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Biomedical subjects

S Ebrahim

Publications and source records attributed to S Ebrahim.

At least 37 records · Page 2Linked to original sources

The effect of the C677T and A1298C polymorphisms in the methylenetetrahydrofolate reductase gene on homocysteine levels in elderly men and women from the British regional heart study.

Total blood levels of homocysteine (tHcy) have been shown to depend on both environmental and genetic factors, and to be associated with the risk of developing atherosclerosis with its complications of coronary heart disease (CHD) and stroke. In this study, 408 men and 346 women from two towns, Dewsbury and Maidstone were examined for tHcy levels and genotyped for the C677T and the A1298C polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene. Blood tHcy was significantly higher in men from the CHD high risk town of Dewsbury (12.7 micromol/l) than in the low CHD risk town of Maidstone (11.5 micromol/l) P<0.001, but not in women (10.7 vs. 10.5 micromol/l), with women in both towns, thus, showing significantly lower tHcy than men. There was no difference between towns in folate or vitamin B12 levels but the conventional inverse relationship with tHcy was seen. Smoking men and women from both towns had significantly higher tHcy and lower folate levels than non-smoking individuals (P<0.001). The frequency of the 677T allele in Dewsbury was 0.35 (95% CI; 0.32-0.39) compared with 0.29 (95% CI; 0.26-0.32) in Maidstone (P<0.01). Similar frequency difference of borderline statistical significance was seen both for men (P=0.054) and women (P=0.048) in both the towns, suggesting a true regional frequency difference. The effect of the 677T on tHcy was highly significant in the group as a whole with the most profound effect seen in men (12.0 micromol/l for CC vs. 14.1 micromol/l for TT, P<0.001). By contrast, there was no significant effect of the A1298C polymorphism on tHcy, folate or vitamin B12 levels, with no evidence for an interaction with the C677T genotype. The regional differences in tHcy levels were still present after the adjustment for folate and vitamin B12 levels, smoking and the effect of the C677T polymorphism. This suggests that there may be other unidentified factors, either environmental or genetic, affecting tHcy levels, and thus potentially having an impact on the risk of developing hyperhomocysteinaemia and CHD. These observations may have a bearing on regional differences in tHcy levels and the variation in CHD risk between regions in the UK.

Aged↗

Systematic review of long term anticoagulation or antiplatelet treatment in patients with non-rheumatic atrial fibrillation.

OBJECTIVE: To examine the benefits and risks of long term anticoagulation (warfarin) compared with antiplatelet treatment (aspirin/indobufen) [corrected] in patients with non-rheumatic atrial fibrillation. METHODS: Meta-analysis of randomised controlled trials from Cochrane library, Medline, Embase, Cinhal, and Sigle from 1966 to December 1999. Odds ratios (95% confidence intervals) calculated to estimate treatment effects. OUTCOME MEASURES: Fatal and non-fatal cardiovascular events, reductions of which were classified as benefits. Fatal and major non-fatal bleeding events classified as risks. RESULTS: No trials were found from before 1989. There were five randomised controlled trials published between 1989-99. There were no significant differences in mortality between the two treatment options (fixed effects model: odd ratio 0.74 (95% confidence interval 0.39 to 1.40) for stroke deaths; 0.86 (0.63 to 1.17) for vascular deaths). There was a borderline significant difference in non-fatal stroke in favour of anticoagulation (0.68 (0.46 to 0.99)); and 0.75 (0.50 to 1.13) after exclusion of one trial with weak methodological design. A random effects model showed no significant difference in combined fatal and non-fatal events (odds ratio 0.79 (0.61 to 1.02)). There were more major bleeding events among patients on anticoagulation than on antiplatelet treatment (odds ratio 1.45 (0.93 to 2.27)). One trial was stopped prematurely after a significant difference in favour of anticoagulation was observed. The only trial to show a significant difference in effect (favouring anticoagulation) was methodologically weaker in design than the others. CONCLUSIONS: The heterogeneity between the trials and the limited data result in considerable uncertainty about the value of long term anticoagulation compared with antiplatelet treatment. The risks of bleeding and the higher cost of anticoagulation make it an even less convincing treatment option.

Anticoagulants↗

Dietary advice given by a dietitian versus other health professional or self-help resources to reduce blood cholesterol.

