Current status of screening for diabetic retinopathy in the UK.
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Diabetic Retinopathy↗
Biomedical subjects
J Slattery
Publications and source records attributed to J Slattery.
Placebo surgery in trials of therapy for Parkinson's disease.
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Ethics, Medical↗
Phase I topotecan preparative regimen for high-risk neuroblastoma, high-grade glioma, and refractory/recurrent pediatric solid tumors.
We evaluated the toxicity and maximum tolerated dose of topotecan in a novel myeloablative regimen as treatment for high-risk pediatric tumors. Patients received an assigned topotecan dosage in combination with fixed doses of carboplatin and thiotepa, followed by autologous hematopoietic stem cells infusion. Topotecan dose was escalated in cohorts of four patients until the maximum tolerated dose of topotecan was defined or until accrual of 30 patients. Pharmacokinetics of topotecan were examined, and event-free survival was estimated. We describe preliminary results following treatment of 25 pediatric patients with high-risk solid tumors.
Antineoplastic Agents↗
Identification of neonates at risk of developing feeding problems in infancy.
The increased survival of sick and preterm neonates may be associated with long-term problems which must be recognised and managed if outcome is to be optimised. In a prospective study of 35 neonates (median gestational age at birth 34 weeks) admitted to a neonatal intensive care unit over a 3-month period, we have documented a high incidence (14 of 35) of immature or abnormal feeding patterns when infants were assessed at 36 to 40 weeks postmenstrual age. Neonates with prolonged respiratory support and delayed enteral and oral feeding were most affected. Compared with neonates who have normal initial feeding assessments, neonates with disorganised or dysfunctional feeding were six times more likely to vomit and three times more likely to cough when offered solid food at 6 months of age. At 12 months of age significant differences were also found in tolerating lumpy food and enjoying mealtimes. We hypothesise that these feeding problems contribute to failure to thrive and psychosocial distress after discharge from the neonatal unit and propose potential neonatal measures to reduce their incidence.
Enteral Nutrition↗
Use of a neonatal blood pressure cuff to monitor blood pressure in the adult finger--comparison with a standard adult arm cuff.
BACKGROUND: There are few suitable methods for monitoring blood pressure continuously (or intermittently) for research in adult stroke patients, who are ill but do not justify invasive intensive care monitoring. METHOD: We tested a neonatal arm blood pressure in adults by placing it on the forefinger ("finger cuff"). We compared the repeatability of the finger cuff with blood pressure measured by a standard adult arm cuff using the oscillometric technique in 168 ambulatory outpatients attending a cerebrovascular disease clinic. RESULTS: The mean difference between sequential mean blood pressure readings with the finger cuff was 0.55 mm Hg (95% confidence interval (CI) -14.36 to 15.47 mm Hg), and for the arm cuff was 3.31 mm Hg (95% CI -23.33 to 16.71 mm Hg). Measurements made with the arm cuff were shown to affect subsequent arm cuff readings made within a few minutes of the first. The mean difference between the finger cuff and arm cuff mean blood pressure readings was 0.03 mm Hg (95% CI -26.07 to 26.14 mm Hg) and agreement was better when the blood pressure was measured with the finger cuff first rather than the arm cuff. However, although there was no difference in the mean blood pressure recordings both systolic and diastolic blood pressure measurements differed systematically between arm and finger cuff. CONCLUSION: The reproducibility of sequential blood pressure measurements made with the finger cuff was better than with the arm cuff. The performance of the finger cuff compared with that of the arm cuff was sufficiently good to encourage use of the finger cuff in research involving automatic intermittent monitoring to observe sequential blood pressures over time in stroke patients. However, measurements of systolic and diastolic pressure were not the same with the two cuffs and further work on calibration of the finger cuff would be useful.
Adolescent↗
Qualitative comparison of the reliability of health status assessments with the EuroQol and SF-36 questionnaires after stroke. United Kingdom Collaborators in the International Stroke Trial.
