EuroQol EQ-5D and condition-specific measures of health outcome in women with urinary incontinence: reliability, validity and responsiveness

Objectives To evaluate the measurement properties of the EuroQoL EQ-5D and two condition-specific patient-reported outcome measures—the Symptom Severity Index (SSI) and the Urinary Incontinence-Specific Quality of Life instrument (I-QoL)—in women with urinary incontinence. Methods A questionnaire comprising all instruments was completed by women taking part in a clinical trial of physiotherapy for urinary incontinence. Follow-up questionnaires were at 6 weeks and 5 months. Data quality, internal consistency reliability, validity and responsiveness were assessed. Results One hundred and seventy-four patients taking part in the clinical trial completed the questionnaire. Instruments had low levels of missing data. The EQ-5D had a large ceiling effect and poor responsiveness. The SSI had poor validity and responsiveness. The I-QoL had levels of reliability that supported application in group assessment, and in some cases, individual assessment, and good evidence of validity. The I-QoL was the most responsive instrument at both 6 weeks and 5 months. Conclusion The I-QoL was the best performing instrument and is recommended as a continence-specific measure of quality of life in a clinical trial setting. The SSI and EQ-5D are not recommended. Alternative generic instruments, which support economic evaluation, require further evaluation in trials of female urinary incontinence. On behalf of the West Midlands Incontinence Research Collaboration.     

Status of patients with first-episode psychosis after one year of phase-specific community-oriented treatment

OBJECTIVE: A phase-specific intervention provided soon after the onset of a first episode of psychosis is likely to engender a more hopeful outlook. This article describes a community-oriented treatment program of phase-specific medical and psychosocial treatments integrated within an intensive case management model for patients with first-episode psychosis in a geographically defined population. One-year status is reported for a consecutive sample of patients with nonaffective mostly schizophrenic first-episode psychosis who were receiving treatment in this program. METHODS: Patients were assessed at baseline and at one year with a modified version of the Interview for Retrospective Assessment of Onset of Schizophrenia, the Structured Clinical Assessment for DSM-IV, the Scale for Assessment of Positive Symptoms, and the Scale for Assessment of Negative Symptoms to ascertain baseline patient characteristics, remission rates, hospital readmission rates, and change in the severity of symptoms. RESULTS: Data at 13 months for 53 patients indicated a complete remission rate of 70 percent, a hospital readmission rate of 20 percent, a highly significant improvement in all dimensions of psychopathology, higher rates of remission among patients who entered treatment within six months of the onset of psychosis (82 percent compared with 60 percent), and a longer median duration of untreated psychosis among patients who did not experience complete remission (10.5 compared with 6.5 months). Nearly half the patients received initial treatment as outpatients without adverse consequences for their subsequent use of hospitalization. CONCLUSIONS: An epidemiologically representative sample of patients experiencing a first episode of psychosis, when treated optimally with low dosages of novel antipsychotics and phase-specific psychological interventions, showed a high rate of clinical recovery and were able to remain in the community most of the time.     

Biomedical assessment and instrumental evaluation of healthy infant skin

The skin forms a critical structural boundary and a perceptual interface for the organism, yet the definition "healthy skin" is surprisingly difficult to describe. The present study's goal was to generate a technical definition of healthy infant skin by quantifying specific biophysical parameters before and after bathing in infants and correlating such parameters to a perceptual maternal evaluation. Fifty-two healthy infants, 3-6 months old, were evaluated before and after freshwater bathing. Diapered skin had a higher transepidermal water loss (TEWL), surface hydration, moisture accumulation rate (MAT), and friction than nondiapered skin before the bath (p < 0.01). Bathing dramatically altered the biophysical properties at both skin sites, with decreased MAT and lower friction, indicating a drier skin surface (p < 0.01). Visual redness and dryness decreased after bathing (p < 0.01). Blinded grading of optical images showed a significant preference for the skin after bathing (p < 0.01). This study provides the first quantitative technical definition of healthy infant skin with positive correlation to perceptual assessment by independent observers (mothers). The findings support the hypothesis that water binding properties of the stratum corneum are altered by occlusion (diapering) and that bathing introduces acute changes in stratum corneum water interactions, leading to a drier skin surface and a preferred skin appearance.     

