Controlled trial of azathioprine in chronic ulcerative colitis.

A double-blind controlled trial of azathioprine in a dose of 2-2.5 mg/kg body weight over six months was conducted among 44 patients with active chronic ulcerative colitis. Three patients treated with placebo did not complete the trial because their disease became so severe that colectomy was performed. Among patients who completed the trial the mean dose of prednisolone necessary to control the disease decreased in those treated with azathioprine and those treated with placebo; the reduction was greater among those who took azathioprine (p less than 0.001). Activity of the disease apparently improved in both treatment groups but a significant (p less than 0.001) trend was observed only in those patients treated with azathioprine. No serious side effects from azathioprine occurred during the trial but seven of 24 patients had to stop the drug because of nausea. Azathioprine may have a role in the treatment of a few patients wih troublesome chronic colitis for whom conventional drug treatment is ineffectual, or for whom continuous systemic corticosteroid treatment is needed to control symptoms, and for whom surgical treatment is inappropriate.     

Randomised controlled trial of vancomycin for pseudomembranous colitis and postoperative diarrhoea.

The efficacy of vancomycin in pseudomembranous colitis was assessed in a prospective randomised controlled trial. Forty-four patients with postoperative diarrhoea were allocated to five days'' treatment with either 125 mg vancomycin six-hourly or a placebo. Sixteen patients had high titres of the neutralised faecal toxin characteristic of pseudomembranous colitis; nine received vancomycin and seven placebo. At the end of treatment faecal toxins were present in one patient given vancomycin compared with five of the controls. Vancomycin caused the disappearance of Clostridum difficile from the stool in all except one patient, whereas toxicogenic strains of Cl difficile persisted in all but one of the controls. Histological evidence of psuedomembranous colitis had disappeared by the end of treatment in six out of seven patients given vancomycin compared with only one out of seven patients given vancomycin compared with only one out of five patients given placebo. In patients with faecal toxins bowel habit had returned to normal in seven of the vancomycin group compared with only one of the controls, but there was no significant difference in clinical response among patients without faecaal toxins. The results suggest that vancomycin eliminates toxin-producing Cl difficile from the colon and is associated with rapid clinical and histological improvement in patients with pseudomembranous colitis.     

Randomised controlled trial of nicotine chewing-gum.

The effectiveness of 2 mg nicotine chewing-gum as an aid to stopping smoking was compared with a placebo containing 1 mg nicotine, but unbuffered, in a double-blind randomised trial. Of 58 subjects given the active gum, 27 (47%) were not smoking at one-year follow-up compared with 12 (21%) of the 58 subjects treated with placebo (p less than 0.025). By the most stringent criterion of outcome, 18 (31%) subjects in the active treatment group and eight (14%) in the placebo group had not smoked at all from the start of treatment to follow-up at one year (p less than 0.05). Subjects receiving the active gum experienced less severe withdrawal symptoms and rated their gum as more helpful than did the placebo group. Minor side effects were common but only gastric symptoms were more frequent with the active gum. Subjects receiving active gum used it for longer than those receiving placebo but most stopped using it within six months and only four (7%) developed longer-term dependence. The number of gums used daily correlated significantly with pretreatment blood nicotine concentrations in the active treatment group and with pretreatment cigarette consumption in the placebo group. A lower pretreatment blood nicotine value was the best predictor of success at one year (p less than 0.001) but there was no significant relation to cigarette consumption, sex, and social class. The results clearly confirm the usefulness of nicotine chewing-gum as an aid to stopping smoking and imply a definite role for nicotine in cigarette dependence and withdrawal. Successful use of the gum requires careful attention to subjects'' expectations and clear instructions on how to use it.     

Randomised controlled trial of computer-held medical records in hypertensive patients.

A total of 278 hypertensive patients in three clinics were randomly allocated to have their medical records held in a computer system (136) or on standard hospital notes (142). For the computer system the doctor completed a structured input form, and the information on symptoms, physical findings, and diagnoses was more complete than that in the standard notes. This resulted in certain symptoms and risk factors being recognised more often when the computer system was used. The hypertension clinics'' routines were not disrupted by the introduction of a computer-held system, and follow-up consultation times were not affected by the type of records kept, although the first consultation took eight minutes longer when computer documents were completed. The patients remained in the trial for one year and clinical management was assessed from blood pressure control, drop-out rates, and the frequency of performing investigations. These estimates of management showed no significant difference between the two groups, but the attempt to tailor the computer system to help management made the system acceptable to the doctors using it. The computer system continues to be used and is providing data for research into hypertension.     

Randomised controlled trial of intrapartum fetal heart rate monitoring.