BACKGROUND: The average level of blood cholesterol is an important determinant of the risk of coronary heart disease. Blood cholesterol can be reduced by dietary means. Although dietitians are trained to provide dietary advice, for practical reasons it is also given by other health professionals and occasionally through the use of self-help resources. OBJECTIVES: To assess the effects of dietary advice given by a dietitian compared with another health professional, or the use of self-help resources, in reducing blood cholesterol in adults. SEARCH STRATEGY: We searched The Cochrane Library (to Issue 2 1999), MEDLINE (1966 to January 1999), EMBASE (1980 to December 1998), Cinahl (1982 to December 1998), Human Nutrition (1991 to 1998), Science Citation Index, Social Sciences Citation Index, hand searched conference proceedings on nutrition and heart disease, and contacted experts in the field. SELECTION CRITERIA: Randomised trials of dietary advice given by a dietitian compared with another health professional or self-help resources. The main outcome was difference in blood cholesterol between dietitian groups compared with other intervention groups. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed study quality. MAIN RESULTS: Eleven studies with 12 comparisons were included, involving 704 people receiving advice from dietitians, 486 from other health professionals and 551 people using self-help leaflets. Four studies compared dietitian with doctor, seven with self-help resources, and one compared dietitian with nurse. Participants receiving advice from dietitians experienced a greater reduction in blood cholesterol than those receiving advice only from doctors (-0.25 mmol/L (95% CI -0.37, -0.12 mmol/L)). There was no statistically significant difference in change in blood cholesterol between dietitians and self-help resources (-0.10 mmol/L (95% CI -0.22, 0.03 mmol/L)). No statistically significant differences were detected for secondary outcome measures between any of the comparisons with the exception of dietitian versus nurse for HDLc, where the dietitian groups showed a greater reduction (-0.06 mmol/L (95% CI -0.11, -0.01)). No significant heterogeneity between the studies was detected. REVIEWER'S CONCLUSIONS: Dietitians were better than doctors at lowering blood cholesterol in the short to medium term, but there was no evidence that they were better than self-help resources. The results should be interpreted with caution as the studies were not of good quality and the analysis was based on a limited number of trials. More evidence is required to assess whether change can be maintained in the longer term. There was no evidence that dietitians provided better outcomes than nurses.

Cholesterol↗

Hypothermia to reduce neurological damage following coronary artery bypass surgery.

BACKGROUND: Coronary artery bypass surgery (CABG) may be life saving, but known side effects include neurological damage and cognitive impairment. The temperature used during cardiopulmonary bypass (CPB) may be important with regard to these adverse outcomes, where hypothermia is used as a means of neuroprotection. OBJECTIVES: To assess the effectiveness of hypothermia during CABG in reducing neurological damage and subsequent cognitive deficits. SEARCH STRATEGY: The Cochrane Controlled Trials Register was searched for randomised controlled trials (RCT) and this was updated by searching MEDLINE and EMBASE to December 1999 using database specific RCT filters. Reference lists of retrieved articles were searched and experts in the field were contacted. SELECTION CRITERIA: Only RCTs were considered. All patients undergoing CABG, either first time or revisions, elective or emergency procedures, were included. Any hypothermia protocol was considered. Only trials reporting neurological outcomes were included. DATA COLLECTION AND ANALYSIS: Studies were selected independently and data were extracted from the source papers independently by two reviewers. Authors were contacted for further information. Studies were combined with meta-analysis where appropriate, and meta-regression was used to explore heterogeneity. MAIN RESULTS: There was a trend towards a reduction in the incidence of non fatal strokes in the hypothermic group (OR 0.68 (0.43, 1.05)). Conversely, there was a trend for the number of non stroke related perioperative deaths to be higher in the hypothermic group (OR 1.46 (0.9, 2.37)). Hypothermia had no effect on the incidence of non fatal myocardial infarction (OR 1.05 (0.81, 1.37)), but the incidence of another marker of myocardial damage, low output syndrome, was higher in the hypothermic group (OR 1.21 (0.99, 1.48). When pooling all "bad" outcomes (stroke, perioperative death, myocardial infarction, low output syndrome, intra aortic balloon pump use) there was no significant advantage of either hypothermia or normothermia (OR 1.07 (0.92, 1.24)). Only 4 of 17 trials reported neuropsychological function as an outcome. REVIEWER'S CONCLUSIONS: This review could find no definite advantage of hypothermia over normothermia in the incidence of clinical events. Hypothermia was associated with a reduced stroke rate, but this is off set by a trend towards an increase in non stroke related perioperative mortality and myocardial damage. There is insufficient data to date to draw any conclusions about the use of mild hypothermia. Similarly, there is insufficient data to date to comment on the effect of temperature during CPB on subtle neurological deficits, and further trials are needed in these areas.

