Selective decontamination of the digestive tract (SDD), by means of non-absorbable antibiotics, to prevent infection in intensive-care units (ICUs) remains controversial; there is evidence that the regimen reduces the incidence of secondary infection, but no convincing reduction in morbidity or mortality has been shown and the costs and effect on microbial resistance patterns need further study. In a double-blind, placebo-controlled trial, we have tried to find out whether SDD should be used routinely in all ICU patients at high risk of secondary infection. All patients admitted to the ICU who were thought likely to stay in the unit for at least 5 days and to need intubation for longer than 48 h were enrolled and randomly allocated to groups receiving placebo or SDD (amphotericin, colistin, and tobramycin applied to the oropharynx and enterally); all patients received intravenous cefotaxime for 72 h. Of 322 patients randomised, 83 were withdrawn (80 ICU stay or duration of intubation too short, 3 protocol violations). 239 medical, trauma, and surgical patients completed the trial period (114 SDD, 125 placebo). There were no differences between SDD and placebo groups in incidence of infection (30 [26%] vs 43 [34%] patients; p = 0.22), duration of ICU stay (mean 16.2 [14.3] vs 16.8 [12.3] days), hospital stay (29.9 [SD 25.0] vs 31.9 [22.2] days), or mortality (21 [18%] vs 21 [17%]). SDD substantially increased the costs of intensive care. Mechanisms other than bacterial colonisation of the gut may bring about substantial numbers of secondary infections in ICUs. Routine use of SDD in multidisciplinary ICUs cannot be recommended.

There has been considerable interest in traditional Chinese herbal therapy (TCHT) as a new treatment for atopic dermatitis. To establish the efficacy and safety of this treatment, a daily decoction of a formula containing ten herbs that has been found to be beneficial in open studies was tested in a double-blind placebo-controlled study. 40 adult patients with longstanding, refractory, widespread, atopic dermatitis were randomised into two groups to receive 2 months' treatment of either the active formulation of herbs (TCHT) or placebo herbs, followed by a crossover to the other treatment after a 4-week washout period. The main outcome measures were extent and severity of erythema and surface damage as judged by standardised body scores. The patients' own assessments of the overall response to treatment were also sought. The geometric mean score for erythema at the end of active treatment was 12.6 (95% confidence interval [CI] 5.9 to 22.0) and at the end of the placebo phase was 113 (65 to 180). The geometric mean score for surface damage was 11.3 (5.8 to 21.8) and 111.0 (68 to 182), respectively. The 95% CI for the mean geometric ratio for the two values with active treatment was 0.04 to 0.22 for erythema (p less than 0.0005) and 0.04 to 0.27 for surface damage (p less than 0.0005). Of the 31 patients who completed the study and expressed a preference, 20 preferred that phase of the trial in which they received TCHT whereas 4 patients preferred placebo (p less than 0.02). There was a subjective improvement in itching (p less than 0.001) and sleep (p less than 0.078) during the TCHT treatment phase. No side-effects were reported by the patients although many commented on the unpalatability of the decoction. TCHT seems to benefit patients with atopic dermatitis. Palatability of the treatment needs to be improved and its safety assured.

The cardiovascular actions of the magnesium ion at pharmacological concentrations include coronary and systemic vasodilatation, platelet inhibition, and antiarrhythmic effects. Magnesium has also been reported to protect myocardial tissue in experimental models of ischaemia and reperfusion. Several small clinical trials in suspected acute myocardial infarction have suggested that early mortality can be reduced by intravenous infusion of magnesium salts in the acute phase, but none has been of sufficient size to be conclusive. We therefore conducted a randomised, double blind, placebo controlled study in 2316 patients with suspected acute myocardial infarction who received either intravenous magnesium sulphate (8 mmol over 5 min followed by 65 mmol over 24 h) or physiological saline. The primary outcome measure was 28-day mortality, which was ascertained in 99.3% of patients. The groups were well balanced for prognostic factors. By intention-to-treat analysis mortality from all causes was 7.8% in the magnesium group and 10.3% in the placebo group (2p = 0.04), a relative reduction of 24% (95% confidence interval 1-43%). Within the coronary care unit the incidence of left ventricular failure was reduced by 25% (7-39%) in the magnesium group (2p = 0.009). There was no significant difference between the groups in the incidence of heart block or the use of antiarrhythmic drugs, direct-current cardioversion, or temporary pacing. Myocardial infarction was confirmed in 65% of each group, with closely similar rises in cardiac enzymes. The side-effects of magnesium treatment were transient flushing, related to speed of injection of the loading dose, and an increased incidence of sinus bradycardia (2p = 0.02). Exploratory subgroup analyses of 28-day mortality did not indicate any effect modification by thrombolysis or aspirin, or by previous treatment with beta blockers, calcium antagonists, or diuretics. Intravenous magnesium sulphate is a simple, safe, and widely applicable treatment. Its efficacy in reducing early mortality of myocardial infarction is comparable to, but independent of, that of thrombolytic or antiplatelet therapy.