OBJECTIVE--To compare effectiveness of different methods of monitoring intrapartum fetal heart rate. DESIGN--Prospective randomised controlled trial. SETTING--Referral maternity hospital, Harare, Zimbabwe. SUBJECTS--1255 women who were 37 weeks or more pregnant with singleton cephalic presentation and normal fetal heart rate before entry into study. INTERVENTIONS--Intermittent monitoring of fetal heart rate by electronic monitoring, Doppler ultrasound, use of Pinard stethoscope by a research midwife, or routine use of Pinard stethoscope by attending midwife. MAIN OUTCOME MEASURES--Abnormal fetal heart rate patterns, need for operative delivery for fetal distress, neonatal mortality, Apgar scores, admission to neonatal unit, neonatal seizures, and hypoxic ischaemic encephalopathy. RESULTS--Abnormalities in fetal heart rate were detected in 54% (172/318) of the electronic monitoring group, 32% (100/312) of the ultrasonography group, 15% (47/310) of the Pinard stethoscope group, and 9% (28/315) of the routine monitoring group. Caesarean sections were performed for 28% (89%), 24% (76), 10% (32), and 15% (46) of the four groups respectively. Neonatal outcome was best in the ultrasonography group: hypoxic ischaemic encephalopathy occurred in two, one, seven, and 10 cases in the four groups respectively; neonatal seizures occurred only in the last two groups (six and nine cases respectively); and deaths occurred in eight, two, five, and nine cases respectively. CONCLUSIONS--Abnormalities in fetal heart rate were more reliably detected by Doppler ultrasonography than with Pinard stethoscope, and its use resulted in good perinatal outcome. The use of relatively cheap ultrasound monitors should be further evaluated and promoted in obstetric units caring for high risk pregnancies in developing countries with scarce resources.     

Sulphasalazine retention enemas in ulcerative colitis: a double-blind trial.

Thirty-four patients with ulcerative colitis completed a double-blind assessment comparing the efficacy of two weeks of treatment with nightly retention enemas containing 3 g sulphasalazine or placebo. Symptom grading, sigmoidoscopic appearance, rectal biopsy specimens, and diary records were used to assess benefit and side effects. The active drug conferred significant benefit compared with placebo as shown by several criteria, but this benefit was confined to patients not already taking sulphasalazine by mouth. Overall assessment showed improvement in 11 of the 16 patients (70%) given the active treatment but in only two of the 18 (11%) given placebo. No side effects attributable to the drug were observed, even in patients previously intolerant to oral preparations. The logical therapeutic role of sulphasalazine enemas in ulcerative colitis would appear to be in patients who experience side effects such as nausea, abdominal discomfort, or headaches when taking the drug by mouth.     

Randomised controlled trial of day patient versus inpatient psychiatric treatment.

OBJECTIVE--To assess the proportion of acutely ill psychiatric patients who can be treated in a day hospital and compare the outcome of day patient and inpatient treatment. DESIGN--Prospective randomised controlled trial of day patient versus inpatient treatment after exclusion of patients precluded by severity of illness or other factors from being treated as day patients. All three groups assessed at three and 12 months. SETTING--Teaching hospital serving small socially deprived inner city area. Day hospital designed to take acute admissions because of few beds. PATIENTS--175 Patients were considered, of whom 73 could not be allocated. Of the remaining 102 patients, 51 were allocated to each treatment setting but only 89 became established in treatment--namely, 41 day patients and 48 inpatients. 73 Of these 89 patients were reassessed at three months and 70 at one year. INTERVENTIONS--Standard day patient and inpatient treatment. MAIN OUTCOME MEASURES--Discharge from hospital and return to previous level of social functioning; reduction of psychiatric symptoms, abnormal behaviour, and burden on relatives. RESULTS--33 Of 48 inpatients were discharged at three months compared with 17 of 41 day patients. But at one year 9 of 48 inpatients and three of 41 day patients were in hospital. 18 Of 35 day patients and 16 of 39 inpatients were at their previous level of social functioning at one year. The only significant difference at three months was a greater improvement in social role performance in the inpatients. At one year there was no significant difference between day patients and inpatients in present state examination summary scores and social role performance, burden, or behaviour. CONCLUSIONS--Roughly 40% of all acutely ill patients presenting for admission to a psychiatric unit may be treated satisfactorily in a well staffed day hospital. The outcome of treatment is similar to that of inpatient care but might possibly reduce readmissions. The hospital costs seem to be similar but further research is required to assess the costs in terms of extra demands on relatives, general practitioners, and other community resources.     

Randomised controlled trial of computer assisted management of hypertension in primary care.

