A multicentre randomised controlled trial and economic evaluation of ion-exchange water softeners for the treatment of eczema in children: the Softened Water Eczema Trial (SWET).

OBJECTIVES: To determine whether installation of an ion-exchange water softener in the home could improve atopic eczema in children and, if so, to establish its likely cost and cost-effectiveness. DESIGN: An observer-blind, parallel-group randomised controlled trial of 12 weeks duration followed by a 4-week observational period. Eczema was assessed by research nurses blinded to intervention at baseline, 4 weeks, 12 weeks and 16 weeks. The primary outcome was analysed as intent-to-treat, using the randomised allocation rather than actual treatment received. A secondary per-protocol analysis excluded participants who failed to receive their allocated treatment and who were deemed to be protocol violators. SETTING: Secondary and primary care referral centres in England (UK) serving a variety of ethnic and social groups and including children living in both urban and periurban homes. PARTICIPANTS: Three hundred and thirty-six children (aged 6 months to 16 years) with moderate/severe atopic eczema, living in homes in England supplied by hard water (≥ 200 mg/l calcium carbonate). INTERVENTIONS: Participants were randomised to either installation of an ion-exchange water softener plus usual eczema care (group A) for 12 weeks or usual eczema care alone (group B) for 12 weeks. This was followed by a 4-week observational period, during which water softeners were switched off/removed from group A homes and installed in group B homes. Standard procedure was to soften all water in the home, but to provide mains (hard) water at a faucet-style tap in the kitchen for drinking and cooking. Participants were therefore exposed to softened water for bathing and washing of clothes, but continued to drink mains (hard) water. Usual care was defined as any treatment that the child was currently using in order to control his or her eczema. New treatment regimens used during the trial period were documented. MAIN OUTCOME MEASURES: Primary outcome was the difference between group A and group B in mean change in disease severity at 12 weeks compared with baseline, as measured using the Six Area, Six Sign Atopic Dermatitis (SASSAD) score. This is an objective severity scale completed by blinded observers (research nurses) unaware of the allocated intervention. Secondary outcomes included use of topical medications, night-time movement, patient-reported eczema severity and a number of quality of life measures. A planned subgroup analysis was conducted, based on participants with at least one mutation in the gene encoding filaggrin (a protein in the skin thought to be important for normal skin barrier function). RESULTS: Target recruitment was achieved (n = 336). The analysed population included 323 children who had complete data. The mean change in primary outcome (SASSAD) at 12 weeks was -5.0 [standard deviation (SD) 8.8] for the water softener group (group A) and -5.7 (SD 9.8) for the usual care group (group B) [mean difference 0.66, 95% confidence interval (CI) -1.37 to 2.69, p = 0.53]. The per-protocol analysis supported the main analysis, and there was no evidence that the treatment effect varied between children with and without mutations in the filaggrin gene. No between-group differences were found in the three secondary outcomes that were assessed blindly (use of topical medications; night-time movement; proportion showing reasonable, good or excellent improvement). Small, but statistically significant, differences in favour of the water softener were found in three of the secondary outcomes that were assessed by participants [Patient-Oriented Eczema Measure (POEM); well-controlled weeks (WCWs); Dermatitis Family Index (DFI)]. The results of the economic evaluation, and the uncertainty surrounding them, suggest that ion-exchange water softeners are unlikely to be a cost-effective intervention for children with atopic eczema from an NHS perspective. CONCLUSIONS: Water softeners provided no additional benefit to usual care in this study population. Small, but statistically significant, differences were found in some secondary outcomes as reported by parents, but it is likely that such improvements were the result of response bias. Whether or not the wider benefits of installing a water softener in the home are sufficient to justify the purchase of a softener is something for individual householders to consider on a case-by-case basis. This trial demonstrated overwhelming demand for non-pharmacological interventions for the treatment of eczema, and this is something that should be considered when prioritising future research in the field. TRIAL REGISTRATION: Current Controlled Trials ISRCTN71423189. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 15, No. 8. See the HTA programme website for further project information. Results of this trial are also published at www.plosmedicine.org.

Clinical teaching in paediatrics: understanding perceptions, motives and concerns.