By instructing patients in how to deal with their disease financial demands on health services may be reduced. 100 consecutive patients (aged 48 to 89) admitted to a general medical ward in Denmark with chronic obstructive pulmonary disease (COPD) were allocated randomly to receive either "personalized hospital practice" (PHP), which includes training in aspects of their disease, or standard hospital practice. Changes in "consumption" of health services per patient from 1 year before until 1 year after the intervention admission were evaluated in 82 (PHP group 42, controls 40) patients who completed the intervention phase. Each group contained about the same percentage of asthmatics and smokers. The increase in consumption of health services after intervention was on average Kr15,298 per patient per year less in the PHP group than in the control group (p = 0.048, Wilcoxon test). Consumption of general practitioner services was significantly increased in the control group compared with the PHP group (mean [95% Cl] Kr1346 [549 to 2143] vs -89 [-423 to 245] per patient per year; p = 0.001, Wilcoxon test). These differences could not be explained by changes in smoking habits. PHP reduces the consumption of health services by patients with COPD, probably by increasing patients' knowledge of disease and hence their ability to manage themselves.

There is much evidence that the development of allergic disorders may be related to early exposure of allergens, including those in breastmilk. We have tried to find out whether avoidance of food and inhaled allergens in infancy protects against the development of allergic disorders in high-risk infants. In a prenatally randomised, controlled study 120 infants with family history of atopy and high (greater than 0.5 kU/l) cord-blood concentrations of total IgE were allocated randomly to prophylactic and control groups. In the prophylactic group (n = 58), lactating mothers avoided allergenic foods (milk, egg, fish, and nuts) and avoided feeding their infants these foods and soya, wheat, and orange up to the age of 12 months; the infants' bedrooms and living rooms were treated with an acaricidal powder and foam every 3 months, and concentrations of Dermatophagoides pteronyssinus antigen(Der p l) in dust samples were measured by enzyme-linked immunosorbent assay. In the control group (n = 62), the diet of mothers and infants was unrestricted; no acaricidal treatment was done and Der p l concentrations were measured at birth and at 9 months. A paediatric allergy specialist unaware of group assignment examined the infants for allergic disorders at 10-12 months. Odds ratios were calculated by logistic regression analysis for various factors with control for other confounding variables. At 12 months, allergic disorders had developed in 25 (40%) control infants and in 8 (13%) of the prophylactic group (odds ratio 6.34, 95% confidence intervals 2.0-20.1). The prevalences at 12 months of asthma (4.13, 1.1-15.5) and eczema (3.6, 1.0-12.5) were also significantly greater in the control group. Parental smoking was a significant risk factor for total allergy at 12 months whether only one parent smoked (3.97, 1.2-13.6) or both parents smoked (4.72, 1.2-18.2).

There has been much debate about reports that some insulin-treated diabetic patients lose awareness of hypoglycaemic symptoms on changing from porcine to human insulin. In a double-blind, crossover study, we sought differences between porcine and human insulin in the frequency and characteristics of hypoglycaemic episodes among patients who reported a reduction of awareness of hypoglycaemia after changing treatment. We studied 50 patients referred by their physicians because of complaints of lack of awareness of hypoglycaemia on human insulin. They had had diabetes for a mean of 20 (SD 12) years and 70% had good or acceptable glycaemic control. Each patient was treated in a double-blind manner for four 1-month periods, two with human and two with porcine insulin, in random order. Only 2 patients correctly identified the sequence of insulin treatments used; 8 or 9 would have been expected to do so by chance alone. The mean percentage of hypoglycaemic episodes associated with reduced or absent awareness was 64% (SD 30%) for human insulin and 69% (31%) for porcine insulin. We could find no statistically significant differences between the insulin species with respect to glycaemic control or the frequency, timing, severity, or awareness of hypoglycaemia. Reduced hypoglycaemia awareness is common with both human and porcine insulins.

