The cost of cerebral ischaemia.

Cerebral ischaemia is a major cause of disability and death globally and has a profoundly negative impact on the individuals it affects, those that care for them and society as a whole. The most common and familiar manifestation is stroke, 85% of which are ischaemic and which is the second leading cause of death and most common cause of complex chronic disability worldwide. Stroke survivors often suffer from long-term neurological disabilities significantly reducing their ability to integrate effectively in society with all the financial and social consequences that this implies. These difficulties cascade to their next of kin who often become caregivers and are thus indirectly burdened. A more insidious consequence of cerebral ischaemia is progressive cognitive impairment causing dementia which although less abrupt is also associated with a significant long-term disability. Globally cerebrovascular diseases are responsible for 5.4 million deaths every year (1 in 10 of total). Approximately 3% of total healthcare expenditure is attributable to cerebral ischaemia with cerebrovascular diseases costing EU healthcare systems 21 billion euro in 2003. The cost to the wider economy (including informal care and lost productivity) is even greater with stroke costing the UK 7-8 billion pound in 2005 and the US $62.7 billion in 2007. Cerebrovascular disease cost the EU 34 billion euro in 2003. From 2005 to 2050 the anticipated cost of stroke to the US economy is estimated at $2.2 trillion. Given the global scale of the problem and the enormous associated costs it is clear that there is an urgent need for advances in the prevention of cerebral ischaemia and its consequences. Such developments would result in profound benefits for both individuals and their wider societies and address one of the world's most pre-eminent public health issues.

Secondary prevention of stroke.

Stroke is a common disorder and a leading cause of disability and death. Ischaemia is a more common cause than haemorrhage and radiological imaging is required to accurately differentiate these. Some specific risk factors for stroke are non-modifiable--these include age, gender, racial and hereditary factors. Certain risk factors for ischaemic stroke can be identified and modification of these can be used for secondary prevention--examples include hypertension, heart diseases, atrial fibrillation, diabetes mellitus, dyslipidaemia, smoking, excessive alcohol consumption and carotid stenosis. Carotid endarterectomy is valuable in selected patients. In ischaemic stroke and transient ischaemic attack antithrombotic therapy is an option used in secondary prevention. In atrial fibrillation, warfarin should be used where possible in secondary prevention. When warfarin is contraindicated aspirin should be used. In other patients, an antiplatelet regime is appropriate--aspirin is commonly used and is the least expensive regime. Other antiplatelet agents such as dipyridamole, ticlopidine and clopidogrel may have a place. Younger patients with ischaemic stroke may have a thrombophilia state and should be appropriately investigated.

Biologic variation of common hematologic laboratory quantities in the elderly.

Analytic, within-subject, and between-subject biologic variations were estimated for leukocytes, erythrocytes, hemoglobin, hematocrit, mean cell volume (MCV), mean cell hemoglobin (MCH), mean cell hemoglobin content (MCHC), platelets, and a three-component differential count (lymphocytes, monocytes, and granulocytes in terms of both concentration and percentage of leukocytes) in cohorts of 12 male and 12 female healthy elderly subjects. The assays were performed with an Ortho ELT-800 automated analyzer. The estimates of within-subject biologic variation were similar to published data on young subjects, indicating that this aspect of homeostasis is not compromised in the elderly. The data were used to derive objective analytic goals; goals were surpassed except for assays of erythrocytes, hematocrit, and the derived MCV, MCH, and MCHC. The changes required for serial results to be significantly different were determined and found to be generally valid because most quantities have no heterogeneity of within-subject variation. All quantities had significant individuality; in consequence, conventional population-based reference values are of limited utility, and screening using reference limits will not detect latent or early disease in many subjects.

Cluster-randomized, controlled trial of computer-based decision support for selecting long-term anti-thrombotic therapy after acute ischaemic stroke.