Hepatitis C virus envelope glycoproteins and potential for vaccine development

HCV envelope glycoproteins play an important role in the initiation of viral infection. The functional dichotomy of the individual HCV glycoproteins was investigated using VSV/HCV pseudotype virus. Surprisingly, VSV/HCV pseudotype virus generated from either E1 or E2 displayed infectivity of a number of mammalian cells. The use of pseudotyped virus has allowed us to better understand the similar and divergent properties of E1 and E2 glycoproteins decorating the envelope of HCV. The serum pseudotype virus neutralizing activity in patient sera did not exhibit a correlation with the infecting HCV genotype or virus load. HCV E2 glycoprotein induces a weak neutralizing antibody response, however the neutralization function was augmented by complement. Taken together, these observations suggest a role for both the glycoproteins in HCV attachment and entry into susceptible host cells. An understanding of HCV entry and strategies appropriate for mimicking cell surface molecules may help in the development of new therapeutic modalities against HCV infection. Furthermore, incorporation of the HCV glycoproteins in a candidate vaccine may offer protection, although additional work is necessary to enhance their immunogenicity.     

Ventricular septal defect complicated by infective endocarditis of the aortic valve causing severe aortic regurgitation: the role of aortic valve repair

BACKGROUND AND AIMS OF THE STUDY: Children with ventricular septal defect (VSD) who develop severe aortic regurgitation following infective endocarditis (IE) require aortic valve replacement in most cases. Few reports exist of repair of the aortic valve under such circumstances. Here, we report details from two patients in whom aortic valve repair resulted in a good outcome. METHODS: Two children (aged 4 and 3 years) with either perimembranous or doubly committed subarterial VSD presented with congestive cardiac failure (NYHA class IV) following IE. The aortic valve in both children, and the pulmonary valve in one child, were severely damaged with vegetation, leading to severe (grade IV) aortic regurgitation. The second patient had bilateral bronchiectasis with respiratory infection and severe anemia. In addition to VSD closure, partial cuspal replacement using glutaraldehyde-tanned pericardium was performed successfully in both cases to restore geometry. RESULTS: Both children showed a dramatic improvement following surgery and during follow up of 36 and 11 months, respectively. Both remained asymptomatic, with good growth, good left ventricular function and the presence of only trivial aortic regurgitation. CONCLUSION: In selected patients with suitable anatomy, repair of the aortic valve with pericardial cusp replacement may be the procedure of choice. An additional benefit is the avoidance of long-term anticoagulation.     

Functional Role of Dendritic Cells in Patients with Unstable Angina

StudiesduringthelastdecadeidentifiedDCinatheroscleroticplaques.Dendriticcellsarepresentintheirimmatureformsinthearterialwallandareactivatedduringatherogenesis[1,2],whichprovidesanewapproachtoexplorethemechanismofT cellactivation[3].Dendriticcellsarefoundinaorticatheroscleroticlesionsinratswithdiet inducedhy percholesterolemia[4]andalsoinapolipoproteinE deficientmice[5].Dendriticcells(DC)wereoriginallydescribedbySteinmanandCohnin1973.Theyarethekeyantigen presentingcellsandarebelievedtoplaya…     

Eradication of spontaneous and experimental adenocarcinoma metastases with chronic indomethacin and intermittent IL-2 therapy

