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Biomedical subjects

D J Stott

Publications and source records attributed to D J Stott.

At least 37 records · Page 2Linked to original sources

The design of a prospective study of Pravastatin in the Elderly at Risk (PROSPER). PROSPER Study Group. PROspective Study of Pravastatin in the Elderly at Risk.

The PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) is a randomized, double-blind, placebo-controlled trial designed to test the hypothesis that treatment with pravastatin will diminish risk of subsequent major vascular events in a cohort of men and women (70 to 82 years old) with preexisting vascular disease or significant risk of developing this condition. Five thousand eight hundred four men and women in addition to receiving advice on diet and smoking, have been randomized equally to treatment with 40 mg pravastatin/day or matching placebo in 3 centers (Cork, Ireland, Glasgow, Scotland, and Leiden, The Netherlands). Following an average 3.5-year intervention period, a primary assessment will be made of the influence of this therapy on major vascular events (a combination of coronary heart disease, death, nonfatal myocardial infarction, and fatal and nonfatal stroke). A number of additional analyses will also be conducted on the individual components of the primary end point, on men, on women, and on subjects with and without previous evidence of vascular disease. Finally, an assessment will be made of the effects of treatment on cognitive function, disability, hospitalization or institutionalization, vascular mortality, and all-cause mortality.

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Swallowing abnormalities after acute stroke: A case control study.

Dysphagia is a common and potentially fatal complication of acute stroke. However, the underlying pathophysiology, especially the relative importance of motor and sensory dysfunction, remains controversial. We conducted a case control study of 23 acute stroke patients (mean age = 72 yr) at a median of 6 days post-stroke and 15 healthy controls (mean age = 76 yr). We used novel methods to assess swallowing in detail, including a timed videoendoscopic swallow study and oral sensory threshold testing using electrical stimulation. Vocal cord mobility and voluntary pharyngeal motor activity were impaired in the stroke group compared with the controls (p = 0.01 and 0.03). There was a delay during swallowing in the time to onset of epliglottic tilt in the stroke group, particularly for semisolids (p = 0.02) and solids (p = 0.01), consistent with a delay in initiation of the swallow. Sensory thresholds were not increased in the stroke group compared with controls. We conclude that pharyngeal motor dysfunction and a delay in swallow initiation are common after acute stroke. Vocal cord mobility is reduced, and this may result in reduced airway protection. We found no evidence to support the hypothesis that oropharyngeal sensory dysfunction is common after acute stroke.

Acute Disease↗

Influenza diagnosis: from dark isolation into the molecular light. West of Scotland Respiratory Virus Study Group.

OBJECTIVES: To compare the conventional virus isolation method for diagnosis of influenza infection with reverse-transcription polymerase chain reaction (RT-PCR) in prospectively collected nose and throat swabs from elderly patients during the winter influenza season. The use of a denaturing buffer as an alternative to viral transport medium (VTM) for submission of combined nose and throat swabs to the laboratory for PCR was then investigated in a second study. METHODS: Virus was cultured in microtitre plates using two different cell lines and detected using monoclonal antibody staining. A multiplex, matrix gene PCR assay was optimized to increase the sensitivity and specificity of detection of influenza A (H3 and H1) and B nucleic acid. RESULTS: The multiplex assay detected all viruses with equal sensitivity to individual assays. In a large, multicentre field study PCR detected twice as many influenza infections compared with virus isolation. No positive culture was missed. PCR has a rapid turn around time (< 36 h) vs. a minimum of 7 days for virus isolation. Greater sensitivity and specificity in the PCR were achieved using a 'hot-start' method. Although the numbers were small, the detection rate using PCR was greater for swabs submitted in denaturing buffer than in VTM. CONCLUSIONS: PCR significantly increased the sensitivity and clinical utility of influenza A (H3 and H1) and B diagnosis. There were a number of advantages in using denaturing buffer for submission of samples, including high sensitivity, rapidity, ease of use and no requirement for the virus to be viable on arrival at the laboratory. Therefore, PCR is a rapid, sensitive and user-friendly alternative for influenza diagnosis. Virus isolation technology should be limited to referral centres for further epidemiological characterization.

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Serological response to influenza vaccination and nutritional and functional status of patients in geriatric medical long-term care.