Cardiac Output, Low↗

Primary mucinous adenocarcinoma of the vagina.

OBJECTIVE: Our goal was to report the management and symptoms of a patient who presented with primary mucinous adenocarcinoma of the vagina with an unusual histologic pattern. METHODS: Our methods included a retrospective description of the management, a review of the literature, and critical evaluation of the treatment modalities available for this very uncommon tumor. RESULTS: Initially posterior partial vaginectomy and abdominoperineal resection was performed with the creation of a permanent colostomy. A bilateral inguinal lymphadenopathy was performed 6 months later on the basis of a palpable enlarged lymph node. Radiotherapy was instituted thereafter. The patient remains disease-free 48 months after initial surgery and is satisfied with her quality of life. CONCLUSIONS: Primary mucinous adenocarcinoma of the vagina is a very rare tumor. Therefore individualized treatment is justified until larger series have been published.

Adenocarcinoma, Mucinous↗

The incidence and aetiology of stroke in the Caerphilly and Speedwell Collaborative Studies I: methods and incidence of events.

Stroke mortality and morbidity remain high despite downward trends in incidence and case fatality. Population-based longitudinal studies which include collection of risk factor data are required for a better understanding of stroke aetiology. From a representative cohort of men from South Wales and South-west England, followed up for a median of 17 y, details of possible cerebrovascular events were collected from questionnaires, hospital admission data, general practitioner records, death certificates, radiology records and post-mortem reports. Radiology records, and strokes and transient ischaemic attacks were independently validated. There were 433 strokes and 163 transient ischaemic attacks identified during follow-up. Of these, 333 were the first ever in a lifetime strokes of which 139 were definite ischaemic, 20 were haemorrhagic and 168 were probable ischaemic strokes. The crude incidence rate for stroke was 445 (95% confidence interval 398-493) per 100 000 person years. The age-standardised rates for 10 y age-bands were: 45-54 y 91 (10-172); 55-64 y 351 (269-432) and 65-74 y 855 (669-1040). The 30 d case-fatality rate was 21.0% (70/333) for all strokes and 19.2% (60/312) for ischaemic strokes. For transient ischaemic attacks the age-standardised incidence rates for the same 10 y age bands were 92 (4-179), 111 (64-157), and 273 (167-80), respectively. These rates for stroke transient ischaemic attack are likely to be accurate given the high ascertainment of events in this representative population of middle-aged men. Such studies, reporting reliable measures of cerebrovascular events, are important for measuring burden of disease, and for analysis of risk factor associations to help improve understanding of stroke aetiology and inform preventive efforts.

Cohort Studies↗

The incidence and aetiology of stroke in the Caerphilly and Speedwell Collaborative Studies II: risk factors for ischaemic stroke.

Reduction of stroke burden requires preventive interventions targeted at important risk factors. This report presents the analysis of risk factors for ischaemic stroke from a representative cohort of middle aged men from South Wales and south-west England. Data on risk factors were collected through validated questionnaires and physical and clinical measurements. Details of possible cerebrovascular events were retrieved, classified into ischaemic, haemorrhagic and uncertain subtypes, and validated. The ratio of definite ischaemic to definite haemorrhagic strokes was calculated. This showed that the vast majority of strokes of unknown subtype were likely to ischaemic. After exclusion of known haemorrhagic strokes and subarrachnoid haemorrhages the remaining strokes were labelled ischaemic. Hazard ratios for possible risk factors were calculated for all ischaemic, and for fatal and non-fatal strokes. There were 293 ischaemic strokes. Statistically significant age-adjusted hazard ratios were: 1.50 (95% confidence interval 1.16-1.95) for being in a manual social class, 1.82 (1.24-2.67) if smoking >15 cigarettes/d at enrollment, 1.19 (1.13-1.24) and 1.23 (1.14-1.34) per 10 mmHg increase in systolic and diastolic blood pressure, respectively, 0.67 (0.46-0.96) for the top quintile high density lipoprotein-cholesterol:cholesterol ratio compared to the bottom quintile, 2.04 (1.40-2.99) for presence of angina, 3.90 (2.01-7.58) for presence of atrial fibrillation, and 3.35 (1.90-5.80) for presence of diabetes. Risk factors were more strongly associated with fatal than non-fatal strokes. Multivariate analyses revealed that, while there was some attenuation of the effect of social class, angina and elevated BP, the risks from atrial fibrillation and diabetes were increased.