BACKGROUND AND PURPOSE: The reliability of the EuroQol and SF-36 questionnaires after stroke is not known. We therefore aimed to assess and compare the test-retest reliability of both instruments in a group of stroke patients. METHODS: A total of 2253 patients with stroke entered by United Kingdom hospitals in the International Stroke Trial were randomized to follow up with either the EuroQol or the SF-36 instruments. For both instruments, we randomly selected one third of respondents and asked them to complete another, identical questionnaire. We assessed test-retest reliability using agreement statistics: unweighted kappa statistics for the categorical domains of the EuroQol and intraclass correlation coefficients for the EuroQol visual analog scale, utility scores, and SF-36. RESULTS: For the five categorical domains of the EuroQol, reproducibility was generally good (kappa ranged from 0.63 to 0.80). The reproducibility of the domains of the SF-36 was qualitatively similar for all the domains except mental health (intraclass correlation coefficient=.28). However, the 95% confidence intervals for the difference in scores between test and retest were substantial. For both instruments, reproducibility was better when the patient completed the questionnaires than when a proxy did. CONCLUSIONS: Both the EuroQol and SF-36 have acceptable and qualitatively similar test-retest reliability. Therefore, either instrument might function effectively as a discriminatory measure for assessing health-related quality-of-life outcomes in groups of patients after stroke. However, our data do not support the use of either instrument for serial assessments in individual patients unless very large differences over time are expected.
Activities of Daily Living↗
Clinical and angiographic predictors of stroke and death from carotid endarterectomy: systematic review.
OBJECTIVE: To identify risk factors for operative stroke and death from carotid endarterectomy. DESIGN: Systematic review of all studies published since 1980 which related risk of stroke and death to various preoperative clinical and angiographic characteristics, including unpublished data on 1729 patients from the European carotid surgery trial. MAIN OUTCOME MEASURE: Operative risk of stroke and death. RESULTS: Thirty six published studies fulfilled our criteria. The effect of 14 potential risk factors was examined. The odds of stroke and death were decreased in patients with ocular ischaemia alone (amaurosis fugax or retinal artery occlusion) compared with those with cerebral transient ischaemic attack or stroke (seven studies; odds ratio 0.49; 95% confidence interval 0.37 to 0.66; P < 0.00001). The odds were increased in women (seven studies; 1.44; 1.14 to 1.83; P < 0.005), subjects aged > or = 75 years (10 studies: 1.36; 1.09 to 1.71; P < 0.01), and with systolic blood pressure > 180 mm Hg (four studies; 1.82; 1.37 to 2.41; P < 0.0001), peripheral vascular disease (one study; 2.19; 1.40 to 3.60; P < 0.0005), occlusion of the contralateral internal carotid artery (14 studies; 1.91; 1.35 to 2.69; P < 0.0001), stenosis of the ipsilateral internal carotid siphon (five studies; 1.56; 1.03 to 2.36; P = 0.02), and stenosis of the ipsilateral external carotid artery (one study; 1.61; 1.05 to 2.47; P = 0.03). Operative risk was not significantly related to presentation with cerebral transient ischaemic attack versus stroke, diabetes, angina, recent myocardial infarction, current cigarette smoking, or plaque surface irregularity at angiography. Multiple regression analysis of data from the European carotid surgery trial identified cerebral versus ocular events at presentation, female sex, systolic hypertension, and peripheral vascular disease as independent risk factors. CONCLUSIONS: The risk of stroke and death from carotid endarterectomy is related to several clinical and angiographic characteristics. These observations may help clinicians to estimate operative risks for individual patients and will also facilitate more meaningful comparison of the operative risks of different surgeons or at different institutions by allowing some adjustment for differences in case mix.
Aged↗
A randomised comparison of the EuroQol and Short Form-36 after stroke. United Kingdom collaborators in the International Stroke Trial.
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Cerebrovascular Disorders↗
Evaluation of a stroke family care worker: results of a randomised controlled trial.