BACKGROUND: Children and young people are used as cases and standardised patients in clinical exams and teaching courses. Consultation with them suggests that education and training are areas they feel they should actively participate in. AIMS: To examine the perceptions, motives and concerns of children and young people participating in exam-focused clinical teaching, and to compare these views with those of their parents, trainees and tutors. METHODS: Consultation and a pilot study were used to design an anonymised questionnaire with 5-point Likert scales and free text answers. This was sent to 112 children and young people, their parents, and tutors and trainees attending a clinical teaching course. Results were analysed using the Mann-Whitney U test. RESULTS: 71% of the questionnaires sent to children and young people and their parents were completed. For children and young people the major reasons for taking part were the enjoyment of helping people to learn (92% agreement) and wanting to "give something back" (85% agreement). Parents put significantly more emphasis on giving something back than anything else. Tutors and trainees felt the chance for children and young people to earn pocket money was their most important motivation. The major problem highlighted was that it is tiring being repeatedly examined. All children and young people and their parents said that they would participate in future clinical teaching. CONCLUSIONS: This study demonstrates that in the context of well-planned, structured clinical teaching, most children and young people are primarily motivated to participate to help educate doctors.

Efficacy and acceptability of a new topical skin lotion of sodium cromoglicate (Altoderm) in atopic dermatitis in children aged 2-12 years: a double-blind, randomized, placebo-controlled trial.

BACKGROUND: Atopic dermatitis (AD) is a common inflammatory allergic disease of children. The primary anti-inflammatory therapy is topical steroids. An effective treatment without the topical and systemic adverse effects of corticosteroids would be useful. Topical formulations of sodium cromoglicate have been researched in the past, but without consistent results. We report a trial of a new aqueous skin lotion of sodium cromoglicate (Altoderm) in children with AD. OBJECTIVES: To compare the efficacy, safety and acceptability of Altoderm lotion with a placebo control in the treatment of AD in children. METHODS: A double-blind, controlled study in which children aged 2-12 years with AD were randomized to 12 weeks of treatment with a lotion containing 4% sodium cromoglicate (Altoderm) or the lotion base. To be included subjects had to have a SCORAD score of > or = 25 and < or = 60 at both of two clinic visits 14 days apart. Subjects continued using existing treatment which included emollients and topical steroids. The primary outcome was the change in the SCORAD score. The two groups were compared for the change in the SCORAD score from the second baseline visit to the visit after 12 weeks of treatment using an analysis of variance. Secondary outcome measures included parents' assessment of symptoms, usage of topical steroids recorded on daily diary cards, and final opinions of treatment by parent and clinician. Parents were asked about adverse effects at each clinic visit and the responses recorded. RESULTS: Fifty-eight children were randomized to Altoderm and 56 to placebo and all were included in the intention-to-treat analysis. The mean +/- SD SCORAD scores at baseline were 41.0 +/- 9.0 (Altoderm) and 40.4 +/- 8.73 (placebo). These scores were reduced after 12 weeks by 13.2 (36%) with Altoderm and by 7.6 (20%) with placebo. The difference of 5.6 (95% confidence interval 1.0-10.3) is statistically significant (P = 0.018). Diary card symptoms improved with both treatments but the improvement was greater in the Altoderm-treated patients. Topical steroid usage was reduced in both groups and was larger in the Altoderm-treated patients. The differences were statistically significant for the mean of all symptoms, the overall skin condition and use of topical steroids. Those for itching and sleep loss were not. Treatment-related adverse events were reported in 11 subjects (Altoderm seven, placebo four). Most of these referred to irritation, redness and burning at the site of application. There were four reports of erythema and pruritus (Altoderm three, placebo one), and three reports of application site burning (Altoderm two, placebo one). None was reported as severe or very severe. CONCLUSIONS: These results show a clinically useful benefit of this sodium cromoglicate lotion in children with moderately severe AD.

Plasma histamine and clinical tolerance to infused histamine in normal, atopic and urticarial subjects.

Five subjects with a recent history of urticaria (U), five atopic (A) subjects and a non-atopic (NA) control group were given intravenous infusions of histamine starting at 0.05 micrograms/kg/min, increasing by 0.05 micrograms/kg/min every 30 minutes to a maximum of 0.35 micrograms/kg/min. Plasma histamine levels were monitored every 15 minutes. The infusion was stopped when an objective clinical endpoint was reached, involving either evidence of peripheral vasodilatation (rise of skin temperature by at least 1 degree C) or a 20% fall of peak expiratory flow rate. There were no significant differences in resting plasma histamine in the three groups. Those with urticaria reached the clinical endpoint at a lower infusion rate than non-atopic subjects (U 0.22 +/- 0.02 micrograms/kg/min; A 0.26 +/- 0.02 micrograms/kg/min; NA 0.32 +/- 0.2 micrograms/kg/min. p less than 0.008) they also received a lower total histamine dose (U 1.12 +/- 0.33 mg; A 1.42 +/- 0.38 mg, NA 2.2 +/- 0.51 mg, p less than 0.008). Atopic subjects with a history of asthma, eczema or rhinitis also tolerated histamine poorly, some subjects reaching a clinical endpoint while the plasma histamine level was still relatively low (U 1.52 +/- 0.4 ng/ml, A 0.85 +/- 0.19 ng/ml, NA 1.4 +/- 0.44 ng/ml, p = 0.05). After the histamine infusion was stopped, the fall in the blood level of histamine was slower in urticarial subjects than in the other two groups, with a half-life of 6.2 +/- 1.3 min (A 3.0 +/- 1.2 min, NA 4.0 +/- 0.7 min, p less than 0.02). There were thus differences in the metabolism of histamine in our non-atopic urticarial subjects and increased histamine sensitivity in atopic subjects which require further study.

