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.

Relationship between psychological well-being and lung health status in patients with bronchiectasis.

Patients with bronchiectasis often complain of abnormal tiredness, difficulty in concentrating or low spirits. This study was carried out to examine levels of anxiety and depression in bronchiectasis and their relationship with other measures of lung health. One hundred and eleven patients with bronchiectasis determined by high-resolution computed tomography (CT) scan were studied using a range of physiological and psychological outcome measures. Patients completed anxiety and depression, health status (quality of life), fatigue and dypnoea questionnaires. Lung function was measured and exercise capacity was assessed using a shuttle walk test. Anxiety and depression scores formed a continuum. Moderate-severe anxiety was more frequent than equivalent levels of depression (17 vs 9% of patients). Anxiety and depression scores were associated with perceived health status (r=0.33 and 0.55). Neither anxiety nor depression was associated with the extent of bronchiectasis on CT scan. Depression was correlated with breathlessness and exercise performance (r=0.33 and 0.40), but anxiety was not. The correlation between depression and exercise performance was not simply due to the influence of somatic items in the depression questionnaire. We conclude that anxiety and depression are quite common in bronchiectasis in that 34% of patients had elevated scores for anxiety depression or both. The non-somatic components of depression were linked to dyspnoea and exercise performance, but anxiety was only related to perceived health. Therefore, treatment aimed at reducing symptoms and improving exercise capacity will not reduce levels of anxiety which need alternative therapy.

Magnetic resonance angiography: the nuts and bolts.

Magnetic resonance angiography (MRA) has matured into an extremely reliable and valuable diagnostic vascular tool. We are now able to acquire clinically diagnostic angiograms in all the major vascular territories by using MRA, thereby replacing invasive angiography. This paradigm shift has enormous clinical and financial ramifications, as MRA is safer, cheaper, and far more convenient for our patients than invasive angiography. Future magnetic resonance imaging research developments that are on the verge of being incorporated into clinical practice include real-time magnetic resonance fluoroscopy and endovascular therapeutic ability. It should therefore be incumbent upon the vascular and interventional community to embrace this powerful technology by collaborating and integrating with those physicians who possess the skills to perform high-quality magnetic resonance imaging. This article provides basic key fundamental concepts and protocol guidelines for state-of-the art MRA performance and elucidates future directions of this technology as it pertains to the interventional and vascular radiologist.

The left ventricular dysfunction questionnaire (LVD-36): reliability, validity, and responsiveness.

OBJECTIVE: To examine the reliability, validity, and responsiveness of a new health status measure (LVD-36) for patients with left ventricular dysfunction which was designed with emphasis on content validity, clarity, brevity, and ease of use. DESIGN: At baseline, patients completed the LVD-36 and a range of measures reflecting general health and disease severity. The LVD-36 was repeated after one week. After six months, it was repeated again, along with a transition question to measure global changes in health. SETTING: Patients were recruited from the cardiology and general medical clinics at a south west London hospital. PATIENTS: 60 patients with chronic left ventricular dysfunction. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Short form 36 questionnaire (SF-36), Minnesota living with heart failure questionnaire (LIhFE), New York Heart Association criteria, and exercise performance and echocardiographic tests. RESULTS: The LVD-36 showed good internal consistency (kappa = 0.95) and repeatability (r(i) = 0.95). Its scores were significantly associated with SF-36 mental and physical component scores (r = -0. 48 and -0.75; p < 0.0001), with exercise capacity (r = -0.52; p < 0. 0001), and with systolic shortening fraction (r = -0.27; p < 0.05). Change in the LVD-36 over six months was associated with change in overall health (F = 5.7; p < 0.001). In tests of validity and responsiveness, the LVD-36 performed similarly to or marginally better than the LIhFE. CONCLUSIONS: The LVD-36 showed a high level of reliability and validity, and appears to measure changes in health. It provides a short, simple, valid, and reliable measure of health status in patients with left ventricular dysfunction.

A conformationally-constrained MHC class II I-Ag7-derived peptide protects NOD mice from the development of diabetes.

Allele-specific peptide vaccination against disease-associated MHC class II molecules is a promising new strategy for modulating self-antigen presentation to autoreactive T cells in autoimmune diseases. To evaluate the potential of this approach for treatment of insulin-dependent diabetes mellitus (IDDM), we have designed a cyclic peptide vaccine, DiavaX, from the third hypervariable region of the beta-chain of the NOD mouse MHC class II I-Ag7. NOD mice were treated at 5 and 9 weeks of age with 100 microg DiavaX emulsified in alum, a control peptide in alum, or alum alone. At the end of the study, 87% of alum treated mice had developed diabetes, compared with only 28% of DiavaX-treated mice. None of the control peptides, including a linear I-Ag7, a scrambled cyclic I-Ag7, or an analogous cyclic I-Aspeptide, reduced the incidence of diabetes, demonstrating that the protective effect of DiavaX is conformationally dependent and both allele- and sequence-specific. DiavaX treatment did not cause any general immune suppression, but did induce peptide-specific antibodies and memory T cells. DiavaX-induced protection from diabetes was associated with the maintenance of a non-destructive islet-associated autoimmune response. These data indicate that a conformationally constrained peptide from the disease-associated MHC represents a potential vaccine candidate for the prevention of clinical IDDM.

Systemic markers of inflammation in stable bronchiectasis.