OBJECTIVE: To examine the effect of contact with a stroke family care worker on the physical, social, and psychological status of stroke patients and their carers. DESIGN: Randomised controlled trial with broad entry criteria and blinded outcome assessment six months after randomisation. SETTING: A well organised stroke service in an Edinburgh teaching hospital. SUBJECTS: 417 patients with an acute stroke in the previous 30 days randomly allocated to be contacted by a stroke family care worker (210) or to receive standard care (207). The patients represented 67% of all stroke patients assessed at the hospital during the study period. MAIN OUTCOME MEASURES: Patient completed Barthel index, Frenchay activities index, general health questionnaire, hospital anxiety and depression scale, social adjustment scale, mental adjustment to stroke scale, and patient satisfaction questionnaire; carer completed Frenchay activities index, general health questionnaire, hospital anxiety and depression scale, social adjustment scale, caregiving bassles scale, and carer satisfaction questionnaire. RESULTS: The groups were balanced for all important baseline variables. There were no significant differences in physical outcomes in patients or carers, though patients in the treatment group were possibly more helpless less well adjusted socially, and more depressed, whereas carers in the treatment group were possibly less hassled and anxious. However, both patients and carers in the group contacted by the stroke family care worker expressed significantly greater satisfaction with certain aspects of their care, in particular those related to communication and support. CONCLUSIONS: The introduction of a stroke family care worker improved patients' and their carers' satisfaction with services and may have had some effect on psychological and social outcomes but did not improve measures of patients' physical wellbeing.
Activities of Daily Living↗
Severe stenosis of the internal carotid artery is not associated with borderzone infarcts in patients randomised in the European Carotid Surgery Trial.
Borderzone infarcts are usually regarded as being caused by low cerebral blood flow distal to a severely stenosed or occluded artery, particularly the internal carotid artery. To explore this hypothesis we have related borderzone infarction, defined by CT both in the classical way and by taking into account the variable extent of the territory of the blood supply of the cerebral arteries, to the severity of any disease of the symptomatic artery in 384 patients in the European Carotid Surgery Trial in whom a scan showing infarction was available. Although there was a tendency for borderzone infarction to occur more often distal to severe carotid disease, this was not significant, and many cases of borderzone infarcts occurred in patients with mild or moderate carotid disease. Therefore, the topography of infarction on CT cannot be used to imply a particular pathophysiology based on the severity of disease of the artery supplying that area of the brain. Severe carotid stenosis is neither sufficient nor necessary to produce borderzone infarction. However, it has to be emphasized that patients with carotid occlusion are not included in this study.
Aged↗
The effect of omeprazole pretreatment on acetaminophen metabolism in rapid and slow metabolizers of S-mephenytoin.
Omeprazole, a widely used and potent gastric proton pump inhibitor, induces cytochrome P450 (CYP) 1A2 in humans. Induction is most pronounced in slow metabolizers of S-mephenytoin because CYP2C19 (S-mephenytoin hydroxylase) is responsible for the elimination of omeprazole. Acetaminophen (INN, paracetamol), a widely used and effective analgesic and antipyretic agent, causes serious hepatic and renal toxicity at high doses by conversion of acetaminophen to the toxic intermediate N-acetyl-p-benzoquinone imine (NAPQI) through CYP1A2, CYP2E1, and CYP3A4. This study evaluated whether omeprazole pretreatment in five rapid and five slow metabolizers of S-mephenytoin could increase thioether (an estimate of NAPQI production) metabolite formation from acetaminophen. The results of this study show that, despite induction of CYP1A2 activity in slow metabolizers (a 75% increase in plasma clearance of caffeine), the formation of NAPQI from acetaminophen was not increased after 7 days of omeprazole administration (40 mg/day). This suggests that induction of CYP1A2 activity by omeprazole is unlikely to increase the risk of acetaminophen hepatotoxicity.
Acetaminophen↗
The simian T-lymphotropic/leukemia virus from Pan paniscus belongs to the type 2 family and infects Asian macaques.