The hypothesis that general practitioners would obtain better outcomes for patients with hypertension using a computer than doctors not using a computer was tested. Sixty family physicians were randomised to two treatment strategies. "Test" physicians completed a data collection form after each visit from a patient with hypertension and mailed the forms to the test centre for processing. Computer feedback on management was mailed to the doctors. This encouraged doctors to apply the "stepped care" protocol, supplied charts of diastolic blood pressure v time, and ranked patients'' diastolic blood pressures by percentile. Letters were mailed to patients to remind them of appointments. "Control" doctors filled out the same data collection forms as test physicians, but neither doctors nor patients received computer feedback. Physicians who used the computer saw more patients per practice than control doctors (test 50 patients, control 40). For all patients the length of follow up was significantly longer in test practices (test 199 days, control 167), and a smaller percentage dropped out of active treatment in test practices (test 37.5%, control 42.1%). For patients with "moderate" hypertension of a baseline diastolic pressure of greater than 104 mm Hg the mean score of the last recorded pressure was below the goal of 90 mm Hg in test practices (88.5 mm Hg), but it failed to reach this goal in control practices (93.3 mm Hg). A greater average reduction of diastolic pressure was achieved in test practices (test 21.7 mm Hg, control 16.7 mm Hg). Though patients with "moderate" hypertension were better controlled in test practices than in control practices, the patients in test practices visited their doctors less often (test 13.3 visits per patient-year, control 17.4 visits). Among patients with newly detected hypertension test practices achieved a greater reduction in diastolic pressure than control practices (test 15.1 mm Hg v control 11.3 mm Hg) and more sustained control of hypertension (test 323 days per patient-year with a diastolic pressure of 90 mm Hg or less v control 259 days).     

Randomised controlled trial of antibiotics in patients with cough and purulent sputum.

Two hundred and twelve adults with cough and purulent sputum of up to one week''s duration were allocated randomly to treatment with doxycycline or placebo capsules for up to 10 days. Cough, purulent sputum, feeling "off colour," and time off work lasted as long in treatment and control groups, but running nose persisted for a shorter time in the doxycycline group. The number of new episodes of lower respiratory tract infections, vaginal infections, gastrointestinal upsets, and otitis media over the next six months were the same in both groups, but fewer new upper respiratory infections were experienced by the doxycycline-treated patients. There is no consensus among doctors about using antibiotics in patients with cough and purulent sputum, and these results indicate that otherwise healthy people with these symptoms will usually get better without antibiotic treatment.     

Sulfasalazine-induced colitis complicating idiopathic ulcerative colitis.

A diagnosis of idiopathic ulcerative colitis was made in a previously healthy 9-year-old boy. Symptoms persisted despite therapy with sulfasalazine, 50 mg/kg daily, but they eventually responded to treatment with parenteral nutrition and prednisone, 40 mg daily. Metronidazole was also given to eradicate persistent Dientamoeba fragilis from the stools. The symptoms resolved over 3 weeks, and the daily dose of prednisone was tapered. On two subsequent occasions a challenge with sulfasalazine caused an immediate recurrence of loose, blood-streaked stools and of nonspecific histologic features of ulcerative colitis, which resolved when the sulfasalazine was discontinued.     

Randomised controlled trial of general practitioner intervention in patients with excessive alcohol consumption.

OBJECTIVE: To determine effectiveness of advice from general practitioners to heavy drinkers to reduce their excessive alcohol consumption (35 U or more a week for men, 21 U or more for women). DESIGN: Randomised, controlled double blind trial over 12 months with interim assessment at six months. SETTING: Group practices (n = 47; list size averaging 10,000) recruited from Medical Research Council''s general practice research framework, mostly in rural or small urban settings. PATIENTS: Patients recruited after questionnaire survey. Of total of 2571 (61.2%) of 4203 patients invited for interview who attended, 909 (35.4%) stated that in past seven days they had drunk above the limits set for study and had not received advice; they were randomised to control and treatment groups. INTERVENTIONS: Patients in treatment group were interviewed by general practitioner (who had had a training session) and received advice and information about how to reduce consumption and also given a drinking diary. END POINT: Study aimed at detecting a reduction in proportion of men with excessive alcohol consumption of 30% in treatment group and 20% in control group (for women 40% and 20%, respectively) with a power of 90% at 5% level of significance. In addition, corroborative measures such as estimation of gamma-glutamyltransferase activity were included. MEASUREMENTS AND MAIN RESULTS: At one year a mean reduction in consumption of alcohol of 18.2 (SE 1.5) U/week had occurred in treated men compared with a reduction of 8.1 (1.6) U/week in controls (p less than 0.001). The proportion of men with excessive consumption at interview had dropped by 43.7% in the treatment group compared with 25.5% in controls (p less than 0.001). A mean reduction in weekly consumption of 11.5 (1.6) U occurred in treated women compared with 6.3 (2.0) U in controls (p less than 0.05), with proportionate reductions of excessive drinkers in treatment and control groups of 47.7% and 29.2% respectively. Reduction in consumption increased significantly with number of general practitioner interventions. At one year the mean value for gamma-glutamyltransferase activity had dropped significantly more in treated men (-2.4 (0.9)IU/l) than in controls (+1.1(1.0)IU/l; t = 2.7, p less than 0.01). Reduction in gamma-glutamyltransferase activity tended to increase with number of intervention sessions in men. Changes in gamma-glutamyltransferase activity in women and changes in other indicators in both sexes did not differ significantly between treatment and control groups. CONCLUSIONS: If the results of this study were applied to the United Kingdom intervention by general practitioners could each year reduce to moderate levels the alcohol consumption of some 250000 men and 67500 women who currently drink to excess. General practitioners and other members of the primary health care team should therefore be encouraged to include counselling about alcohol consumption in their preventive activities.     