Poxviruses have many useful features as vectors for genes that carry immunising antigens from other viruses, such as ease of production and induction of cellular and humoral immunity, but there is concern about the safety of vaccinia virus. We turned to an avian poxvirus (canarypox); this virus undergoes abortive replication in mammalian cells that enables presentation of early gene products to the immune system. Canarypox virus was used as a vector for the rabies glycoprotein G gene. The safety and efficacy of the recombinant (ALVAC-RG; vCP65) were tested in several animal species, then it was subjected to a phase 1 clinical trial. Twenty-five volunteers were randomly assigned to subcutaneous injections of the recombinant (three groups [A, B, and C] received two doses each of 10(3.5), 10(4.5), and 10(5.5) tissue-culture infectious doses50, respectively) or of human diploid cell culture vaccine (HDC; 6.52 international potency units per dose). 28 days after the second dose, all nine ALVAC-RG group-C subjects and two of three group-B subjects had rabies neutralising antibody concentrations of at least 0.5 IU/ml, the level associated with protection in animals. Although the geometric mean titre of these antibodies at that time was lower in group C than in the ten HDC recipients (4.4 [range 0.9-12.5] vs 11.5 [4.7-25.3] IU/ml), a single booster dose at 6 months induced a recall response in volunteers primed with either vaccine. Side-effects associated with ALVAC-RG were mild and of short duration and occurred at similar frequency to those of HDC vaccine. This study has shown the potential of non-replicating poxviruses as vectors for vaccination in human beings. Trials of canarypox-virus recombinants at higher doses and by other routes of administration are needed.

The increasing popularity of warm heart surgery led us to assess the effect of temperature during cardiopulmonary bypass (CPB) on neuropsychological function after coronary surgery. 34 patients enrolled in a randomised trial of normothermic versus hypothermic CPB were subjected to a battery of psychomotor and memory tests before and after their operations. The mean nasopharyngeal temperature for warm CPB was 34.7 (SD 0.5) degrees C and that for hypothermic CPB was 27.8 (2.0) degrees C. In all seven neuropsychological tests the postoperative scores were better in the warm CPB than in the hypothermic group, although only one difference achieved significance (trial-making test A; p less than 0.023). Thus, neurological function after normothermic CPB seems to be no worse than that after hypothermic procedures.

The spermicide nonoxynol-9 (N-9) has been used as a contraceptive for over 30 years, but the use of a vaginal spermicide and condoms for the prevention of sexually transmitted infections has not been examined in randomised studies. We report a single-blind randomised field trial to assess the effect of N-9 film on the rate of gonococcal and chlamydial cervical infection in women at high risk of these diseases. 343 women were randomly assigned to use either condoms and N-9 (186 women) or condoms and a placebo (157). Compliance with condom use was much the same in the two groups. Overall, N-9 reduced the rate of cervical infection by 25% (rate ratio [RR] 0.75, 95% confidence interval [Cl] 0.5-1.1); in women who used N-9 for more than 75% of their coital acts the infection rate was reduced by 40% (RR 95% Cl 0.3-1.0). The rate of yeast vulvovaginitis or genital ulcers was not higher in N-9 users than in placebo users, but the rate of symptomatic irritation was increased by 70% (RR 95% Cl 1.1-2.6) among N-9 users. Condom use was more protective against cervical infection than N-9 use. The rate of infection was 50% (RR 95% Cl 0.3-0.7) lower with 75% than with 0-50% condom compliance. The use of a vaginal N-9 spermicide with condoms whenever possible seems to be a better strategy than the use of condoms only for prevention of gonococcal and chlamydial cervical infection.

There is controversy about whether the lack of response of some chronic pain to opioid treatment is absolute or relative. It is widely believed that nociceptive pain is responsive to opioids whereas neuropathic pain tends not to be. We have used a method of patient-controlled analgesia (PCA) with simultaneous nurse-observer measurement of analgesia, mood, and adverse effects to address these issues. Ten patients with chronic pain were given morphine at two concentrations (10 and 30 mg/ml) by PCA in two separate sessions in a double-blind randomised crossover study. Before the study a clinical judgment was made as to whether each pain was nociceptive or neuropathic. Seven patients showed good analgesic responses (more than 70 mm pain relief on a visual-analogue scale) of pain at rest, two patients poor responses (less than 30 mm pain relief), and one a moderate response with both concentrations (30-70 mm pain relief). The response to morphine was consistent (greater and faster relief with the higher concentration) in nine patients. Two patients had pain on movement that responded moderately to low-concentration morphine and well to the higher concentration. All patients with pains judged to be nociceptive showed good analgesic responses compared with half of those with neuropathic pain. There was no evidence that analgesic responses in patients with neuropathic pain were due to changes in mood. This PCA method is a quick and efficient tool to determine the consistency of the analgesic response. Such consistency can guide the clinician as to whether continued or higher-dose opioid treatment will produce good analgesia. An inconsistent response points to the use of other pain-relieving strategies.

