAR stroke score. However, the performance of SOAR-Na in those with CKD and dysglycaemias requires further investigation.

Age but not ABCD(2) score predicts any level of carotid stenosis in either symptomatic or asymptomatic side in transient ischaemic attack.

BACKGROUND: The ABCD(2) score is routinely used in assessment of transient ischaemic attack (TIA) to assess the risk of developing stroke. There remains uncertainty regarding whether the ABCD(2) score could be used to help predict extent of carotid artery stenosis (CAS). OBJECTIVES: We aimed to (i) collate and analyse all available published literature on this topic and (ii) compare the data from our local population to the existing evidence base. MATERIALS AND METHODS: We conducted a retrospective-observational study over a 6-month period using our East of England hospital-based TIA clinic data with a catchment population of ~750,000. We also searched the literature on studies reporting the association between ABCD(2) score and CAS. RESULTS: We included 341 patients in our observational study. The mean age in our cohort was 72.86 years (SD 10.91) with 52% male participants. ABCD(2) score was not significantly associated with CAS (p = 0.78). Only age > 60 years was significantly associated with ipsilateral (> 50%) and contralateral CAS (> 50% and > 70%) (p < 0.01) after controlling for other confounders. The systematic review identified four studies for inclusion and no significant association between ABCD(2) score and CAS was reported, confirming our findings. CONCLUSION: Our systematic review and observational study confirm that the ABCD(2) score does not predict CAS. However, our observational study has examined a larger number of possible predictors and demonstrates that age appears to be the single best predictor of CAS in patients presenting with a TIA. Selection of urgent carotid ultrasound scan thus should be based on individual patient's age and potential benefit of carotid intervention rather than ABCD(2) score.

The SOAR stroke score predicts hospital length of stay in acute stroke: an external validation study.

AIMS: The objective of this study is to externally validate the SOAR stroke score (Stroke subtype, Oxfordshire Community Stroke Project Classification, Age and prestroke modified Rankin score) in predicting hospital length of stay (LOS) following an admission for acute stroke. METHODS: We conducted a multi-centre observational study in eight National Health Service hospital trusts in the Anglia Stroke & Heart Clinical Network between September 2008 and April 2011. The usefulness of the SOAR stroke score in predicting hospital LOS in the acute settings was examined for all stroke and then stratified by discharge status (discharged alive or died during the admission). RESULTS: A total of 3596 patients (mean age 77 years) with first-ever or recurrent stroke (92% ischaemic) were included. Increasing LOS was observed with increasing SOAR stroke score (p < 0.001 for both mean and median) and the SOAR stroke score of 0 had the shortest mean LOS (12 ± 20 days) while the SOAR stroke score of 6 had the longest mean LOS (26 ± 28 days). Among patients who were discharged alive, increasing SOAR stroke score had a significantly higher mean and median LOS (p < 0.001 for both mean and median) and the LOS peaked among patients with score value of 6 [mean (SD) 35 ± 31 days, median (IQR) 23 (14-48) days]. For patients who died as in-patient, there was no significant difference in mean or median LOS with increasing SOAR stroke score (p = 0.68 and p = 0.79, respectively). CONCLUSION: This external validation study confirms the usefulness of the SOAR stroke score in predicting LOS in patients with acute stroke especially in those who are likely to survive to discharge. This provides a simple prognostic score useful for clinicians, patients and service providers.

Multi-frequency bioelectrical impedance analysis for assessing fat mass and fat-free mass in stroke or transient ischaemic attack patients.

BACKGROUND/OBJECTIVES: Dual energy X-ray absorptiometry (DEXA) is considered as the reference method in assessing fat-free and fat mass but is costly and not a pragmatic option in daily clinical practice. If devices based on multi-frequency bioelectrical impedance analysis (MF-BIA), which are cheaper and portable, are valid and reliable in measuring body composition, these could be used in routine clinical practice in nutritional management of patients and populations where malnutrition is prevalent. SUBJECTS/METHODS: A study of MF-BIA against DEXA in assessing fat-free and fat mass, and two internal validation studies of MF-BIA were conducted. Bland & Altman analysis to assess comparison against DEXA and Cronbach's α for internal validity were carried out. RESULTS: Ten participants (mean age 66 years; 70% men) with a recent stroke or transient ischaemic attack (TIA) were recruited to assess against DEXA and the first internal validation. The second internal validation was based on 80 pairs of MF-BIA measurements in 40 stroke patients (mean age 70.3 years; 55% men) assessed at hospital admission and on discharge. There was a strong correlation between MF-BIA and DEXA (correlation coefficient was 0.88 for fat-free mass and 0.77 for fat mass). According to Bland & Altman analysis, MF-BIA and DEXA fat-free and fat mass estimates were similar. Internal consistency was high with Cronbach's-α >0.9. CONCLUSION: MF-BIA can be reliably used in stroke and TIA patients. The feasibility, clinical and cost effectiveness of MF-BIA in routine monitoring and management of malnutrition in stroke and TIA patients with high prevalence of nutritional deficits is worthy of further evaluation.

