Treatment of atopic eczema in children: clinical trial of 10% sodium cromoglycate ointment.

In a double-blind randomised group-comparative trial 21 children with chronic atopic eczema were treated twice daily for up to 12 weeks with an ointment containing 10% sodium cromoglycate (SCG) in white soft paraffin. A similar group of 21 children was treated for up to 12 weeks with a placebo ointment consisting of the white soft-paraffin base only. The number of patients who withdrew from the trial because treatment was ineffective was significantly greater in the placebo group (16) than in the SCG group (four). Comparison between the two groups also showed significant improvement in inflammation, lichenification, and cracking and the symptoms of itching and sleep disturbance among those on SCG treatment. At the end of treatment significantly more patients in the SCG group (16) had benefited from treatment compared with only two patients in the placebo group. No patients experienced side effects. I conclude that SCG ointment may be a safe alternative to topical steroids in the treatment of atopic eczema in children.     

Reduction in mortality after myocardial infarction with long-term beta-adrenoceptor blockade. Multicentre international study: supplementary report.

In a controlled multicentre trial carried out to assess the value of long-term practolol treatment after myocardial infarction the provisional results showed a significant reduction in mortality, though some of the data were lacking. These have now been included and the results updated. The final figures for all deaths were 78 in the placebo group of 1533 patients and 48 in the practolol group of 1520 patients. The reduction in mortality (38%) was significant at the 1% level. The figures for non-fatal reinfarction (97 in the placebo group, and 75 in the practolol group) were not significantly different. Patients with pre-entry anterior infarction, and especially those with a diastolic blood pressure equal to or below the mean (78 mm Hg) at entry to the trial, were at high risk but benefited particularly well from beta-adrenoceptor blockade. After pre-entry inferior infarction the percentage reduction in deaths occurring within two hours after symptoms of a new event was similar to that after anterior infarction, but the incidence of death more than two hours after the event was greater in the practolol-treated group. Thus the difference between groups in total deaths after pretrial inferior infarction was marginal. Until the results of further trials are reported long-term beta-adrenoceptor blockade (possibly up to two years) is recommended after uncomplicated anterior myocardial infarction.     

Trial of an Anti-inflammatory Agent (Indomethacin) in Low Back Pain with and without Radicular Involvement

A short-term double-blind sequential trial of indomethacin against placebo in the treatment of low back pain, with and without nerve root pain such as sciatica, showed that indomethacin was significantly more effective than placebo in the group with nerve root pain. On the other hand, no difference was found between the treatments in the patients with uncomplicated low back pain. This difference may result from an effect of indomethacin on the inflammatory process around the nerve root which has been shown to be present when this is compressed.     

Persistent Behaviour and Electroencephalographic Changes after Single Doses of Nitrazepam and Amylobarbitone Sodium

In a double-blind cross-over trial the effects of nitrazepam (5 and 10 mg.), amylobarbitone sodium (100 and 200 mg.), and placebo were compared in normal healthy young people. Though they reported a good night''s sleep and adjudged themselves to be alert after all four drug treatments, behavioural tests showed their performance to be significantly impaired 13 hours after treatment with nitrazepam or amylobarbitone, and E.E.G. records showed more drowsiness and light sleep 18 hours after treatment with nitrazepam than with amylobarbitone or placebo. E.E.G. fast activity was more plentiful after drugs in either dosage than with placebo.     

Combined oral and nasal beclomethasone diproprionate in children with atopic eczema: a randomised controlled trial.

In a double blind, placebo controlled, crossover trial in 26 children with severe atopic eczema those receiving four weeks'' treatment with combined oral plus nasal beclomethasone diproprionate improved significantly more than those receiving placebo. No adverse effects were observed, but 24 hour urinary cortisol excretion was slightly reduced. This combination may provide effective treatment in refractory atopic eczema with relatively little of the danger associated with systemic administration of prednisolone and other traditional corticosteroids.     

Baclofen in the Treatment of Spasticity

Baclofen† (Lioresal), a derivative of gamma-aminobutyric acid, was introduced in 1966 as a possible treatment for spasticity due to corticospinal tract lesions. Preliminary studies suggested that it may be more effective than other spasmolytic agents currently available, and a double-blind controlled trial in a group of 23 patients against placebo has shown it to be significantly more effective.     

