An open randomised trial was conducted to compare ceftazidime (120 mg/kg/day) with "conventional therapy" (chloramphenicol 100 mg/kg/day, doxycycline 4 mg/kg/day, trimethoprim 10 mg/kg/day, and sulphamethoxazole 50 mg/kg/day) in the treatment of severe melioidosis. A paired restricted sequential trial designed to detect a reduction in mortality from 80 to 40% in culture-positive patients surviving greater than 48 hours was stopped after 22 months. Of the 161 patients entered into the study, 65 had bacteriologically confirmed melioidosis and 54 of these were septicaemic. Ceftazidime treatment was associated with a 50% (95% CI 19-81%) lower overall mortality than conventional treatment (74% vs 37%; p = 0.009) and should now become the treatment of choice for severe melioidosis.

A randomised, controlled trial was carried out to determine whether suckling immediately after birth reduces the frequency of post-partum haemorrhage (PPH), the mean blood loss, and the frequency of retained placenta. The trial subjects were attended by traditional birth attendants (TBAs), and randomisation was by TBA and not by mother. 68 TBAs attended a course on third stage management and data collection; 19 had to be excluded from the trial. 23 TBAs in the early suckling group and 26 in the control group recorded blood loss in 2104 and 2123 deliveries of liveborn singletons, respectively. The frequency of PPH (loss greater than 500 ml) was 7.9% in the suckling group and 8.4% in the control group and the mean blood loss 258 ml and 256 ml, respectively. Neither of these results differed significantly between the groups. Analysis of the results by individual TBA showed no significant difference between the groups. The frequency of PPH in women of higher parity and in those with multiple pregnancies and stillbirths was high, as expected, which seems to validate the results. The frequency of retained placenta was too low to be analysed.

To test the hypothesis that non-steroidal anti-inflammatory drugs (NSAIDs) accelerate the progression of osteoarthritis by reducing synthesis of vasodilator prostaglandins, thereby diminishing joint perfusion, 105 osteoarthritis patients awaiting hip arthroplasty were treated prospectively with a strong or weak prostaglandin synthesis inhibitor, indomethacin or azapropazone, respectively. Pain and radiological joint space were monitored during the period up to arthroplasty and the condition of the excised femoral head was determined. As judged by radiological and histopathological data, the two treatment groups were at a similar pathophysiological end-point when they came to arthroplasty. In the indomethacin group the affected hips lost joint space more rapidly than did the contralateral hips, a difference not seen in the azapropazone group. The patients receiving azapropazone, who had higher concentrations of synovial vasodilator prostaglandins, took longer than the indomethacin group to reach the arthroplasty end-point. Potent inhibitors of prostaglandin synthesis may be inappropriate in the management of osteoarthritis of the hip.

The value of hyperbaric oxygen in the treatment of acute carbon monoxide intoxication was assessed in 629 adults who had been poisoned at home in the 12 h before admission to hospital. In patients without initial impairment of consciousness (group A) the effect of 6 h of normobaric oxygen (NBO) (group A0, n = 170) was compared with that of 2 h of hyperbaric oxygen (HBO) at 2 atmospheres absolute (ATA) plus 4 h NBO (group A1, n = 173). At the 1 month follow-up 66% of A0 and 68% of A1 patients had recovered. In patients with initial impairment of consciousness the effect of one session of HBO (group B1, n = 145) was compared with that of two sessions (group B2, n = 141); all group B patients also received 4 h of NBO. At 1 month of follow-up 54% group B1 and 52% group B2 patients had recovered. The 7 patients left with neuropsychiatric sequelae (3 B1, 4 B2) and the 4 who died (2 B1, 2 B2) had all presented with coma. HBO was not useful in patients who did not lose consciousness during carbon monoxide intoxication, irrespective of their carboxyhaemoglobin level, nor were two sessions of HBO in patients who sustained only a brief loss of consciousness. The prognosis is poorest for those presenting with coma; the trial needs to be pursued in this group of patients until the power of the study is sufficient to demonstrate the value or otherwise of HBO.

The routine recommendation to women to count fetal movements daily during late pregnancy for the prevention of antepartum late fetal death in normally formed singletons has been evaluated. 68,000 women were randomly allocated within thirty-three pairs of clusters either to a policy of routine counting or to standard care, which might involve selective use of formal counting or informal noting of movements. Antepartum death rates for normally formed singletons were similar in the two groups, regardless of cause of prior risk status. Despite the counting policy, most of these fetuses were dead by the time the mothers received medical attention. The study does not rule out a beneficial effect, but at best, the policy would have to be used by about 1250 women to prevent 1 unexplained antepartum late fetal death, and an adverse effect is just as likely. In addition, formal routine counting would use considerable extra resources.