INTRODUCTION: in the UK the Department of Health recommends influenza vaccination for elderly people resident in institutional care. However, the efficacy of vaccination may be reduced in very frail elderly people with functional impairment, undernutrition and multiple pathologies. Nutritional and functional status is claimed to affect vaccine responses in healthy elderly subjects. We wished to determine if a relationship could be seen between nutritional and functional status and seroconversion in patients receiving long- term care. METHODS: all patients in geriatric medical long-term care were offered vaccine. Consenting patients had pre- and post-vaccine serology measured using single radial haemolysis. Anthropometry was measured to enable body mass index (BMI) to be calculated. Functional independence was assessed using the 20-point Barthel index. RESULTS: of 260 patients who received influenza vaccine, 137 (36 male, 101 female) consented to venesection for serology and thus form the study population. Mean age was 82 years (SD 7.9). The median Barthel score was 3/20 and the mean BMI was 21.6 (SD 4.6, range 13-36.2). Antibodies to influenza A were undetectable both pre- and post-vaccination in 63/137 patients. In 49 patients the antibody titre rose after vaccination and 25 had detectable antibody titres pre-vaccination which failed to rise post-vaccine. There were no significant associations between post-vaccination influenza antibody responses and BMI, Barthel score or age. CONCLUSION: frail elderly patients in geriatric medical long-term care had a poor antibody response to influenza vaccination. Within this group, serological responses could not be predicted by nutritional or functional status.

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Electrical stimulation of wrist extensors in poststroke hemiplegia.

BACKGROUND AND PURPOSE: It has been suggested that cyclic neuromuscular electrical stimulation (ES) may enhance motor recovery after stroke. We have investigated the effects of ES of the wrist extensors on impairment of wrist function and on upper-limb disability in patients being rehabilitated after acute stroke. METHODS: We recruited 60 hemiparetic patients (mean age, 68 years) 2 to 4 weeks after stroke into a randomized, controlled, parallel-group study comparing standard rehabilitation treatment with standard treatment plus ES of wrist extensors (3 times 30 minutes daily for 8 weeks). Isometric strength of wrist extensors was measured using a device built for that purpose. Upper-limb disability was assessed with use of the Action Research Arm Test (ARAT). Observations were continued for 32 weeks (24 weeks after the finish of ES or the control intervention phase). RESULTS: The change in isometric strength of wrist extensors (at an angle of 0 degrees extension) was significantly greater in the ES group than the control group at both 8 and 32 weeks (P=0.004, P=0.014 by Mann Whitney U test). At week 8 the grasp and grip subscores of the ARAT increased significantly in the ES group compared with that in the control group (P=0.013 and P=0.02, respectively); a similar trend was seen for the total ARAT score (P=0.11). In the subgroup of 33 patients with some residual wrist extensor strength at study entry (moment at 0 degrees extension >0), the ARAT total score had increased at week 8 by a mean of 21.1 (SD, 12.7) in the ES group compared with 10.3 (SD, 9.0) in the control group (P=0.024, Mann Whitney U test); however, at 32 weeks the differences between these 2 subgroups were no longer statistically significant. CONCLUSIONS: ES of the wrist extensors enhances the recovery of isometric wrist extensor strength in hemiparetic stroke patients. Upper-limb disability was reduced after 8 weeks of ES therapy, with benefits most apparent in those with some residual motor function at the wrist. However, it is not clear how long the improvements in upper-limb disability are maintained after ES is discontinued.

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Prevalence and haemopoietic effects of low serum vitamin B12 levels in geriatric medical patients.

The clinical significance of low serum vitamin B12 levels in elderly people is controversial. We aimed to document the prevalence of a low serum vitamin B12 (< 175 pmol/l) in patients referred to a geriatric medical unit, and to determine whether haemopoiesis is commonly affected in elderly patients with low serum vitamin B12. We studied prospectively 472 consecutive referrals to a geriatric medical unit; fifty-six (13%) had a low serum vitamin B12 level, of whom nineteen (34%) of the fifty-six also had evidence of Fe deficiency (serum ferritin < 45 ng/ml). Low vitamin B12 was associated with a raised mean erythrocyte volume (MCV; mean 96.0 (SD 6.7) fl), compared with a control group (91.7 (SD 6.0) fl; P = 0.001). However, only thirteen (23%) of the fifty-six patients with a low vitamin B12 had an MCV > or = 100 fl. Mean haemoglobin (Hb) levels were not significantly reduced in those with a low vitamin B12. In a subsequent study the haematological response to intramuscular hydroxocobalamin was examined in thirty-four patients with a low serum vitamin B12. Treatment resulted in a significant fall in MCV and rise in Hb; these effects could be detected both in those patients with an initially normal full blood count (change in MCV -1.2 (SD 1.2); Hb +0.5 (SD 0.6); P < 0.01) and in those with macrocytosis and/or anaemia (-9.1 (SD 11.8); +0.8 (SD 1.2); P < 0.05). A low serum vitamin B12 is common in geriatric medical patients. This is usually associated with an upset in erythropoiesis, although the abnormalities are often subtle and may not be apparent on inspection of the full blood count. Elderly patients with serum vitamin B12 < 175 pmol/l should be assumed to have vitamin deficiency even if their full blood count is normal.

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Influenza vaccination of health care workers in long-term-care hospitals reduces the mortality of elderly patients.