Effect of nadolol on plasma lipids in hyperthyroidism

The effect of Nadolol treatment on lipid subfractions in a group of 23 hyperthyroid patients was assessed in a randomised double-blind placebo controlled trial lasting six weeks, carbimazole being given to both groups from weeks 2 to 6. Clinical and biochemical euthyroidism was seen in both groups at 6 weeks; no effect of nadolol on peripheral monodeiodination of T4 to T3 was observed. At time 0 there were significant negative correlations between total cholesterol and free T3 (r = 0.68), and free T4 (r = 0.54). In the Nadolol group there were significant rises between 0 and 6 weeks in total cholesterol (52.6%, P less than 0.01), LDL cholesterol (30.3%, P less than 0.01) and HDL cholesterol (18.2%, P less than 0.05). HDL cholesterol rose significantly in the placebo group (12.4%, P less than 0.05) but there were no significant increases in LDL cholesterol or total cholesterol. The rise in triglyceride during this period in the Nadolol group (64.7%, P less than 0.05) was significantly greater (P less than 0.05) than the rise in the placebo group (8.8%). Nadolol increases triglyceride more than placebo during the early management of hyperthyroidism.     

Induction of remissions of insulin-dependent diabetes by cyclosporin

The effect of cyclosporine was evaluated in a double blind placebo controlled trial in 122 recent onset insulin-dependent diabetics. A significantly higher incidence of complete remissions was observed in patients treated with cyclosporine than in those receiving placebo (respectively 24 and 5.8%). The effect was still more clear-cut in patients having presented the highest cyclosporine blood level (37%). These results which have been obtained with modest toxicity demonstrate that cyclosporine induces remission of insulin-dependent diabetes and prompt to set up new controlled trials to evaluate the duration of the effect obtained and the potential risks of the treatment.     

Sulpiride improves inadequate lactation.

Twenty-eight newly delivered mothers with inadequate lactation volunteered for a placebo-controlled double-blind trial of sulpiride 50 mg thrice daily for four weeks. Treatment was allocated at random, and serum prolactin concentrations and breast-milk yields were measured before and serially during the trial. Of the 26 women who completed the trial, 14 had taken sulpiride and 12 the placebo. In the sulpiride-treatment group the mean maternal serum prolactin concentration rose from 49.0 +/- SE 3.6 micrograms/l to a maximum of 402.1 +/0 43.2 micrograms/l at two weeks; in the placebo-treated group, however, the concentration fell during the trial (from 84.7 +/- 24.0 micrograms/l to 47.8 +/- 8.6 micrograms/l). Mean breast-milk yields also increased in the sulpiride-treatment group (by an average of 212-265 ml) and fell in the women given placebo. Of the 14 infants in the sulpiride-treatment group, four did not need supplementary feeds during the trial; in the control group, however, all infants continued to require such feeds. Infants in the sulpiride-treatment group gained significantly more weight than did the controls (p less than 0.05). Three women taking sulpiride complained of mild side effects, but none occurred in the infants. These findings suggest that sulpiride is an effective treatment for inadequate lactation in the puerperium.     

Clinical Trial of Emepronium Bromide in Nocturnal Frequency of Old Age

A double-blind cross-over trial of emepronium bromide (Cetiprin) in nocturnal frequency of micturition in a group of elderly women living in their homes showed that the drug was superior to placebo in diminishing urinary frequency, though not every person benefited. It is suggested that the drug may alter the established habit of rising at night to pass urine. Side-effects were negligible.     

Effect on intra-arterial blood pressure of slow release metoprolol combined with placebo or chlorthalidone.

