Lancet
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Randomized Controlled Trial Multicenter Study Clinical Trial
Gastric intramucosal pH as a therapeutic index of tissue oxygenation in critically ill patients.
Falls in gastric intramucosal pH (pHi) are associated with morbidity and mortality in patients admitted to intensive-care units (ICU). We tested the hypothesis that ICU outcome can be improved by therapy guided by changes in pHi and aimed at improving systemic oxygen availability. We studied 260 patients admitted to ICUs with APACHE II scores of 15-25. ⋯ There were no significant differences between protocol and control groups in demographic characteristics, admission blood gases or haemoglobin concentration, number or type of organ system failures, or the intensity of ICU care. For patients admitted with low pHi, survival was similar in the protocol and control groups (37% vs 36%), whereas for those admitted with normal pHi, survival was significantly greater in the protocol than in the control group (58% vs 42%; p less than 0.01). Therapy guided by pHi measurements improved survival in patients whose pHi on admission to ICU was normal. pHi-guided resuscitation may help improve outcome in such patients by preventing splanchnic organ hypoxia and the development of a systemic oxygen deficit.
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Randomized Controlled Trial Multicenter Study Comparative Study Clinical Trial
Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group.
A randomised double-blind prevention trial with a factorial design was conducted at 33 centres in seven countries to determine whether supplementation with folic acid (one of the vitamins in the B group) or a mixture of seven other vitamins (A,D,B1,B2,B6,C and nicotinamide) around the time of conception can prevent neural tube defects (anencephaly, spina bifida, encephalocele). A total of 1817 women at high risk of having a pregnancy with a neural tube defect, because of a previous affected pregnancy, were allocated at random to one of four groups--namely, folic acid, other vitamins, both, or neither. 1195 had a completed pregnancy in which the fetus or infant was known to have or not have a neural tube defect; 27 of these had a known neural tube defect, 6 in the folic acid groups and 21 in the two other groups, a 72% protective effect (relative risk 0.28, 95% confidence interval 0.12-0.71). ⋯ There was no demonstrable harm from the folic acid supplementation, though the ability of the study to detect rare or slight adverse effects was limited. Folic acid supplementation starting before pregnancy can now be firmly recommended for all women who have had an affected pregnancy, and public health measures should be taken to ensure that the diet of all women who may bear children contains an adequate amount of folic acid.
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Randomized Controlled Trial Multicenter Study Clinical Trial
MRC European Carotid Surgery Trial: interim results for symptomatic patients with severe (70-99%) or with mild (0-29%) carotid stenosis. European Carotid Surgery Trialists' Collaborative Group.
The European Carotid Surgery Trial is a multicentre trial of carotid endarterectomy for patients who, after a carotid territory non-disabling ischaemic stroke, transient ischaemic attack, or retinal infarct, are found to have a stenotic lesion in the relevant (ipsilateral) carotid artery. Over the past 10 years 2518 patients have been randomised, and the mean follow-up is now almost 3 years among the 2200 thus far available for analysis of the incidence of strokes that lasted more than 7 days. For the patients with "moderate" (30-69%) stenosis on their prerandomisation angiogram the balance of surgical risk and eventual benefit remains uncertain, and full recruitment continues. ⋯ For 778 patients with "severe" (70-99%) stenosis, however, the risks of surgery were significantly outweighed by the later benefits: although 7.5% had a stroke (or died) within 30 days of surgery, during the next 3 years the risks of ipsilateral ischaemic stroke were (by life-table analysis) an extra 2.8% for surgery-allocated and 16.8% for control patients (a sixfold reduction, p less than 0.0001). There was also a small reduction in other strokes, and at 3 years the total risk of surgical death, surgical stroke, ipsilateral ischaemic stroke, or any other stroke was 12.3% for surgery and 21.9% for control (difference 9.6% SD 3.3, 2p less than 0.01). The main concern was to avoid disabling or fatal events, and, among severe stenosis patients, 3.7% had a disabling stroke (or died) within 30 days of surgery, an extra 1.1% surgery versus 8.4% control (p less than 0.0001) had a disabling or fatal ipsilateral ischaemic stroke by 3 years, and the total 3-year risk of any disabling or fatal stroke (or surgical death) was 6.0% surgery versus 11.0% control (overall difference 5.0% SD 2.3, 2p less than 0.05); but, for disabling or fatal stroke the control risks seemed to diminish after the first year, so delay of surgery by just a few months after clinical presentation might make this overall difference non-significant.
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Randomized Controlled Trial Multicenter Study Comparative Study Clinical Trial
GISSI-2: a factorial randomised trial of alteplase versus streptokinase and heparin versus no heparin among 12,490 patients with acute myocardial infarction. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico.
A multicentre, randomised, open trial with a 2 x 2 factorial design was conducted to compare the benefits and risks of two thrombolytic agents, streptokinase (SK, 1.5 MU infused intravenously over 30-60 min) and alteplase (tPA, 100 mg infused intravenously over 3 h) in patients with acute myocardial infarction admitted to coronary care units within 6 h from onset of symptoms. The patients were also randomised to receive heparin (12,500 U subcutaneously twice daily until discharge from hospital, starting 12 h after beginning the tPA or SK infusion) or usual therapy. All patients without specific contraindications were given atenolol (5-10 mg iv) and aspirin (300-325 mg a day). ⋯ The incidence of major bleeds was significantly higher in SK and heparin treated patients (respectively, tPA 0.5%, SK 1.0%, RR 0.57, 95% Cl 0.38-0.85; hep 1.0%, no hep 0.6%, RR 1.64, 95% Cl 1.09-2.45), whereas the overall incidence of stroke was similar in all groups. SK and tPA appear equally effective and safe for use in routine conditions of care, in all infarct patients who have no contraindications, with or without post-thrombolytic heparin treatment. The 8.8% hospital mortality of the study population (compared with approximately 13% in the control cohort of the GISSI-1 trial) indicates the beneficial impact of the proven acute treatments for AMI.
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Multicenter Study Comparative Study Clinical Trial
Blood pressure, stroke, and coronary heart disease. Part 1, Prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias.
The associations of diastolic blood pressure (DBP) with stroke and with coronary heart disease (CHD) were investigated in nine major prospective observational studies: total 420,000 individuals, 843 strokes, and 4856 CHD events, 6-25 (mean 10) years of follow-up. The combined results demonstrate positive, continuous, and apparently independent associations, with no significant heterogeneity of effect among different studies. Within the range of DBP studied (about 70-110 mm Hg), there was no evidence of any "threshold" below which lower levels of DBP were not associated with lower risks of stroke and of CHD. ⋯ But, because of the diluting effects of random fluctuations in DBP, these substantially underestimate the true associations of the usual DBP (ie, an individual's long-term average DBP) with disease. After correction for this "regression dilution" bias, prolonged differences in usual DBP of 5, 7.5, and 10 mm Hg were respectively associated with at least 34%, 46%, and 56% less stroke and at least 21%, 29%, and 37% less CHD. These associations are about 60% greater than in previous uncorrected analyses. (This regression dilution bias is quite general, so analogous corrections to the relations of cholesterol to CHD or of various other risk factors to CHD or to other diseases would likewise increase their estimated strengths.) The DBP results suggest that for the large majority of individuals, whether conventionally "hypertensive" or "normotensive", a lower blood pressure should eventually confer a lower risk of vascular disease.