Vaccination of health care workers (HCWs) is recommended as a strategy for preventing influenza in elderly patients in long-term care. However, there have been no controlled studies to show whether this approach is effective. During the winter of 1994-1995, 1059 patients in 12 geriatric medical long-term-care sites, randomized for vaccination of HCWs, were studied. In hospitals where HCWs were offered vaccination, 653 (61%) of 1078 were vaccinated. Vaccination of HCWs was associated with reductions in total patient mortality from 17% to 10% (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.40-0.80) and in influenza-like illness (OR, 0.57; 95% CI, 0.34-0.94). Vaccination of patients was not associated with significant effects on mortality (OR, 1.15; 95% CI, 0.81-1.64). Results of this study support recommendations for vaccination against influenza of HCWs in long-term geriatric care. Vaccination of frail elderly long-term-care patients may not give clinically worthwhile benefits.

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Effects of electrical stimulation on flexion contractures in the hemiplegic wrist.

OBJECTIVE: To study the effects of electrical stimulation (ES) on flexion contractures in the hemiplegic wrist. DESIGN: The investigation was carried out following an OFF (two weeks with rehabilitation only)--ON (two weeks with ES treatment and rehabilitation)--OFF (two weeks rehabilitation only) fixed protocol. SETTING: A stroke ward and an outpatient stroke service. SUBJECTS: Eleven hemiplegic subjects with reduced range of extension and increased resistance to passive movement at the wrist. MAIN MEASURE: Quantitative measures of the hemiplegic posture at the wrist, passive range of extension and resistance to passive extension of the wrist. Measurements were taken at the start of the study and then at two-weekly intervals. Two extra measurements were taken at the end of the ON period. RESULTS: Following two weeks treatment with ES the posture of the wrist improved and the passive range of extension increased. However, there were no significant changes in the resistance to passive movement. These benefits appeared largely to be lost two weeks after ES was discontinued. CONCLUSIONS: Short-term ES gives temporary improvements in contractures at the wrist in poststroke hemiplegia.

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Effects of captopril and enalapril on renal function in elderly patients with chronic heart failure.

OBJECTIVE: To compare the effects on renal function of captopril and enalapril in elderly patients with chronic heart failure. DESIGN: A multi-centre double-blind parallel-group comparison of the two angiotensin-converting enzyme (ACE) inhibitors, captopril (12.5 mg bid) and enalapril (2.5 mg bid). SUBJECTS: 80 elderly patients with chronic heart failure (41 in the captopril group, 39 in the enalapril group). MAIN OUTCOME MEASURES: The blood pressure and pulse rate response to the first dose of ACE inhibitor was assessed in all patients. Glomerular filtration rate (GFR) was measured radioisotopically by 99mTcDTPA or 51CrEDTA clearance after three and six months of each treatment. Subgroups were assessed for effective renal plasma flow (33 patients), exercise tolerance (25 patients) and by a symptom-oriented questionnaire (45 patients). RESULTS: No serious adverse effect on GFR was noticed. There was no significant difference between the two treatments in the mean baseline GFR or in changes from baseline at three and six months (captopril mean baseline GFR 49.6 ml min-1 1.76 m-2, enalapril 54.7 ml min-1 1.76 m-2; mean change (95% confidence interval) at three months captopril 12 ml min-1 (+3.0, +21.0), enalapril -2 ml min-1 (-13.0; +9.0); mean change at six months, captopril 3.7 ml min-1 (-6.7; +14.2), enalapril -6.0 ml min-1 (-21.0; +9.4). Significantly more patients given captopril had an improvement in GFR during the study period (26/31 compared with 20/31 enalapril-treated patients at three months, p = 0.0096, and 23/30 compared with 15/27 at six months, p = 0.021). There were no significant changes in effective renal plasma flow. Three patients treated with enalapril developed symptomatic hypotension within three days of starting treatment. Quality of life questionnaires revealed more gastrointestinal symptoms in the enalapril group (p = 0.039). CONCLUSIONS: Captopril seems marginally preferable to enalapril in the treatment of chronic heart failure in elderly patients.

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Acute cerebral infarction. Optimal management in older patients.

The optimal management of acute cerebral infarction requires consideration of the diagnosis, aetiology, identification of problems, general and specific aspects of care, and prevention of further vascular events. Stroke is a clinical diagnosis but cranial computed tomography (CT) scanning is invaluable to exclude the possibility of cerebral haemorrhage or where the diagnosis is uncertain. Good general care under a specialist multidisciplinary team can reduce mortality and the need for institutional care. Despite promising results from experimental studies, no routine drug therapies have yet shown clinical benefit in acute stroke. Several large trials are currently evaluating anticoagulant, antiplatelet, thrombolytic and neuroprotective agents. Many other proposed therapies have been subject to limited evaluation. Aspirin has a proven role in the prevention of further vascular events after a stroke or transient ischaemic attack. Warfarin, and to a lesser extent aspirin, can prevent recurrent events in patients with nonrheumatic atrial fibrillation. Concerns remain about the safety of warfarin in routine geriatric medical practice. The risk of recurrent stroke in patients with a symptomatic severe carotid artery stenosis is greatly reduced by endarterectomy.