TIA, stroke and orthostatic hypotension: a disease spectrum related to ageing vasculature?

AIMS: We sought to identify the determinants of orthostatic hypotension (OH) among patients referred to the transient ischaemic attack (TIA) clinic. METHODS: We conducted a retrospective analysis of prospectively collected data on patients who attended the TIA clinic in a UK hospital between January 2006 and September 2009. Each patient had their supine and standing or sitting blood pressure measured. Logistic regression was used to estimate the univariate and multivariate odds of OH for the subgroups of patients based on their diagnosis. A 10% significance level for the univariate analysis was used to identify variables in the multivariate model. RESULTS: A total of 3222 patients were studied of whom 1131 had a TIA, 665 a stroke and 1426 had other diagnoses. The prevalence of either systolic or diastolic OH in the TIA, stroke and patients with other diagnoses was similar being 22% (n = 251), 24% (n = 162) and 20% (n = 292), respectively. Multivariate analyses showed age, prior history of TIA, and diabetes were independently significantly associated with systolic OH alone or diastolic OH alone or either systolic or diastolic OH [ORs 1.03 (1.02-1.05); 1.56 (1.05-2.31); 1.65 (1.10-2.47), respectively]. Among the patients with the diagnosis of stroke, peripheral vascular disease (PVD) was significantly associated with increased odds of OH (3.56, 1.53-8.31), whereas male gender had a significantly lower odds of OH (0.61, 0.42-0.88). In patients with other diagnoses, age (1.04, 1.02-1.05) and diabetes (1.47, 1.04-2.09) were associated with OH, whereas male gender was (0.76, 0.58-1.00) not associated with OH. CONCLUSION: Orthostatic hypotension is prevalent among patients presenting to TIA clinic. Previous history of vascular disease (prior TIA/stroke/PVD) appears to be a significant associate of OH in this patient population.

Self-monitoring in hypertension: a web-based survey of primary care physicians.

Although self-monitoring of blood pressure is common among people with hypertension, little is known about how general practitioners (GPs) use such readings. This survey aimed to ascertain current views and practice on self-monitoring of UK primary care physicians. An internet-based survey of UK GPs was undertaken using a provider of internet services to UK doctors. The hyperlink to the survey was opened by 928 doctors, and 625 (67%) GPs completed the questionnaire. Of them, 557 (90%) reported having patients who self-monitor, 191 (34%) had a monitor that they lend to patients, 171 (31%) provided training in self-monitoring for their patients and 52 (9%) offered training to other GPs. Three hundred and sixty-seven GPs (66%) recommended at least two readings per day, and 416 (75%) recommended at least 4 days of monitoring at a time. One hundred and eighty (32%) adjusted self-monitored readings to take account of lower pressures in out-of-office settings, and 10/5 mm Hg was the most common adjustment factor used. Self-monitoring of blood pressure was widespread among the patients of responding GPs. Although the majority used appropriate schedules of measurement, some GPs suggested much more frequent home measurements than usual. Further, interpretation of home blood pressure was suboptimal, with only a minority recognising that values for diagnosis and on-treatment target are lower than those for clinic measurement. Subsequent national guidance may improve this situation but will require adequate implementation.

A systematic review of the pharmacological management of orthostatic hypotension.

OBJECTIVES: The 'short' and 'long-term' benefits of pharmacological interventions to treat orthostatic hypotension (OH) remain unclear. The aim was to systematically examine the published literature on the effectiveness of different drug regimens for the treatment of OH. DESIGN: Systematic review. SETTING: MEDLINE (1950-Week 7, 2011), EMBASE (1980-Week 7, 2011), CINAHL (1981-Week 7, 2011) databases and hand-searching of bibliographies were used to identify suitable papers. PARTICIPANTS: Studies selected were those, which investigated drug treatment of OH in a single- or double-blind randomised controlled trial (RCT) in humans over 18 years of age. MEASUREMENTS: Data were extracted from suitable full-text articles by three investigators independently. RESULTS: The 13 trials met the criteria for systematic review amongst which was considerable variation in the size of postural blood pressure (BP) change with active treatment. However, there was evidence that commonly used drugs midodrine or fludrocortisone therapy did increase standing or head-up-tilt (HUT) systolic blood pressure in certain patient groups. CONCLUSION: The evidence that pharmacological therapy is of benefit for the treatment of OH is limited by the lack of good quality clinical trial evidence. Further well-designed RCTs of pharmacological treatment of OH investigating the impact on postural symptoms as well as actual BP changes are needed.