BACKGROUND: Identifying the appropriate long-term anti-thrombotic therapy following acute ischaemic stroke is a challenging area in which computer-based decision support may provide assistance. AIM: To evaluate the influence on prescribing practice of a computer-based decision support system (CDSS) that provided patient-specific estimates of the expected ischaemic and haemorrhagic vascular event rates under each potential anti-thrombotic therapy. DESIGN: Cluster-randomized controlled trial. METHODS: We recruited patients who presented for a first investigation of ischaemic stroke or TIA symptoms, excluding those with a poor prognosis or major contraindication to anticoagulation. After observation of routine prescribing practice (6 months) in each hospital, centres were randomized for 6 months to either control (routine practice observed) or intervention (practice observed while the CDSS provided patient-specific information). We compared, between control and intervention centres, the risk reduction (estimated by the CDSS) in ischaemic and haemorrhagic vascular events achieved by long-term anti-thrombotic therapy, and the proportions of subjects prescribed the optimal therapy identified by the CDSS. RESULTS: Sixteen hospitals recruited 1952 subjects. When the CDSS provided information, the mean relative risk reduction attained by prescribing increased by 2.7 percentage units (95%CI -0.3 to 5.7) and the odds ratio for the optimal therapy being prescribed was 1.32 (0.83 to 1.80). Some 55% (5/9) of clinicians believed the CDSS had influenced their prescribing. CONCLUSIONS: Cluster-randomized trials provide excellent frameworks for evaluating novel clinical management methods. Our CDSS was feasible to implement and acceptable to clinicians, but did not substantially influence prescribing practice for anti-thrombotic drugs after acute ischaemic stroke.

Reversible hypertension following coeliac disease treatment: the role of moderate hyperhomocysteinaemia and vascular endothelial dysfunction.

The vascular endothelium maintains a relatively vasodilated state via the release of nitric oxide (NO), a process that could be disrupted by hyperhomocysteinaemia. Since endothelial dysfunction is associated with increased systemic vascular resistance that is the hallmark of sustained arterial hypertension, we hypothesised that in patients with both hypertension and coeliac disease with hyperhomocysteinaemia (via malabsorption of essential cofactors), treatment of the latter disease could improve blood pressure (BP) control. A single patient with proven sustained hypertension and newly-diagnosed coeliac disease had baseline and post-treatment BP and endothelial function assessed by ambulatory BP monitoring (ABPM) and brachial artery forearm occlusion plethysmography respectively. This 49 year-old woman had uncomplicated sustained hypertension proven on repeated ABPM carried out 6 weeks apart (daytime mean 151/92 mm Hg and 155/95 mm Hg), and sub-clinical coeliac disease (gluten-sensitive enteropathy). Initial assessments revealed raised homocysteine levels with low normal vitamin B(12) level. It was likely that she had impaired absorption of essential cofactors for normal homocysteine metabolism. She adhered to a gluten-free diet and was give oral iron, folate and B(6) supplementations as well as B(12) injections for 3 months. Her BP had improved by 6 months and normalised by 15 months (daytime ABPM mean 128/80 mm Hg). There was parallel restoration of normal endothelial function with normalisation of her homocysteine levels. These observations suggest that sub-clinical coeliac disease related hyperhomocysteinaemia might cause endothelial dysfunction, potentially giving rise to a reversible form of hypertension. In addition, this case study supports the notion that irrespective of aetiology, endothelial dysfunction may be the precursor of hypertension. This highlights the need to resolve co-existing vascular risk factors in patients with hypertension.

Does a prolonged QT peak identify left ventricular hypertrophy in hypertension?

BACKGROUND: Left ventricular hypertrophy is a powerful predictor of death. Hypertensive subjects with left ventricular hypertrophy can have increased QT (end) dispersion, which is associated with cardiac death. Despite its prognostic value, QT (end) dispersion is not widely used. QTp (i.e. start of QRS to peak of T wave) is easier to measure. Therefore, we tested the hypothesis that long QT peak was associated with left ventricular hypertrophy and assessed its cost-effectiveness at diagnosing left ventricular hypertrophy. METHODS: ECGs and echocardiograms were recorded in 47 hypertensive patients. The onset of the QRS complex and peak of T wave of lead I of each subject's ECGs were digitised by one observer blind to results of the echocardiogram. Receiver-operator characteristics curves were plotted to determine the sensitivity and specificity of different cut-off values of QT peak at predicting left ventricular hypertrophy (defined as left ventricular mass index> or =134 g/m2 in male, > or =110 g/m2 in female). RESULTS: The heart-rate corrected QT peak of lead I correlated with left ventricular mass index (r=0.45, P=0.002). If all patients with a prolonged QT peak (> or =300 ms) had an echocardiogram, then no cases of left ventricular hypertrophy would be missed (100% sensitive). This novel ECG criterion not only had better positive and negative predictive values than the Sokolow-Lyon voltage criteria, but also resulted in more cost-effective resource use (< pound 370 vs. pound 1750/case of left ventricular hypertrophy detected). CONCLUSION: If the results of this small pilot study are confirmed in larger studies, then measuring QT peak of lead I may become a cost-effective way of identifying hypertensives who are likely to have echocardiographic left ventricular hypertrophy.