Thirty patients with essential hypertension participated in a double blind crossover trial in which they were randomly allocated to treatment with either once daily slow release metoprolol (200 mg) with placebo or once daily slow release metoprolol (200 mg) with chlorthalidone (25 mg). Ambulatory intra-arterial blood pressure was recorded continuously for 24-48 hours before treatment and two months after each change in regimen. The response of blood pressure and pulse rate to a standard exercise protocol that included supine rest and tilt, isometric, and dynamic bicycle exercise was measured during the same recording periods. Both treatments appreciably reduced blood pressure and pulse rate; mean daytime intra-arterial blood pressure was reduced from 174/95 mm Hg to 158/85 mm Hg by metoprolol plus placebo and to 143/78 mm Hg by metoprolol plus chlorthalidone. This reduction with the combined treatment was significantly greater than with metoprolol and placebo (p systolic = 0.001, p diastolic = 0.004). Mean night time pressures were reduced from 148/78 mm Hg to 139/75 mm Hg by metoprolol plus placebo and to 116/61 mm Hg by metoprolol plus chlorthalidone. Again the reduction in blood pressure was significantly greater with combined treatment (p less than 0.001) than with metoprolol plus placebo. Once daily slow release metoprolol is effective in controlling blood pressure, but this effect is greatly enhanced by the addition of a diuretic.     

Efficacy of ketoprofen in treating primary dysmenorrhea.

A 6-month double-blind crossover trial compared ketoprofen with placebo in the treatment of primary dysmenorrhea in 27 women who satisfied explicit inclusion and exclusion criteria. The response to treatment was assessed with a pain scale and a disability scale and by noting amelioration of associated symptoms, such as nausea, vomiting, diarrhea, fatigue, dizziness and headache. Ketoprofen was significantly superior to placebo in relieving the pain (p less than 0.001), disability (p less than 0.001) and headache (p less than 0.01) associated with menstruation. No order effect of treatment was observed. Adverse effects were few and minimal.     

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,double blind,placebo controlled trial of penicillin V and amoxycillin in treatment of acute sinus infections in adults.

OBJECTIVES--To compare the effectiveness of penicillin V and amoxycillin with placebo in treatment of adult patients with acute sinusitis. DESIGN--Randomised, double blind, placebo controlled trial. SETTING--Norwegian general practice. SUBJECTS--130 adult patients with a clinical diagnosis of acute sinusitis confirmed by computed tomography. MAIN OUTCOME MEASURES--Subjective status after three and 10 days of treatment, difference in clinical severity score between day 0 and day 10 as evaluated by the general practitioner, difference in score from computed tomography on day 0 and day 10, and duration of sinusitis. RESULTS--Amoxycillin and penicillin V led to significantly faster and better recovery than placebo. By day 10, 71 patients receiving antibiotic treatment- (86%) considered themselves to be recovered or much better compared with 25 (57%) receiving placebo. The mean (95% confidence interval) reductions in clinical severity scores by day 10 were 5.4 (5.0 to 5.8) for penicillin V, 5.5 (4.9 to 6.0 for amoxycillin, and 3.4 (2.8 to 4.0) for placebo. For the antibiotic groups combined the number of patients with the greatest degree of improvement on computed tomography (scale 0-16)-that is, score 5-16 on day 10-was 31/83 (37%) compared with 10/44 (23%) receiving placebo. The median duration of the sinusitis was nine days in the amoxycillin group, 11 days in the penicillin V group, and 17 days in the placebo group. CONCLUSION--Penicillin V and amoxycillin are significantly more effective than placebo in the treatment of acute sinusitis.     

Fluoxetine and suicide: a meta-analysis of controlled trials of treatment for depression.