Predictors of early mortality among hospitalized nursing home residents.

BACKGROUND: Emergency admissions from nursing homes (NHs) are associated with high mortality. Understanding the predictors of early mortality in these patients may guide clinicians in choosing appropriate site and level of care. METHODS: We identified all consecutive admissions from NHs (all ages) to an Acute Medical Assessment Unit between January 2005 and December 2007. Analysis was performed at the level of the admission. The predictors of in-patient mortality at 7 days were examined using a generalized estimating equations analysis. RESULTS: A total of 314 patients [32% male, mean age: 84.2 years (SD: 8.3 years)] were admitted during the study period constituting 410 emergency episodes. Twenty-three percent of admissions resulted in hospital mortality with 73% of deaths occurring within 1 week (50% within the first 3 days). For 7-day mortality outcome, patients with a modified early warning score (MEWS) of 4-5 on admission had 12 times the odds of death [95% confidence interval (CI) 1.40-103.56], whereas those with a score of ≥6 had 21 times the odds of death (95% CI 2.71-170.57) compared with those with a score of ≤1. An estimated glomerular filtration rate (eGFR) of 30-60 and <30 ml/min/m(2) was associated with nearly a 3-fold increase in the odds of death at 1 week (95% CI 1.10-7.97) and a 5-fold increase in the odds of death within 1 week (95% CI 1.75-14.96), respectively, compared with eGFR > 60 ml/min/m(2). C-reactive protein (CRP) >100 mg/l on admission was also associated with a 2.5 times higher odds of death (95% CI 1.23-4.95). Taking eight or more different medication items per day was associated with only a third of the odds of death (95% CI 0.09-0.98) compared with patients taking only three or fewer per day. CONCLUSION: In acutely ill NH residents, MEWS is an important predictor of early hospital mortality and can be used in both the community and the hospital settings to identify patients whose death maybe predictable or unavoidable, thus allowing a more holistic approach to management with discussion with patient and relatives for planning of immediate care. In addition, CRP and eGFR levels on admission have also been shown to predict early hospital mortality in these patients and can be used in conjunction with MEWS in the same way to allow decision making on the appropriate level of care at the point of hospital admission.

Current practice of carotid endarterectomy in the UK.

BACKGROUND: Carotid endarterectomy (CEA) reduces the risk of stroke in patients with internal carotid stenosis of 50-99 per cent. This study assessed national surgical practice through audit of CEA procedures and outcomes. METHODS: This was a prospective cohort study of UK surgeons performing CEA, using clinical audit data collected continuously and reported in two rounds, covering operations from December 2005 to December 2007, and January 2008 to September 2009. RESULTS: Some 352 (92·6 per cent) of 380 eligible surgeons contributed data. Of 19,935 CEAs recorded by Hospital Episode Statistics, 12,496 (62·7 per cent) were submitted to the audit. A total of 10,452 operations (83·6 per cent) were performed for symptomatic carotid stenosis; among these patients, the presenting symptoms were transient ischaemic attack in 4507 (43·1 per cent), stroke in 3572 (34·2 per cent) and amaurosis fugax in 1965 (18·8 per cent). The 30-day mortality rate was 1·0 per cent (48 of 4944) in round 1 and 0·8 per cent (50 of 6151) in round 2; the most common cause of death was stroke, followed by myocardial infarction. The rate of death or stroke within 30 days of surgery was 2·5 per cent (124 of 4918) in round 1 and 1·8 per cent (112 of 6135) in round 2. CONCLUSION: CEA is performed less commonly in the UK than in other European countries and probably remains underutilized in the prevention of stroke. Increasing the number of CEAs done in the UK, together with reducing surgical waiting times, could prevent more strokes.

Atrial fibrillation and incidence of dementia: a systematic review and meta-analysis.