Measurement of airborne mite antigen in homes of asthmatic children.

The airborne concentration of major house dust mite antigen Der p1 was measured by low volume sampling (2 litres/min) in the homes of 68 allergic, asthmatic children. The presence of detectable airborne antigen was strongly associated with sensitivity to the mite, whereas there was no significant relation between sensitivity and the previously recommended threshold level of 2 micrograms Der p1 per g carpet dust. There was a significant association with lower threshold levels in carpet dust (0.5 microgram/g) but at no level was the association as strong as that with air measurements. Concentrations of airborne antigen were higher in rooms with wool carpets than in those with synthetic carpets or hard floors, but there was no significant difference between the dust levels of Der p1 in the two carpet types. Air sampling is a more appropriate method of assessing antigen exposure than dust sampling for asthmatic patients.

Effect of artificial food colours on childhood behaviour.

We performed an objective evaluation of 39 children whose behaviour was observed by their parents to improve on an artificial food additive free diet and to deteriorate with dietary lapses. Only 19 children completed a double blind placebo controlled challenge study with artificial food colours. In these children food colours were shown to have an adverse effect on a daily Conners' rating of behaviour, but most parents could not detect these changes. A pharmacological mechanism of food additive intolerance is proposed to explain these effects.

Survey of colourings and preservatives in drugs.

OBJECTIVE: To assess the prevalence of colourings and preservatives in drug formulations in the United Kingdom. DESIGN: Postal survey. PARTICIPANTS: All pharmaceutical manufacturers in the United Kingdom were requested to supply data on drug formulations with particular regard to the content of colourings and preservatives. MAIN OUTCOME MEASURE: Prevalence in proprietary drugs of colourings or preservatives, or both, that have been implicated in adverse reactions. Computation of a list of formulations of bronchodilators, antihistamines, and antibiotics that are free of such additives. RESULTS: A total of 118 out of 120 pharmaceutical companies supplied the data requested. In all, 2204 drug formulations were analysed and found to contain 419 different additives, of which 52 were colourings and preservatives that have been implicated in adverse reactions; 930 formulations contained such an additive. Tartrazine was the fourth most commonly occurring colouring, being present in 124 drug formulations. CONCLUSION: Many drugs contain additives that help to identify them and prolong their shelf life but are implicated in adverse reactions in some people. Some form of labelling of drug additives would enable these people to avoid drugs containing such additives.

Ceftazidime in the treatment of neonatal infection.

The efficacy of ceftazidime in the treatment of neonatal sepsis was studied in 42 low birthweight premature babies. Forty-nine courses of ceftazidime (25 mg/kg bd, iv or im were administered. In 19 babies, treatment was stopped after 48 h, the remainder were treated for 5 days or more. Six neonates had bacteriological evidence of infection, one other was pyrexial and 29 had radiological evidence compatible with respiratory tract infection. Eight of the study population died. Only one death was attributed to infection which arose 3 days after completion of a 5-day course of ceftazidime. Two babies developed clinical signs of necrotizing enterocolitis (NEC). Clostridium difficile (7) and Cl. perfringens (2) were isolated from 34 post-treatment faecal samples but not from the two babies with NEC. No faecal sample contained Cl. difficile toxin. Post-treatment cultures from 12 neonates yielded ceftazidime-resistant micro-organisms. Ceftazidime therapy was not associated with significant alteration in serum alanine aminotransferase, urea, creatinine, protein or albumin. Four babies had an eosinophilia, three transient and one following two intrauterine transfusions. Coombs' tests were performed on 17 babies. There were no false positives. The abnormal clotting studies observed in one baby were not due to ceftazidime. In a concurrent pharmacokinetic study, the half-life of ceftazidime was 7.4 (SD +/- 4.1) h following iv administration. Other pharmacokinetic values were C max 74 (SD +/- 20) mg l-1 trough concentration 20 (SD +/- 10) mg l-1. Total body clearance ranged from 0.13 to 2.10 ml min-1 per kg and increased with increasing postnatal age.(ABSTRACT TRUNCATED AT 250 WORDS)