OBJECTIVE--A comprehensive meta-analysis of clinical trial data was performed to assess the possible association of fluoxetine and suicidality (suicidal acts and ideation). DESIGN--Retrospective analysis of pooled data from 17 double blind clinical trials in patients with major depressive disorder comparing fluoxetine (n = 1765) with a tricyclic antidepressant (n = 731) or placebo (n = 569), or both. MAIN OUTCOME MEASURES--Multiple data sources were searched to identify patients with suicidal acts. Suicidal ideation was assessed with item 3 of the Hamilton depression rating scale, which systematically rates suicidality. Emergence of substantial suicidal ideation was defined as a change in the rating of this item from 0 or 1 at baseline to 3 or 4 during double blind treatment; worsening was defined as any increase from baseline; improvement was defined as a decrease from baseline at the last visit during the treatment. RESULTS--Suicidal acts did not differ significantly in comparisons of fluoxetine with placebo (0.2% v 0.2%, p = 0.494, Mantel-Haenszel adjusted incidence difference) and with tricyclic antidepressants (0.7% v 0.4%, p = 0.419). The pooled incidence of suicidal acts was 0.3% for fluoxetine, 0.2% for placebo, and 0.4% for tricyclic antidepressants, and fluoxetine did not differ significantly from either placebo (p = 0.533, Pearson''s chi 2) or tricyclic antidepressants (p = 0.789). Suicidal ideation emerged marginally significantly less often with fluoxetine than with placebo (0.9% v 2.6%, p = 0.094) and numerically less often than with tricyclic antidepressants (1.7% v 3.6%, p = 0.102). The pooled incidence of emergence of substantial suicidal ideation was 1.2% for fluoxetine, 2.6% for placebo, and 3.6% for tricyclic antidepressants. The incidence was significantly lower with fluoxetine than with placebo (p = 0.042) and tricyclic antidepressants (p = 0.001). Any degree of worsening of suicidal ideation was similar with fluoxetine and placebo (15.4% v 17.9%, p = 0.196) and with fluoxetine and tricyclic antidepressants (15.6% v 16.3%, p = 0.793). The pooled incidence of worsening of suicidal ideation was 15.3% for fluoxetine, 17.9% for placebo, and 16.3% for tricyclic antidepressants. The incidence did not differ significantly with fluoxetine and placebo (p = 0.141) or tricyclic antidepressants (p = 0.542). Suicidal ideation improved significantly more with fluoxetine than with placebo (72.0% v 54.8%, p less than 0.001) and was similar to the improvement with tricyclic antidepressants (72.5% v 69.8%, p = 0.294). The pooled incidence of improvement of suicidal ideation was 72.2% for fluoxetine, 54.8% for placebo, and 69.8% for tricyclic antidepressants. The incidence with fluoxetine was significantly greater than with placebo (p less than 0.001) and did not differ from that with tricyclic antidepressants (p = 0.296). CONCLUSIONS--Data from these trials do not show that fluoxetine is associated with an increased risk of suicidal acts or emergence of substantial suicidal thoughts among depressed patients.     

Outpatient Maintenance of Chronic Schizophrenic Patients with Long-acting Fluphenazine: Double-blind Placebo

A double-blind placebo trial of fluphenazine decanoate, a long-acting phenothiazine, was carried out to determine its value in maintenance therapy of chronic schizophrenic outpatients already established on the drug for a minimum period of eight weeks. In low doses it was significantly more effective than placebo in preventing relapse and admission to hospital. Relapse was accompanied by a resurgence of specifically schizophrenic symptoms and by an increase in abnormalities described by the relatives. There was no difference between the experimental and control groups in the treatment required for depression. The group on active medication required more treatment for Parkinsonism, but this difference did not reach statistical significance.In the context of a well-run special clinic for outpatient follow-up of chronic schizophrenic patients these results confirm the usefulness of long-acting fluphenazine. By inference, the benefit of this treatment highlights the need for adequate community services to deal with the residual chronic disabilities which are characteristic of these patients.     

Effectiveness and tolerance of selected Polish antacids in the therapy of duodenal ulcer disease. A placebo- and ranitidine-controlled study

In a randomized, open clinical trial we compared the efficiency of selected Polish antacids Alugastrin, Gastrin and Wikalina with ranitidine and placebo in the healing of duodenal ulcer, pain relief and drug toleration. One hundred and ten outpatients completed the study. The trial showed that antacids and ranitidine had similar rates of duodenal ulcer healing which were significantly better than placebo. After 4 weeks of treatment with Alugastrin, Gastrin, Wikalina and ranitidine the healing rates were 70%, 76%, 71% and 81%, respectively, compared to placebo 44%. Efficiency of antacids in pain relief was similar to placebo and slightly lower than ranitidine. Antacids were well tolerated, except for hypermagnezemia and urine alkalization caused by Gastrin and Wikalina. We conclude that studied antacids are as effective as ranitidine in promoting healing of duodenal ulcer, but because of side effects they are not recommended for maintenance therapy.     

Treating hypertension in black compared with white non-insulin dependent diabetics: a double blind trial of verapamil and metoprolol.