Randomised controlled trial of enalapril and beta blockers in non-diabetic chronic renal failure.

OBJECTIVE--To compare the ability of angiotensin converting enzyme inhibitors and beta blockers to slow the development of end stage renal failure in non-diabetic patients with chronic renal failure. DESIGN--Open randomised multicentre trial with three year follow up. SETTING--Outpatient departments of six French hospitals. PATIENTS--100 hypertensive patients with chronic renal failure (initial serum creatinine 200-400 mumol/l. 52 randomised to enalapril and 48 to beta blockers (conventional treatment). INTERVENTIONS--Enalapril or beta blocker was combined with frusemide and, if necessary, a calcium blocker or centrally acting drug in patients whose diastolic pressure remained above 90 mm Hg. RESULTS--17 patients receiving conventional treatment and 10 receiving enalapril developed end stage renal failure. The cumulative renal survival rate was significantly better in the enalapril group than in the conventional group (P < 0.05). The slope of the reciprocal serum creatinine concentration was steeper in the conventionally treated patients (-6.89 x 10(-5)l/mumol/month) than in the enalapril group (-4.17 x 10(-5)l/mumol/month; P < 0.05). No difference in blood pressure was found between groups. CONCLUSION--In hypertensive patients with chronic renal failure enalapril slows progression towards end stage renal failure compared with beta blockers. This effect was probably not mediated through controlling blood pressure.     

Oxygen radicals in ulcerative colitis.

This article reviews the pathophysiologic concept that superoxide and hydrogen peroxide, generated by activated leukocytes, together with low-molecular-weight chelate iron derived from fecal sources and from denatured hemoglobin, amplify the inflammatory response and subsequent mucosal damage in patients with active episodes of ulcerative colitis. The putative pathogenic mechanisms reviewed are as follows: (1) Dietary iron is concentrated in fecal material owing to normally limited iron absorption. (2) Mucosal bleeding, characteristic of ulcerative colitis, as well as supplemental oral iron therapy for chronic anemia, further conspire to maintain or elevate mucosal iron concentration in colitis. (3) Fenton chemistry, driven especially by leukocyte-generated superoxide and hydrogen peroxide, leads to formation of hydroxyl radicals. (4) The resultant oxidative stress leads to the extension and propagation of crypt abscesses, either through direct membrane disruption by lipid peroxidation or through generation of secondary toxic oxidants such as chloramines. (5) Chemotactic products of lipid peroxidation, including 4-hydroxynonenal, provide positive feedback to accelerate this inflammatory/oxidative process, leading to acute exacerbations of the disease. (6) Other oxidized products, such as oxidized tryptophan metabolites, created by free radical mechanisms in or near the mucosa, may act as carcinogens or tumor promotors that contribute to the exceedingly high incidence of colon carcinoma in patients suffering from chronic ulcerative colitis. In this way, self-sustaining cycles of oxidant formation may amplify flare-ups of inflammation and mucosal injury in ulcerative colitis. This concept, if proved correct by subsequent research, would provide a rationale for several novel clinical approaches to the management of ulcerative colitis, including use of SOD mimetics, iron chelators, and chain-breaking antioxidants.     

Olsalazine in active ulcerative colitis.

Olsalazine (azodisalicylate) is a new drug in which two molecules of 5-aminosalicylic acid are linked by an azo bond. Its role in the treatment of mildly active, distal ulcerative colitis was investigated. Sixty patients were randomly allocated to receive olsalazine 1 g or a placebo as a retention enema nightly for two weeks. Clinical improvement was seen in 19 (66%) and sigmoidoscopic improvement in 17 (59%) of the 29 patients receiving olsalazine compared with 12 (43%) and 11 (39%), respectively, of the 28 in the control group. These differences were not significant. In a second trial 40 patients were randomised to receive oral olsalazine 2 g daily or a placebo capsule for two weeks. Significant clinical and sigmoidoscopic improvement was seen in the patients receiving oral olsalazine compared with the patients receiving placebo capsules. Oral olsalazine may be valuable in the treatment of mildly active ulcerative colitis. Its role in maintaining remission is yet to be determined.