Patients with bronchiectasis have an active local and systemic inflammatory response during infective exacerbations. Systemic markers of inflammation were investigated during a stable phase of their illness, because continued inflammation could affect their general health and be involved in disease progression. The relationship between levels of various systemic markers of inflammation and extent of disease on computed tomographic scan, lung function, sputum bacteriology and health related quality of life (HRQoL) was investigated in 87 noncystic fibrosis bronchiectasis patients. Several markers were elevated and correlated with the extent of disease and poor lung function. The total white cell count, neutrophil count and erythrocyte sedimentation rate correlated with both disease measures. Sputum bacteriology did not correlate with inflammation markers and patients with positive and negative cultures were similar. C-reactive protein and total white cell count correlated with some components of a disease-specific HRQoL questionnaire. In conclusion, patients with bronchiectasis in a stable phase have raised systemic markers of inflammation. Some markers, particularly the neutrophil count, correlate with disease severity. This result is in keeping with the hypothesis that the level of inflammation determines disease progression and health status.

The influence of decisions made by developers on health status questionnaire content.

To investigate the effect of stringent and lenient criteria upon the process of item selection in the development of a health status questionnaire, an item pool (179 items) was administered to 139 patients with left ventricular dysfunction. Associations between each item and the criteria of gender, age, duration of disease, global health and global impairment were examined. Items were selected from the pool on the basis of their associations with the criteria using four levels of stringency. The most stringent criteria rejected items which had a shared variance of > or = 4% with gender, age and duration of disease and a shared variance of > or = 6% with global health and impairment. The most lenient criteria rejected items which had a shared variance of > or = 6% with gender, age and duration of disease and a shared variance of > or = 4% with global health and impairment. Using the most stringent criteria, 75 items were selected, compared with 127 items using the most lenient criteria. Small differences in the level of association had large effects on item selection. The choice of level of association used to base item selection can have a crucial influence on questionnaire content.

Effect of sputum bacteriology on the quality of life of patients with bronchiectasis.

Bronchiectatic patients have impaired health-related quality of life (QoL) and are prone to chronic lower respiratory tract infections. We have investigated whether impaired QoL is related to sputum bacteriology. Eighty seven patients with non-cystic fibrosis (non-CF) bronchiectasis, in a stable phase of their illness, completed three QoL measures, underwent a computed tomography (CT) scan and lung function tests, and provided a fresh sputum sample for microscopy and culture. The QoL of patients colonized by Pseudomonas aeruginosa (Pa group) was significantly worse than all other patients grouped together (non-Pa group), and specifically those infected by Haemophilus influenzae (Hi group) or who had no bacterial growth (NG group) (p<0.05), but not those infected by other bacterial species (O group). The Pa group had worse lung function, but no significant differences were found between the groups for forced expiratory volume in one second (FEV1) and peak expiratory flow rate. The Pa group had significantly worse bronchiectasis scores than the O, NG and non-Pa groups, but not the Hi group. There were no significant differences between the groups with respect to the number of infective exacerbations in the last year, but the Pa group had significantly more hospital admissions. Patients infected by P. aeruginosa for more than 3 yrs had significantly worse FEV1 (p<0.03) and bronchiectasis scores (p<0.05) than those infected with P. aeruginosa for less time, but not significantly worse QoL. We conclude that, overall, patients infected with P. aeruginosa have worse quality of life, and that P. aeruginosa is associated with a greater extent of disease and worse lung function. Although patients infected with H. influenzae had extensive bronchiectasis their quality of life was better than the P. aeruginosa infected group.

Validation of the St. George's Respiratory Questionnaire in bronchiectasis.

There is no disease-specific instrument available for health status assessment in bronchiectasis. We examined the stability, validity and responsiveness of a measure designed for asthma and COPD, the St. George's Respiratory Questionnaire (SGRQ), in this condition. One hundred and eleven patients were studied on 2 separate d 6 mo apart. On both days each patient completed the SGRQ and measures of general and disease-specific health, mood, and fatigue. They also performed a shuttle walking test and comprehensive lung function tests. Repeatability was tested over 2 wk in 23 patients. The intraclass correlation (ri) for the SGRQ Total score was 0.97. The SGRQ component scores correlated well with relevant markers of disease activity. Examples include: SGRQ Symptoms score versus MRC Wheeze score, r = 0.634, p < 0.0001; Activity score versus shuttle walking test, r = -0.659, p < 0.0001; and impacts score versus physical fatigue, r = 0.610, p < 0.0001. Changes in the SGRQ Total score from entry to follow-up also correlated with changes in other measures of the patients' health. There were significant differences in the SGRQ total score between patients who improved and those who deteriorated over the 6 mo in respect to wheeze (F = 5.6, p < 0.01) and breathlessness (F = 6.05, p < 0.01). We conclude that the SGRQ reflects impaired health in bronchiectasis patients.

Graduate medical education in the United States.

The annual surveys of residency programs on which this report is based have had a higher than 90% response rate for the 5 years previous to 1989. Because of a change to the new electronic data collection system in 1989, the response rate decreased to 78.3%. To adjust for the lower response rate, a regression model computed from data from previous years was developed that permitted projected estimates for 1989 data. These numbers are included in several key tables. The number of GY-1 positions seems to have decreased for 1990, although this may be an artifact of the response rate. Reported unfilled positions, including GY-1 unfilled positions, have increased each year since 1985. The number of new-entry residents (GY-1) seems to be leveling out after decreasing since 1985. Because of the lower response rate, it is difficult to determine the trend in the total number of residents on duty. While the observed number of residents is lower than in 1988, statistical projections indicate an increase of 5% over the 1988 count. Thirty-nine percent of residents were training in family practice, internal medicine, or pediatrics. The number and percent of women in residency programs has remained relatively stable despite a steady increase in the number of women graduating from US medical schools. The percentage of FMG residents has continued to decrease. The percentage of black non-Hispanic residents remains steady. The number of graduates of osteopathic medical schools in ACGME programs has increased 17% since 1987. The number of institutions involved in graduate medical education has not changed significantly during the past 3 years.