STUDY OBJECTIVE--To compare responses of blood pressure to the calcium antagonist verapamil and the beta blocker metoprolol in black compared with white diabetics with hypertension and to monitor urinary albumin excretion in relation to fall in blood pressure. DESIGN--Double blind, placebo controlled, random order crossover trial with four week placebo run in period and two six week active phases separated by a two week placebo washout period. SETTING--Outpatient department of a general hospital in a multiethnic health department. Patients--Diabetic patients with hypertension. Four dropped out before randomisation; 25 black and 14 white patients completed the trial. INTERVENTIONS--Patients given slow release verapamil 120 mg or 240 mg twice daily with placebo or metoprolol 50 mg or 100 mg twice daily with placebo. Treatment for diabetes (diet alone or with oral hypoglycaemic drugs) remained unchanged. END POINT--Comparison of changes in blood pressure in the two groups taking both drugs. MEASUREMENTS AND MAIN RESULTS--Metoprolol had little effect on blood pressure in black patients (mean fall 4.0 mm Hg systolic (95% confidence interval -2.5 to 10.4 mm Hg), 4.3 mm Hg diastolic (-0.8 to 9.5)) but more effect in white patients (mean falls 13.4 mm Hg (0.1 to 26.7) and 10.6 mm Hg (4.5 to 16.7) respectively). Verapamil was more effective in both groups, with mean falls of 8.8 mm Hg (2.4 to 15.0) and 8.1 mm Hg (5.0 to 11.2) in black patients and 19.1 mm Hg (5.4 to 32.9) and 11.4 mm Hg (0.9 to 22.0) in white patients. Heart fate fell significantly in black patients taking metoprolol, which suggested compliance with treatment. Metabolic variables were unaltered by either treatment. Plasma renin activity was low in both groups after metoprolol treatment, but change in blood pressure could not be predicted from baseline plasma renin activity. Urinary albumin:creatinine ratio was independently related to baseline blood pressure but not significantly changed by treatment. CONCLUSIONS--beta Blockers alone are not effective in treating hypertension in black diabetics. Verapamil is effective but less so than in white patients. As yet no ideal monotherapy exists for hypertension in black patients.     

Long term propranolol treatment and changes in body weight after myocardial infarction.

OBJECTIVE--To determine the effect of long term propranolol treatment on body weight. DESIGN--Retrospective analysis of data from a placebo controlled randomised double blind clinical trial (the beta blocker heart attack trial). PATIENTS--3837 Men and women randomised 5-21 days after an acute myocardial infarction to treatment with placebo or propranolol for up to 40 months. Patients were followed up at annual visits. MAIN OUTCOME MEASURE--Changes in body weight. RESULTS--At the first annual visit patients treated with propranolol had gained more weight than those given placebo (mean weight gain 2.3 kg v 1.2 kg respectively, mean difference 1.2 kg (95% confidence interval 0.9 to 1.5]. These group differences remained at the second and third annual visits. The difference in weight gain could not be explained by discrepancies in the use of diuretics or in physical activity and was similar in patients of both sexes and of all ages. CONCLUSION--Long term beta blockade results in a sustained weight gain.     

Effect of ergotamine on plasma metabolite and insulin-like growth factor-1 concentrations in cows

Bovine plasma was assayed to determine if ergotamine affected plasma metabolite and insulin-like growth factor-1 (IGF-1) concentrations. In Experiment 1, four cows received a single bolus intravenous injection of ergotamine tartrate (19 microg/kg body wt.) or saline vehicle in a crossover design 2 days after prostaglandin-induced luteolysis. Treatmentxtime affected plasma glucose, triglyceride, total cholesterol and IGF-1 concentrations. Glucose and cholesterol were increased after ergotamine. Triglycerides were elevated within 1 h after ergotamine, but were decreased 3 h after ergotamine treatment. Plasma IGF-1 decreased in response to ergotamine. Blood constituents were unchanged after treatment with saline. In Experiment 2, six cows received a single bolus intravenous injection of ergotamine (20 microg/kg body wt.) or saline vehicle in a crossover design 10 days after receiving norgestomet (6 mg) via subcutaneous ear implant. Treatmentxtime affected glucose, triglycerides, total cholesterol and IGF-1 concentrations. Glucose and cholesterol were increased after ergotamine. Triglycerides were elevated 1 h after ergotamine and decreased 3-7 h after ergotamine. Plasma IGF-1 decreased after ergotamine treatment. Blood constituents were unresponsive to the saline vehicle. Results indicated ergotamine altered plasma metabolite and IGF-1 concentrations in cows.