The proviral DNA of the simian T-leukemia/lymphotropic virus (STLV) isolate, originally obtained from a captive colony of pygmy chimpanzees (Pan paniscus) (STLV(pan-p)), was cloned from the DNA of the chronically infected human T-cell line L93-79B. The entire proviral DNA sequence was obtained and compared with sequences of the known genotypes of STLV and human T-leukemia/lymphotropic virus types 1 and 2 (HTLV-1 and -2). Phylogenetic analysis indicates that STLV-2(pan-p) is an early divergence within the type 2 lineage and should be referred to as STLV-2(pan-p). Since STLV-2(pan-p) has been found in African nonhuman primates, we investigated its infectiousness and pathogenicity in Asian monkeys. Pigtailed macaques were inoculated with human cells harboring STLV(pan-p), and infection was assessed by virus isolation, PCR analysis of peripheral blood mononuclear cells, and seroconversion against viral antigens in HTLV-1/HTLV-2 and Western blot assay. Pigtailed macaques became persistently infected by STLV-2(pan-p), and the virus could be transferred by blood transfusion from an infected pigtailed macaque to a rhesus macaque. In addition, like HTLV-1 and HTLV-2, STLV-2(pan-p) was infectious in rabbits. In summary, STLV-2(pan-p) is a novel retrovirus distantly related to HTLV-2 and displays a host range similar to that demonstrated for other HTLV and STLV strains.
Amino Acid Sequence↗
Is the EuroQol a valid measure of health-related quality of life after stroke?
BACKGROUND AND PURPOSE: The EuroQol measures aspects of quality of life that are highly relevant to stroke patients. It is short and simple and many stroke patients can complete the form without help. However, its validity has not been adequately assessed after stroke. We therefore assessed its concurrent and discriminant validity in a group of prospectively studied stroke survivors. METHODS: We assessed the validity of the EuroQol in a series of 152 patients with stroke who were all visited by a study nurse. The nurse gave the patients the EuroQol, the Frenchay Activities Index, a visual analogue pain scale, and the Hospital Anxiety and Depression Scale in the form of questionnaires to be self-completed where possible. The nurse interviewed the patient directly to assess disability using the Office of Population Censuses and Surveys Disability scale and Barthel Index. RESULTS: The nurse assessed 152 patients; of these 92 were able to complete the EuroQol without help, the remaining 60 could only be assessed by interview. The EuroQol had reasonable concurrent validity; median scores on the relevant standard instruments varied significantly (and in the appropriate direction) for groups defined by their response to the relevant EuroQol domain. The EuroQol had reasonable discriminant validity since the responses enabled separation between patients with differing stroke syndromes and stroke severities. Accuracy for predicting outcome after stroke was good for both self-completed and interview-completed questionnaires. CONCLUSIONS: The EuroQol appears to have acceptable concurrent and discriminant validity for the measurement of health-related quality of life after stroke. It may be administered by either a questionnaire for self-completion in patients with mild to moderate stroke or by interview in patients with significant motor deficits.
Aged↗
Are proxy assessments of health status after stroke with the EuroQol questionnaire feasible, accurate, and unbiased?
BACKGROUND AND PURPOSE: It is often difficult to determine the health-related quality of life (HRQoL) of stroke patients because physical and cognitive problems limit their ability to complete complex questionnaires. A proxy, such as a family member or caregiver, may be able to give an estimate of the patients' health status. We therefore examined the agreement between the HRQoL as assessed by a series of patients and that assessed by their proxies. METHODS: We studied the validity of the EuroQol in a series of 152 patients from our prospective registry of patients with first (or recurrent) stroke. We asked patients to ensure that a friend or relative (a proxy) who knew them well was available at the time of the interview. We asked each proxy to complete a EuroQol questionnaire independently on behalf of the patient. RESULTS: Proxies completed forms for 130 patients (86%). Agreement between responses from the patients and those from their proxies was better for patients who were able to self-complete the EuroQol than for patients who required the EuroQol to be administered by interview. For both groups, agreement was best for the self-care domain and worst for the domain that assessed psychological outcome. For the more severely affected patients, agreement was only fair for the pain and social functioning domains and no better than chance alone for the psychological functioning domain (kappa = 0.05, 95% confidence interval, 0 to 0.43). Patients tended to rate their own health status as better than their proxies did (P < .05). CONCLUSIONS: We found moderate agreement between responses from patients and those from their proxies for the more directly observable domains of the EuroQol. Proxy agreement was less good for the more subjective domains. In health surveys, allowing responses by a proxy increases response rate. However, the disadvantages inherent in the use of proxy responses must be considered carefully. In general, some domains of HRQoL information obtained from a proxy may be sufficiently valid and unbiased to be useable in most types of trials and surveys.