In a randomised cross-over study, six patients with recurrent sustained ventricular tachycardia (VT) were treated with 3 regimens--amiodarone, amiodarone plus metoprolol, and amiodarone plus xamoterol. All patients had poor left ventricular function and were resistant to multiple drugs. Xamoterol (a partial beta-agonist) was more effective than metoprolol as adjuvant therapy to amiodarone in the control of recurrent sustained ventricular arrhythmias and was not associated with any clinical deterioration of ventricular function. Xamoterol was also more effective than metoprolol for suppression of VT at programmed stimulation and as effective as metoprolol for suppression of VT on exercise. Exercise tolerance was significantly greater during treatment with xamoterol/amiodarone than during treatment with metoprolol/amiodarone or with amiodarone alone.

In a multicentre study 711 patients were randomised to a group receiving calcium-heparin, 12,500 U, subcutaneously (360), or to a group receiving no heparin (351), beginning within 24 h of the onset of symptoms. 433 of these patients, admitted within 6 h, were given intravenous streptokinase (SK). Results were analysed for the in-hospital period. Calcium-heparin had no significant effects on the frequency of electrocardiographically documented ischaemic episodes or non-fatal reinfarction in the whole series; in the subgroup receiving SK, transient ischaemic episodes recurred in 14.2% of those treated with heparin vs 19.6% of the controls (p = 0.08). Mortality was significantly lower in the calcium-heparin treated patients, both in the overall groups (21/360 vs 35/351, p = 0.03) and in the SK subgroups (10/218 vs 19/215, p = 0.05). In 200 patients with first anterior myocardial infarction, it was possible to assess the effect of heparin on left ventricular mural thrombosis. On predischarge two-dimensional echocardiography, the prevalence of thrombus was significantly lower in the heparin group than in the control group (19/107 vs 34/93). Heparin also greatly reduced the incidence of thrombus formation in those who were thrombus-free on admission. Complications of heparin treatment were few.

To examine the potential role of fish oil supplementation in the prevention of restenosis after coronary angioplasty (PTCA), a randomised double-blind trial was conducted in 204 patients. The treatment group received 6 g/day of n-3 fatty acids, beginning 5.4 (SD 3.2) days before PTCA, and continuing for 6 months; the control group received olive oil placebo. Compliance was assessed by pill count and plasma levels of eicosapentaenoic acid (EPA). Restenosis was identified by symptoms and exercise testing and confirmed by angiography. PTCA was successful in 186 patients (93%). The incidence of angiographic restenosis was 34% in the fish oil group and 23% in the control group (relative risk 1.7, 95% CI 0.9-3.4). The lack of benefit of fish oil was not influenced by length of pretreatment, compliance with study medication, or the concentrations of plasma EPA achieved.

In a prospective study, 105 infants aged 3-12 months with acute otitis media were randomly assigned to one of three treatment groups: amoxycillin/clavulanate ('Augmentin') alone (36 patients), myringotomy plus placebo (35 patients), or augmentin plus myringotomy (34 patients). The last two groups were double-blinded. Bacterial pathogens, mainly Haemophilus influenzae (of which 20% were beta-lactamase producers) and Streptococcus pneumoniae, were isolated from 60% of the ear exudates and all isolates were sensitive to augmentin. Most of the infants improved clinically within 3-6 days irrespective of the treatment protocol. As judged by otoscopy, 60% of the patients receiving augmentin, with or without myringotomy, recovered completely compared with 23% of patients treated with myringotomy plus placebo. Treatment with augmentin was also more effective than myringotomy with regard to persistence of ear infection. In the myringotomy plus augmentin group closure of the incision and resolution of the discharge from the incision site was faster than in the myringotomy plus placebo group. The addition of myringotomy to augmentin did not seem to affect either the persistence of the infection after treatment or the residual middle ear effusion.