Which acute stroke patients with atrial fibrillation are prescribed warfarin therapy? Results from one-year's experience in Dundee.

The recommended treatment of ischaemic stroke patients with atrial fibrillation (AF) is anticoagulation therapy with warfarin sodium and if this is contraindicated then aspirin should be used. The management of patients on warfarin therapy can be complicated and there is a risk of intra-cranial haemorrhage in elderly patients. However, these are the patients who stand to gain the most benefit from this treatment and therefore increased use of warfarin for secondary prophylaxis is likely to lead to a lower rate of subsequent admissions and less morbidity. The recommended treatment for these patients has often not been fully instigated in practice. This study was carried out in order to determine whether a group of patients admitted to a teaching hospital with diagnosis of ischaemic stroke and atrial fibrillation received appropriate antithrombotic therapy. Details of patients admitted with acute stroke during 1997 were obtained from the Dundee Stroke Database and information was extracted from the relevant clinical notes. Twenty-five out of 42 patients (60%) were considered eligible for anticoagulation and 14 out of those 25 (56%) were found to be on warfarin either on admission or subsequently. Of patients aged less than 75 years, 8/10 (80%) were on warfarin, whereas only 6/15 (40%) of those aged 75 years and older were being anticoagulated.

The management of acute headache in adults in an acute admissions unit.

There have been no previously published studies about acute admissions with headaches to a medical admissions ward. In our retrospective case-note study of all patients admitted with headaches to the acute medical admission ward of Ninewells Hospital, Dundee over a six-month period, there were 114 admissions with headache (2.4% of all admissions). CT scans were done in 68 (59.6%) and were abnormal in 21 patients. Twenty four patients (21.1%) had serious underlying causes for headaches. Predictors for CT abnormalities are discussed. Eighteen patients had lumbar punctures and six had abnormal results. Most patients were discharged after one day, nine were transferred to the neurosurgical unit and there were two deaths. Deficiencies in record keeping were identified as was a lack of precision in diagnosis. Changes in practice are needed to improve patient care and perhaps national guidelines are required.

The importance of identifying intracranial haemorrhage as a cause of transient focal neurological symptoms.

Until recently, there have been no reports of intracerebral haemorrhage presenting with transient neurological symptoms. We present two cases of intracerebral haemorrhage presenting as transient ischaemic attacks and discuss the radiological changes on early and late CT scans. It would seem justified to scan most patients presenting with TIA early to institute appropriate secondary prevention measures.

Relationship of volume of lesion to length of hospital stay and outcome at one year in stroke patients.

The aim of this study was to investigate the relationship between the volume of lesion (VOL) in patients with stroke and the associated length of hospital stay (LOS), as well as longer-term functional outcome. Computerised tomography (CT) scans were used to measure the volume, region and type of lesion, volume being measured by planimetry. LOS and other patient details were obtained from the Dundee Stroke Database. The total LOS was associated with the VOL on univariate analysis (p = 0.004) and after adjustment for the other variables (p = 0.006) due to a larger lesion being associated with longer stay in hospital. Patient follow-up confirmed that the VOL was also highly significant when related to functional outcome measures of impairment, disability and handicap at one year, as determined by Orgogozo (p = 0.03), Barthel (p < 0.01) and Rankin scores (p < 0.01) respectively. The VOL is related to the length of stay in hospital and outcome at one year. This is of particular interest with the increasing use of thrombolysis and development of neuroprotectant agents designed to limit VOL.

Mortality during the winter flu epidemic--two cases of death associated with self-medication.

We report two cases of mortality associated with the recent winter influenza outbreak. Both cases were associated with self-medication. In one case an elderly lady died from haemorrhagic duodenitis induced by over the counter ibuprofen. In the second case the lady died from the consequences of exceeding the recommended doses of paracetamol by combining doses of the generic product with proprietary flu-remedies and Tylex (paracetamol and codeine).

The differential diagnosis of polycythaemia--a bone marrow study (the bone marrow in polycythaemia).