BACKGROUND: Previous systematic reviews that examined whether atrial fibrillation (AF) is associated with dementia have relied on different study designs (including retrospective ones) and did not evaluate risk using meta-analysis. METHODS: We searched Medline, Embase, and PsychINFO in September 2010 for published prospective studies reporting on the association between baseline AF and incident dementia. Pooled odds ratios for AF and dementia were calculated using the random effects model, with heterogeneity assessed using I(2). RESULTS: We identified 15 relevant studies covering 46,637 participants, mean age 71.7 years. One study that reported no significant difference in Mini-Mental State Examination scores between patients with or without AF could not be pooled. Meta-analysis of the remaining 14 studies showed that AF was associated with a significant increase in dementia overall (odds ratio [OR] 2.0, 95% confidence interval [CI] 1.4 to 2.7, p < 0.0001), with substantial heterogeneity (I(2) = 75%). When stratified by participants, the association was significant (with little heterogeneity) in studies focusing solely on patients with stroke (7 studies, OR 2.4, 95% CI 1.7 to 3.5, p < 0.001, I(2) = 10%), and of borderline significance (with substantial heterogeneity) for studies in broader populations (7 studies, OR 1.6, 95% CI 1.0 to 2.7, p = 0.05, I(2) = 87%). For conversion of mild cognitive impairment to dementia, one study showed a significant association with AF (OR 4.6, 95% CI 1.7 to 12.5). CONCLUSION: There is consistent evidence supporting an association between AF and increased incidence of dementia in patients with stroke whereas there remains considerable uncertainty about any link in the broader population. The potential association between AF and incident dementia in mild cognitive impairment merits further investigation.

Age, co-morbidity and poor mobility: no evidence of predicting in-patient death and acute hospital length of stay in the oldest old.

BACKGROUND: The oldest old (aged over 90 years) are the fastest growing section of the UK population. Limited data exist regarding the effect of age, location, co-morbidity and physical performance status on outcome of acute illness in this age group. METHODS: We performed a prospective study in people aged ≥ 90 years using hospital audit data in three hospitals in England and Scotland. We examined the characteristics of those admitted over three consecutive calendar months and calculated risk ratios of death and prolonged length of acute hospital stay (>7 days). RESULTS: A total of 419 patients were included in this study (68% female, median age 93 years). There were similarities in presentation and diagnoses, but patients in Scotland (n = 164) were more likely to be admitted from sheltered housing or nursing homes than those in England (n = 255). Patients in England were significantly less likely to be able to mobilize < 10 m (41 vs. 34%, P < 0.001) but had lower prevalence of hypertension (40 vs. 55%, P = 0.02), ischaemic heart disease (30% vs. 45%, P = 0.02) and fewer prescribed medications (median 2 vs. 3, P < 0.001). Mortality was similar for the England and Scotland centres (P = 0.98). Previously recognized risk factors for death following hospital admission and length of stay e.g. older age, higher number of co-morbidities and poor mobility were not predictive in this study. CONCLUSION: The 'oldest old' should not be considered as a homogenous group and findings from single-centre studies involving this age group may not be generalizable. We found no conclusive evidence that patient-related factors predict outcome in this age group in acute medical admission settings.

High mortality of older patients admitted to hospital from care homes and insight into potential interventions to reduce hospital admissions from care homes: the Norfolk experience.

There is a high mortality rate in patients admitted to hospitals acutely from care homes. In a retrospective case analysis study of 3772 older people admitted to the Department of Medicine for the Elderly between January and June 2005, 340 (9.0%) were from care homes, and 93 (27.3%) of the residents died during the index admission. Nearly 40% of these deaths occurred within 24h of admission indicating a high level of less appropriate admissions. Investigating eight nursing homes which admitted the highest number of patients from one primary care trust revealed that the most cited reasons for admission were the lack of advance care plans, access to General Practitioners (GPs) out of hours, as well as general access to palliative care and specialist nurses, and poor communication between patient, relatives, GPs, hospitals and care home staff. Our findings provide some useful insight into the factors that need to be addressed to avoid unnecessary or inappropriate admissions from care homes for better end of life care in aging societies.

Death-associated protein kinase (DAPK1) in cerebral cortex of late-onset Alzheimer's disease patients and aged controls.