In the UK, psychiatric care of patients with acute and chronic disorders has increasingly moved from hospital to the community. We have evaluated in a controlled trial patients with severe mental illness, who were assigned to early intervention by community services or to standard hospital treatment. 100 patients aged 16 to 65 years presenting as psychiatric emergencies to an inner London teaching hospital were randomly allocated to a multidisciplinary community-based team (n = 48) or conventional hospital-based psychiatric services (n = 52) and assessed over a 3-month period. Ratings of psychopathology and social functioning were made before treatment and after 2, 4, and 12 weeks by independent assessors. 85 patients completed all assessments, and all patients had evaluable data beyond 2 weeks. 3 patients died during the study, 2 from natural causes and 1 from an accident. Patients referred to the community service showed greater improvement in symptoms and were more satisfied with services than those in the hospital-based service. Patients treated in the hospital-based service spent eight times as many days as psychiatric inpatients as those treated in the community-based service. Patients both prefer and seem to benefit from community-based psychiatric care, and our early-intervention community service might be a good model for such care.

Sulphasalazine extends remissions and lessens disease activity during relapses of ulcerative colitis, but it also causes many adverse side-effects. The adverse reactions are mostly attributable to the sulphapyridine carrier moiety rather than the active principle 5-aminosalicylic acid (5-ASA), so agents to deliver 5-ASA to the colon by other means have been designed. We have compared the efficacy and tolerability of two such agents, olsalazine and mesalazine, in maintenance therapy of ulcerative colitis. 100 patients with ulcerative colitis in remission were recruited at one centre and assigned randomly to treatment with olsalazine (Dipentum; 1.0 g daily) or mesalazine (Asacol, with Eudragit-S coating; 1.2 g daily). Compliance, biochemical and haematological variables, and clinical evidence of disease activity were assessed every 3 months for 12 months by observers unaware of treatment allocation. In intention-to-treat analysis, which included as treatment failures patients withdrawn for protocol violations, adverse reactions, intercurrent illness, or non-compliance as well as those with relapses of ulcerative colitis, the olsalazine group had a significantly lower rate of treatment failure than the mesalazine group (12/49 [24%] vs 23/50 [46%]; p = 0.025). Analysis restricted to 64 patients still in remission at 1 year and 18 with relapses also showed a significant difference in relapse rate (olsalazine 5/42 [12%] vs mesalazine 13/40 [33%]; p = 0.024). Both drugs were well tolerated; only 9 patients reported substantial side-effects. Olsalazine was clearly superior to mesalazine in prevention of relapses in ulcerative colitis, especially in patients with left-sided disease.

Axillary dissection in early breast cancer remains controversial because of its substantial side-effects and because its value with respect to recurrence or survival has not been unequivocally proven. Between 1982 and 1987, 658 patients were included in a prospective randomised comparison of lumpectomy alone with lumpectomy plus axillary dissection. All patients had a unilateral breast tumour not exceeding 3 cm in diameter and lymph-node involvement or metastases. Radiation therapy was given to both groups. The two groups of patients were similar with respect to mean age, TNM stage, and presence of hormonal receptors. Median follow-up was 54 months. 5-year survival of the patients was 94.2% (95% Cl: 92.1-96.4). There was a significant advantage in survival in the axillary dissection group (p = 0.014). Recurrence of tumour in the breast was similar in the two groups but visceral metastases, supraclavicular metastases, and lymph-node recurrences were less frequent in the axillary dissection group. Survival was related to the age of the patients (p = 0.005), the presence of positive nodes (p = 0.006), the histological grading (p less than 0.0001), and the presence of hormonal receptors (progesterone p = 0.0008, oestrogen p less than 0.0001). Treatment-adjusted relative risk was 2.4 (95% Cl: 1.3-4.2). The findings show that axillary dissection is justified for treatment of small breast cancers, although whether the better survival is due to axillary clearance itself or to adjuvant treatment for lymph-node involvement is unclear.