Caregivers↗
Nonhypertensive cerebral small-vessel disease. An autopsy study.
BACKGROUND AND PURPOSE: Cerebral small-vessel disease (SVD) is a common aging phenomenon that is exacerbated by hypertension and diabetes mellitus. It is regarded as an important cause of lacunar infarction and intracerebral hemorrhage. The present study was performed to highlight the existence and to some extent the frequency of pathologically verified SVD lacking in classic risk factors and to extend the scope of risk factor analysis. METHODS: The study group comprised 70 consecutively referred autopsy brains with microscopic evidence of SVD. In each case clinical records, autopsy reports, and central nervous system and systemic autopsy histology were reviewed. SVD was graded as mild, moderate, or severe in six standardized brain regions, and the results analyzed in relation to the presence or absence of classic SVD risk factors. RESULTS: SVD was manifest largely as concentric hyaline wall thickening; lipohyalinosis and fibrinoid necrosis were rarely observed. Thirty-one percent of cases failed to meet stringent clinicopathological criteria for significant prior hypertension. In 9% of cases, patients had been nonelderly, nondiabetic, and normotensive. Five of six cases lacking classic risk factors had systemic conditions known to enhance small-vessel permeability. CONCLUSIONS: The nature of SVD appears to have been modified by effective treatment of hypertension. Classic risk factors are often absent. The hypothesis that a variety of conditions that enhance small-vessel permeability may contribute to the pathogenesis of SVD merits consideration.
Aged↗
Chemotherapy response criteria in malignant glioma.
No one has ever proven a relationship between the extent of response to chemotherapy in malignant glioma and time to progression or survival. We studied the predictive value of "imaging response" following two courses of nitrosourea-based chemotherapy in 136 patients with recurrent astrocytoma/malignant glioma. We performed image analysis by blinded side-to-side comparison of sequential studies, and categorized response into: partial response (PR) (>50% reduction), minor response (MR) (25-50% reduction), stable disease (SD) (<25% change), progressive disease (PD) (>25% increase). Patients with PR, MR, and SD did not differ with respect to time to progression (TTP) (p > 0.2) or survival (p > 0.2). Median TTP was 27 weeks for SD, 43 weeks for MR, and 30 weeks for PR. Patients with PD had a significantly reduced survival (p < 0.001). Median survival was 21 weeks for PD, 53 weeks for SD, 63 weeks for MR, and 48 weeks for PR. The lack of relationship between response and TTP may be due to early relapses in patients with response, a cytostatic benefit of chemotherapy in some patients who do not have an objective response, or a relatively favorable natural history in some tumors that do not respond to chemotherapy. Our data do not support the validity of current response grading, assessed after two courses of chemotherapy. Further research and validation of response criteria is necessary.
Adolescent↗
Blood pressure and risk of stroke in patients with cerebrovascular disease. The United Kingdom Transient Ischaemic Attack Collaborative Group.
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Aspirin↗
Is stroke incidence related to season or temperature? The Oxfordshire Community Stroke Project.
BACKGROUND: A winter excess of ischaemic stroke has been found in mortality and hospital-based studies. It is often assumed that this is due to seasonal variation in stroke incidence and several pathophysiological explanations have been proposed. We studied the incidence of stroke in relation to season and outside temperature. METHODS: The data came from a community-based study of first ever in a lifetime stroke in a defined population of about 105 000. 675 such strokes were registered over four years and the month of inset was analysed separately for cerebral infarction, primary intracerebral haemorrhage, and subarachnoid haemorrhage. FINDINGS: There was no significant seasonal variation. The incidence of primary intracerebral haemorrhage was increased at low temperatures, but there was no significant relation between the incidence of ischaemic stroke or subarachnoid haemorrhage and temperature. INTERPRETATION: The widely reported winter excess of ischaemic strokes may be an artifact due to referral bias in hospital-based studies and increased case fatality during the winter in mortality studies.
Cerebral Hemorrhage↗