AIMS: Here our objective was to detect the pro-apoptotic serine/threonine kinase death-associated protein kinase (DAPK1) in aged human cerebral cortex and to test the hypothesis that DAPK1 abundance is associated with late-onset Alzheimer's disease (AD). METHODS: Using Western analysis and immunohistochemistry we evaluated post mortem frontal cerebral cortex from patients with severe AD (mean age 76 years, range 66-91, n = 11, all male), and from control cases without serious central nervous system illness (mean age 77 years, range 61-95, n = 12, all male). We also examined brains of Tg2576 transgenic mice (males, aged 16-21 months), a model for chronic amyloid-induced brain injury. RESULTS: Immunohistochemical labelling showed DAPK1 expression in cortical neurones of human cortex and axonal tracts within subcortical white matter, both in AD and in control brains. Western analysis confirmed DAPK1 expression in all samples, although expression was very low in some control cases. DAPK1 abundance in the AD group was not significantly different from that in controls (P = 0.07, Mann-Whitney test). In brains of Tg2576 mice DAPK1 abundance was very similar to that in wild-type littermates (P = 0.96, Mann-Whitney test). CONCLUSION: We found that DAPK1 was expressed in neurones of aged human frontal cortex, both in AD and in control cases.

Continuous estimates of dynamic cerebral autoregulation: influence of non-invasive arterial blood pressure measurements.

Temporal variability of parameters which describe dynamic cerebral autoregulation (CA), usually quantified by the short-term relationship between arterial blood pressure (BP) and cerebral blood flow velocity (CBFV), could result from continuous adjustments in physiological regulatory mechanisms or could be the result of artefacts in methods of measurement, such as the use of non-invasive measurements of BP in the finger. In 27 subjects (61+/-11 years old) undergoing coronary artery angioplasty, BP was continuously recorded at rest with the Finapres device and in the ascending aorta (Millar catheter, BP(AO)), together with bilateral transcranial Doppler ultrasound in the middle cerebral artery, surface ECG and transcutaneous CO(2). Dynamic CA was expressed by the autoregulation index (ARI), ranging from 0 (absence of CA) to 9 (best CA). Time-varying, continuous estimates of ARI (ARI(t)) were obtained with an autoregressive moving-average (ARMA) model applied to a 60 s sliding data window. No significant differences were observed in the accuracy and precision of ARI(t) between estimates derived from the Finapres and BP(AO). Highly significant correlations were obtained between ARI(t) estimates from the right and left middle cerebral artery (MCA) (Finapres r=0.60+/-0.20; BP(AO) r=0.56+/-0.22) and also between the ARI(t) estimates from the Finapres and BP(AO) (right MCA r=0.70+/-0.22; left MCA r=0.74+/-0.22). Surrogate data showed that ARI(t) was highly sensitive to the presence of noise in the CBFV signal, with both the bias and dispersion of estimates increasing for lower values of ARI(t). This effect could explain the sudden drops of ARI(t) to zero as reported previously. Simulated sudden changes in ARI(t) can be detected by the Finapres, but the bias and variability of estimates also increase for lower values of ARI. In summary, the Finapres does not distort time-varying estimates of dynamic CA obtained with a sliding window combined with an ARMA model, but further research is needed to confirm these findings in healthy subjects and to assess the influence of different physiological manoeuvres.

Drenching adult ewes: implications of anthelmintic treatments pre- and post-lambing on the development of anthelmintic resistance.