To examine whether hyperglycaemia impairs the absorption of sulphonylurea agents, glipizide, which is rapidly and completely absorbed, was measured in plasma from 12 healthy young subjects during various levels of experimentally-induced hyperglycaemia. An increase in the plasma glucose concentration above 7 mmol/l was associated with a dose-dependent delay in the absorption of glipizide; at a concentration above 11 mmol/l, the plasma glipizide concentration was reduced by 50%. The data indicate that hyperglycaemia may delay the absorption of sulphonylurea agents, probably because it impairs gastric motility and/or gastric emptying. This delay of absorption may be clinically relevant, since the efficacy of short-acting sulphonylureas is dependent upon the absorption rate of the drug.

In a double-blind study, 12 consecutive patients with acute promyelocytic leukaemia were randomised either to tranexamic acid (TA group) or to placebo (control group) for 6 days to see whether inhibition of fibrinolysis would reduce haemorrhage and transfusion requirements. The total study period was 14 days. In the TA group, there were fewer haemorrhagic episodes, as determined by a scoring system. Packed red cell transfusion requirements decreased; and fewer additional platelet concentrate transfusions were needed. These beneficial effects were more pronounced in the second week. There were no thromboembolic complications.

A new obstetric aid, the 'Birth Cushion' allows the parturient to sink into a supported squatting posture for the second stage of labour and delivery; it fits onto conventional delivery beds. A prospective, controlled trial of 427 primiparae compared the outcome of labour in women randomly allocated to squatting (218) or conventional semirecumbent (209) management. The squatting group had significantly fewer forceps deliveries (9% vs 16%) and significantly shorter second stages (median length of pushing 31 vs 45 min) than the semirecumbent group. There were fewer perineal tears, but more labial tears, in the squatting group. Apgar scores, blood loss, and post-partum vulvar oedema were similar in both groups. 82% of the women in the squatting group maintained upright positions for most of the second stage, and reported great satisfaction with the supported squatting position. The traditional birth posture of squatting can be easily adapted for modern labour management and has advantages for women in their first labour.

By means of loxiglumide, a potent and highly specific antagonist for cholecystokinin (CCK), the effects of blocking CCK receptors on gastrointestinal motility were investigated in a placebo-controlled study in healthy young men (aged 21-39, mean 24 years). Gallbladder contraction stimulated by ingestion of a liquid test meal was completely abolished by oral administration of loxiglumide 30 min before the test meal. Gastric emptying of radio-opaque markers ingested with the test meal was significantly accelerated by loxiglumide (area under the curve [markers x h] 33.3 [SEM 3.8] vs 17.9 [2.7] after placebo). No effect of loxiglumide was found on small-bowel transit time, but 7 days' treatment with oral loxiglumide (800 mg three times daily) significantly shortened colonic transit time (29.4 [4.1] h after placebo, 15.0 [3.4] h after loxiglumide). It is concluded that CCK is an important mediator of meal-induced gallbladder contraction and is involved in the regulation of gastrointestinal motility in man.

In a prospective randomised trial, 249 patients who had aortocoronary vein bypass surgery were assigned either to a platelet inhibitory drug regimen or to standard anticoagulant therapy. Treatment was replaced by placebo in half of the patients in each group after 3 months. The platelet inhibitory drug regimen--very low-dose aspirin combined with dipyridamole--was as effective as standard anticoagulant therapy to prevent early and late graft occlusion. Death, myocardial infarction, and severe bleeding occurred significantly more often in patients receiving anticoagulants, whereas mild drug-related gastrointestinal and cerebral side-effects were more common in patients taking platelet inhibitory drugs. Antithrombotic treatment should be continued for at least 1 year after coronary artery bypass graft surgery.

103 patients with acute airflow obstruction (56 asthma, 47 chronic obstructive pulmonary disease [COPD]) completed a double-blind trial of nebulised bronchodilator treatment in a hospital accident and emergency department. Each patient was randomised to receive either 10 mg of salbutamol nebuliser solution in 2 ml of saline or 10 mg of salbutamol in 2 ml (0.5 mg) of preservative-free ipratropium bromide. Peak flow rate (PFR) was recorded before treatment and 1 hour after beginning nebulised treatment. In 23 asthmatic patients given salbutamol alone PFR rose by a mean 31% 1 hour after treatment whereas in 33 such patients given combined treatment it rose by a mean 77% (95% confidence interval for the difference 8-84%). Patients whose PFR was below 140 l/min at entry gained maximum benefit from the combined treatment. For COPD patients the PFR rise was almost identical for both treatments. In acute asthma the immediate PFR response to a mixture of salbutamol and ipratropium bromide was better than the response to nebulised salbutamol alone. For COPD patients, the two treatments were of equal benefit.