Bone marrow sections from posterior iliac crest aspiration and/or trephine specimens have been examined in 39 patients with true polycythaemia, along with a variety of other clinical and laboratory data. The emphasis has been on objective assessment of cellularity and megakaryocyte concentration in a prospective four year study. In patients with untreated primary polycythaemia mean cellularity was 87.0% and 86.4% for aspirate and trephine specimens compared with 55.5% and 48.7% for secondary cases and 48.3% and 45.5% for controls. Eighty per cent of primary polycythemia patients had moderate to marked megakaryocytic hyperplasia. We conclude that, in the presence of an elevated red cell volume, marrow cellularity of greater than 75%, particularly when accompanied by megakaryocytic hyperplasia, of iliac crest aspirate or trephine specimens is sufficient per se to establish a diagnosis of polycythaemia rubra vera.

Cyclical etidronate and calcium carbonate (with citrate) supplementation for osteoporosis unmasking primary hyperparathyroidism.

An 88 year old lady undergoing cyclical etidronate and calcium carbonate (with citrate) therapy for vertebral osteoporosis was found to be symptomatically hypercalcaemic at the end of the first cycle of treatment. She had been previously asymptomatic and normocalcaemic, but was subsequently found to have primary hyperparathyroidism. This condition is most prevalent in postmenopausal females--the same patient group at risk of osteoporosis. Serum calcium should be measured after commencing cyclical etidronate and calcium carbonate. If hypercalcaemia is detected primary hyperparathyroidism should be excluded as an underlying, cause.

Subacute gastric volvulus--a rare cause of vomiting in the elderly.

We report a case of an important and uncommon cause of vomiting in an elderly female patient who had no previous apparent gastrointestinal problems. A diaphragmatic hernia with gastric volvulus, which presented non-specifically but was an important diagnosis to make.

The Dundee Stroke Register: experience of the first ten years.

The objective to establish a register of all patients admitted to Dundee hospitals with acute stroke has been achieved. To do this a computerised database system has been established and a prospective survey has been conducted of clinical data of patients at time of admission, with follow-up at one and three years. All patients with a WHO diagnosis of acute stroke (excluding patients with subarachnoid haemorrhage), from January 1988 have been recorded. By the end of 1998, 3222 patients had been registered. The Dundee Stroke register database is the largest in Scotland and one of the largest in the world. The establishment of the register and database has required substantial investment of resources and the collaboration of the NHS, universities and the private sector. The operation of the register has heightened interest in stroke. It also provides present and future opportunities for clinical research and audit studies and the monitoring of outcomes.

Empyema of lung associated with Streptococcus milleri infection.

Empyema of the lung is a very serious illness which must be detected quickly and treated aggressively. We report an unusual case of empyema of the lung associated with a boating accident while the patient was fishing in a sea loch off the west coast of Scotland.

Myocardial fibrosis and QTc are reduced following treatment with spironolactone or amiloride in stroke survivors: a randomised placebo-controlled cross-over trial.

INTRODUCTION: Myocardial fibrosis is dysrhythmogenic and may contribute to the high incidence of cardiac death in stroke survivors, especially if they have long QTc. We tested the hypothesis that procollagen-1-carboxy terminal peptide (P1CP), a biomarker of myocardial fibrosis, might be improved following treatment with spironolactone or amiloride in stroke survivors. We also tested the hypothesis that both drugs would shorten QTc. STUDY DESIGN: randomised, double-blinded, placebo-controlled, cross-over trial (spironolactone vs. amiloride vs. placebo). Duration of Study: 3 months (1 month per drug). Primary endpoints: P1CP, QTc RESULTS: 11 stroke survivors (5 female), aged 71 ± 4, BP 139/81 mmHg ± 20/11 mmHg, completed the study. Both spironolactone and amiloride significantly reduced P1CP [Spironolactone-Placebo = -24 ug/L, 95% CI = -40 to -6.9; Amiloride-Placebo = -28 ug/L, 95% CI = -44 to -11]. Spironolactone and amiloride both shortened QTc [Spironolactone vs. Placebo=-18 ms(1/2), 95% CI = -36 to -0.55; Amiloride vs Placebo = -25 ms(1/2), 95% CI = -42 to -7.5]. CONCLUSIONS: Procollagen-1-carboxy terminal peptide was reduced following treatment with spironolactone within a month. Further, this is the first study demonstrating amiloride could also improve myocardial fibrosis. The beneficial effects of both drugs on myocardial fibrosis, coupled with their effects on raising potassium translated to a shortening of QTc. Future studies should test the hypothesis that these drugs might reduce the risk of sudden cardiac death in stroke survivors.