Aging↗

Use of plasma ferritin concentration to diagnose iron deficiency in elderly patients.

AIMS: To determine a concentration of ferritin below which the possibility of iron deficiency should be considered in elderly patients. METHODS: Consecutive new referrals to a geriatric unit (n = 472) were studied prospectively. Full blood count, ferritin, serum vitamin B12 and red cell folate were measured for all patients. A blood film was assessed independently by three haematologists for features of iron deficiency. For those with ferritin of 12-45 ng/ml, bone marrow aspirates were performed and examined for the presence of stainable iron. When possible, a trial of oral iron was given to those with ferritin of < or = 45 ng/ml and response was determined by re-measurement of full blood count and ferritin after a minimum of three weeks of treatment. RESULTS: Bone marrow examination was performed in 32 patients with ferritin of 12-45 ng/ml, of whom 27 (84%) had absent stainable iron, suggesting that most elderly patients with ferritin in this range have iron deficiency. Compared with those with ferritin of 100-299 ng/ml, in whom iron stores were presumed to be normal, patients with ferritin of 12-45 ng/ml had a significantly lower mean haemoglobin and mean red blood cell volume. Furthermore, patients with ferritin up to 75 ng/ml had a significantly higher mean red cell distribution width, and were more likely to have an iron deficient blood film. CONCLUSION: Iron deficient erythropoiesis can occur in elderly patients with ferritin up to 75 ng/ml. This is much higher than the lower limit of the "normal" range usually quoted for younger subjects; this difference should be taken into account when ferritin concentrations are interpreted in elderly patients.

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Use of the erythrogram in the diagnosis of iron deficiency in elderly patients.

In elderly patients the diagnosis of iron deficiency from full blood count indices is often difficult. We assessed an automated technique (numerical data of the erythrogram; Technicon H*1) by which the proportions of microcytic (< 60 fl) and/or hypochromic (< 28 g.dl-1) red blood cells are determined. Of 472 elderly patients investigated, 100 (21%) were found to have iron deficiency (plasma ferritin < or = 45 ng.ml-1). Less than two-thirds of patients with iron-deficient erythropoiesis (anaemia or microcytosis) had increased proportions of hypochromic and/or microcytic red blood cells. Furthermore, the erythrogram was not sensitive in detecting latent or early iron deficiency. The erythrogram also lacked specificity for iron deficiency anaemia as many patients with mild normocytic anaemia associated with chronic inflammatory disease had increased proportions of hypochromic and/or microcytic red blood cells. Although patients with iron deficiency had increased proportions of hypochromic normocytic (p < 0.01) and normochromic microcytic red blood cells (p < 0.05) compared to those with chronic inflammatory disease and normal or raised iron stores (ferritin > or = 100 ng.ml-1, n = 32), there was a large overlap between these two groups, and the grossly elevated erythrogram results in patients with iron deficiency were almost always associated with a mean cell volume (MCV) < 80 fl, whereas none of the patients with chronic inflammatory disease and normal or raised iron stores had an MCV < 80 fl. Thus the erythrogram does not appear to be of value in the routine assessment of iron status in elderly patients.

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Terodiline causes polymorphic ventricular tachycardia due to reduced heart rate and prolongation of QT interval.

Recent reports have suggested an association between terodiline hydrochloride and cardiac arrhythmias. We report 4 patients presenting over a six month period who developed polymorphic ventricular tachycardia (polymorphic VT) while receiving treatment with this agent. In each case there was prolongation of QT interval on electrocardiogram (ECG). Two patients had hypokalaemia associated with diuretic therapy. In the 3 cases in which follow-up ECG was available, QT interval returned to normal after discontinuation of terodiline. In order to define the effects of terodiline on corrected QT interval (QTc) and heart rate in the elderly, a prospective study was performed in 8 elderly in-patients treated with terodiline for urinary incontinence. After 7 days treatment with terodiline 12.5 mg twice daily, there was a significant increase in QT by a mean of 29 ms, QTc by 15 ms and a decrease in resting heart rate by a mean of 6.7 beats.min-1. Terodiline increases QTc and reduces resting heart rate in elderly patients. Both these effects may be associated with polymorphic VT, a potentially life threatening arrhythmia. This drug should be avoided in patients with other known risk factors for polymorphic VT, particularly hypokalaemia and cardiac disease.

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