Brain Ischemia↗

Is the prevalence of coronary heart disease falling in British men?

OBJECTIVE: To assess whether long term trends over time in acute coronary heart disease (CHD) event rates have influenced the burden of prevalent CHD in British men. DESIGN: Longitudinal cohort study. PARTICIPANTS: 7735 men, aged 40-59 at entry (1978-80), selected from 24 British towns. METHODS: The prevalences of current angina symptoms and history of diagnosed CHD were ascertained by questionnaire in 1978-80, 1983-85, 1992, and 1996. New major CHD events (fatal and non-fatal) were ascertained throughout the study from National Health Service central registers and general practice record reviews. Age adjusted trends in CHD prevalence were compared with trends in major CHD event rates. RESULTS: From 1978-1996 there was a clear decline in the prevalence of current angina symptoms: the age adjusted annual percentage change in odds was -1.8% (95% confidence interval (CI) -2.8% to -0.8%). However, there was no evidence of a trend in the prevalence of history of diagnosed CHD (annual change in odds 0.1%, 95% CI -1.0% to 1.2%). Over the same period, the CHD mortality rate fell substantially (annual change -4.1%, 95% CI -6.5% to -1.6%); rates of non-fatal myocardial infarction, all major CHD events, and first major CHD event fell by -1.7% (95% CI -3.9% to 0.5%), -2.5% (95% CI -4.1% to -0.8%), and -2.4% (95% CI% -4.3 to -0.4%), respectively. CONCLUSIONS: These results suggest that middle aged British men are less likely to experience symptoms of angina than in previous decades but are just as likely to have a history of diagnosed CHD. Despite falling rates of new major events and falling symptom prevalence, the need for secondary prevention among middle aged men with established CHD is as great as ever.

Adult↗

The use of numbers needed to treat derived from systematic reviews and meta-analysis. Caveats and pitfalls.

Numbers needed to treat (NNTs) may be used to present the effects of treatment and are the reciprocal of the absolute difference between treatment and control groups in a randomized controlled trial. NNTs are sensitive to factors that change the baseline risk of trial participants: the outcome considered; characteristics of patients; secular trends in incidence and case-fatality; and clinical setting. NNTs derived from pooled absolute risk differences in meta-analyses are commonly presented and easily calculated by meta-analytic software but may be seriously misleading because of heterogeneity between trials included in meta-analyses. Meaningful NNTs are obtained by applying the pooled relative risk reductions calculated from meta-analyses or individual trials to the baseline risk relevant to specific patient groups. This process will give a range of NNTs depending on whether patients are at high, low, or intermediate levels of risk, rather than a potentially misleading single number.

Clinical Trials as Topic↗

Cross-cultural validation of the London Handicap Scale in Hong Kong Chinese.

STUDY OBJECTIVE: To investigate the cross-cultural validity of London Handicap Scale in Hong Kong Chinese. DESIGN: Ratings of the utility of 10 hypothetical health scenarios were given by groups of HK Chinese subjects. Measured scores were compared with calculated scores from published scale weights of London Handicap Scale, which were based on utility ratings made by UK subjects. SETTING: A rehabilitation hospital in Hong Kong. SUBJECTS: A total of 164 HK Chinese, comprising doctors, medical students, nonmedical hospital staff, geriatric day hospital stroke and nonstroke patients, community day-care centre elderly, old age hostel elderly, young disabled inpatients and young community-dwelling disabled citizens. MAIN RESULTS: There was a close correlation between the mean scores of HK subjects and the calculated scores derived from the published UK scale weights, apart from one scenario (Pearson's correlation coefficient r = 0.87 p = 0.001). The correlations were high for all subgroups, between which there was good consensus. Measured utilities were significantly different between subgroups for only one scenario. For this scenario of moderate to severe handicap in mobility, physical dependence, occupation and social integration, but with excellent orientation and economic self sufficiency: (1) older age groups gave better scores than younger age groups (p < 0.0005); (2) subjects with poor subjective health status gave better scores than those with good subjective health status (p = 0.002); (3) subjects related to the medical or hospital field, i.e. doctors, medical students and nonmedical hospital staff, gave worse scores than other subject groups (p < 0.0005). CONCLUSION: The concept of handicap applies across cultures. Perception of severity of selected real life handicap scenarios by HK Chinese were well estimated using scale weights from UK populations developed for the London Handicap Scale. Significant differences in perception of certain handicap scenarios by different population subgroups deserve further study.

Activities of Daily Living↗