AIMS: To test the hypothesis that peri-parturient anthelmintic treatment of adult ewes, either pre-lambing with a controlled- release capsule (CRC) or at tail-docking with a short-acting oral formulation, would increase the rate of development of anthelmintic resistance, as compared to not drenching ewes and giving an additional drench to lambs in the autumn. Also, to evaluate the potential of routinely leaving 15% of the heaviest lambs untreated when drenching, as a means of slowing the development of anthelmintic resistance. METHODS: A replicated farmlet trial was run from 1999- 2004. Eleven farmlets, each consisting of five paddocks, were initially seeded with Ostertagia (=Teladorsagia) circumcincta and Trichostrongylus colubriformis parasites, these being a mixture of albendazole-susceptible and -resistant isolates to yield a 96% reduction in faecal nematode egg count (FEC) on drenching. Four prescriptive drenching regimes were applied; Treatments 1-3 were replicated three times and Treatment 4 twice. Treatments were as follows. Treatment 1: Ewes were given an albendazole CRC pre-lambing, and any ewes exceeding 65 kg liveweight were given two capsules simultaneously; lambs were given a five-drench preventive programme of treatments, orally, of albendazole on Days 0, 21, 42, 70 and 98 after weaning. Treatment 2: Ewes were given a single oral treatment of albendazole at docking (2-3 weeks after lambing), and lambs were given the same five-drench preventive programme as in Treatment 1. Treatment 3: Ewes remained untreated, while lambs were given a six-drench preventive programme of treatments, orally, of albendazole on Days 0, 21, 42, 70, 98 and 126 after weaning. Treatment 4: Ewes remained untreated, while lambs were given the same six-drench preventive programme as in Treatment 3, but the heaviest 15% of lambs were left untreated each time. Albendazole-resistance status was measured at least twice-yearly, using faecal egg count reduction tests (FECRTs) and larval development assays (LDA). In addition, controlled slaughter of drenched and undrenched tracer lambs was undertaken in the last 3 years. RESULTS: Resistance to albendazole increased most rapidly in Treatment 1, as measured by FECRT and LDA results, and worm burdens in tracer lambs. In Treatment 2, resistance developed slower than in Treatment 1 but faster than in Treatments 3 and 4, as measured by LDA; resistance in Treatment 2 developed more quickly than in Treatment 4, as measured by FECRTs. There was no significant difference between Treatments 3 and 4, although this approached significance in Ostertagia spp, as measured by LDA. CONCLUSIONS: Anthelmintic treatments to adult ewes around lambing time are likely to be more selective for resistance than additional treatments administered to lambs in the autumn. Farmers wishing to slow the emergence of anthelmintic resistance on their farms should look to minimise the administration of peri-parturient treatment of ewes. A trend to slower development of resistance where a proportion of lambs were left untreated at each drench suggests further work on this aspect of management of resistance is warranted.

Cerebral critical closing pressure estimation from Finapres and arterial blood pressure measurements in the aorta.

Estimates of cerebral critical closing pressure (CrCP) and resistance-area product (RAP) are often derived using noninvasive measurements of arterial blood pressure (ABP) in the finger, but the errors introduced by this approach, in relation to intra-vascular measurements of ABP, are not known. Continuous recordings of ABP (Finapres and solid-state catheter-tip transducer in the ascending aorta), cerebral blood flow velocity (CBFV, bilateral Doppler), ECG and transcutaneous CO(2) were performed following coronary catheterization. CrCP and RAP were calculated for each of 12,784 cardiac cycles from 27 subjects using the classical linear regression (LR) of the instantaneous CBFV-ABP relationship and also the first harmonic (H(1)) of the Fourier transform. There was a better agreement between LR and H(1) for the aortic measurements than for the Finapres (p < 0.000,01). For LR there were no significant differences for either CrCP or RAP due to the source of ABP measurement, but for H(1) the differences were highly significant (p < 0.000,03). The coherence functions between either CrCP or RAP values calculated with aortic pressure (input) or the Finapres (output) were significantly higher for H(1) than for LR for most harmonics below 0.2 Hz. When using the Finapres to estimate CrCP and RAP values, the LR method produces similar results to intra-arterial measurements of ABP for time-averaged values, but H(1) should be preferred in applications analysing beat-to-beat changes in these parameters.

A study of statin use in the prevention of cognitive impairment of vascular origin in the UK.

INTRODUCTION: There is increasing evidence suggesting that control of hypertension and antiplatelet therapy may prevent or reduce progression of vascular-related cognitive impairment (VCI), though a similar role of statins in this group of patients has yet to be established. METHODS: We conducted a postal survey of a group of 296 medical practitioners (comprising of physicians and psychiatrists specialising in the elderly, and general practitioners) inquiring into their management of (a) patients at high risk of developing VCI and (b) patients with established VCI. RESULTS: The overall response rate was 60% (177/296), with the highest response rate from psychiatrists. (a) For patients at high risk of developing VCI: 47% of clinicians believed that statins had an important role in preventing subsequent dementia: 4% would commence statins at a total cholesterol (TC) of 4-5 mmol/L; 38% with a TC of 5.1-6.5 mmol/L; and 32% with a TC of 6.6-8 mmol/L. Cardiovascular risk profile, age, cost and gender were other factors considered as important factors influencing statin prescription. (b) In those patients with established VCI: 32% of clinicians felt that statins had an important role in arresting progression, usually in people with a mild degree of cognitive impairment: 4% would commence statins at a TC of 4-5 mmol/L; 25% with a TC of 5.1-6.5 mmol/L; and 22% with a TC of 6.6-8 mmol/L. There were no major differences between clinicians in their prescribing habits. CONCLUSIONS: A substantial proportion of clinicians favour the use of statins in primary and secondary prevention of cognitive impairment of vascular origin, despite a lack of definite evidence to support their use at the present time.