We had earlier shown that tumor-bearing results in an inactivation of IL-2–dependent effector cells by host macrophagederived PGE₂, and that chronic indomethacin therapy (CIT) aimed at blocking prostaglandin synthesis, combined with multiple rounds of IL-2, can cure experimental metastases of a variety of tumors in mice. We have now tested the efficacy of this therapy on spontaneous as well as experimental metastasis of C3–L5 mammary adenocarcinoma in C3H/HeJ mice. Mice transplanted s.c. with C3–L5 cells (and showing visible spontaneous lung metastases between days 7 and 10) were given CIT starting on day 15, plus 2 5–day rounds of IL-2 or IL-2 alone. Mice injected i.v. with 10⁴ C3–L5 cells (and showing lung micrometas-tases on day 5) were placed on CIT on day 5 and given 3 5–day rounds of IL-2 or treated with IL-2 alone. Control mice received vehicles alone. Results revealed that combined CIT + IL-2 therapy in the spontaneous metastasis model caused a regression of primary tumors, a marked reduction in lung metastases scored on days 25–35 and a marked prolongation of host survival (79% cured). Survivors rechallenged with 10⁴ tumor cells i.v. on day 210 resisted tumor growth. In the experimental metastasis model, this therapy also markedly reduced lung metastases and prolonged animal survival (50% cured). In both models, the combination therapy led to the presence of highly active tumoricidal (for C3–L5 and YAC-I lymphoma targets) lymphocytes with AGM-I⁺, Lyt-2^- and Thy-l± phenotype and macrophages in the spleen and the lungs, and ADCC-promoting activity in the serum. CIT + IL-2 therapy can thus effectively eradicate spontaneous and experimental mammary adenocarcinoma metastasis in mice. It activates natural effector cells in situ, generates ADCC-promoting activity in the serum and results in resistance to umor take in this moderately immunogenic tumor model.     

Tuberculous meningitis in children

Summary Ninety cases of tuberculous meningitis have been analysed with special reference to some prognostic factors such as the age of the patient, duration of symptoms before treatment, C.S.F. picture and type of treatment. 78·8 per cent. of cases were males and 84·4 per cent. below the age of 5 years. The peak incidence was below 3 years, 21·1 per cent. of cases occurring below the age of 1 year, the youngest patient being 4 months old. History of contact could be obtained in 27·78 per cent. of cases. X-Ray chest showed evidence of intrathoracic tuberculous foci in 74·4 per cent. of cases, with miliary lesions in 15·5 per cent., hilar lymphadenopathy in 33·3 per cent., bronchopneumonic infiltration in 21·1 per cent., fibrosis in 3·3 per cent. and thickened pleura in 1·1 per cent. of cases. Out of 90 cases, 35 expired, another 35 left the hospital in an unsatisfactory state, and only 20 cases recovered, giving a satisfactory response in 22·2 per cent. of cases. The combined figures for mortality and unsatisfactory results were 82·9 per cent., 77·2 per cent. and 64·3 per cent. between the age groups 0 to 2, 2 to 5 and above 5 years respectively. 84·2 per cent. of cases with coma and/or fits either proved fatal or had severe neurological sequelae. Low cerebrospinal fluid sugar and chlorides and raised proteins affected the prognosis adversely. Treatment under “Category I, II and III” showed satisfactory response in 29·3, 50 and 11·65 per cent. of cases respectively. Steroid therapy did not seem to favourably influence the results in cases picked up at random. From the Department of Pediatrics, Medical College, Amritsar     

Rickets in children (An analysis of forty-two cases)

Summary Forty-two selected cases of rickets, substantiated with radiological evidences, were studied etiologically and clinically with special emphasis on the environment and dietary regime. Forty-one of these came from towns and only one was from rural area. Twenty-four were between 2 to 4 years of age, four being below the age of 2, and the youngest was 6 months old. All these forty-two children belonged to poor socio-economic status and in thirty-three families, the incomeper captia per month ranged from Rs. 5 to Rs. 20. Thirty four were stated to have a daily sun exposure of approximately two to four hours, especially in the winter. The dietary of these children consisted mainly of cereals with hardly any source of protein and calcium. This imbalanced dietary seems to be the most important single factor in the etiology of rickets. Chronic recurrent diarrhoea was found in twenty-seven cases. In fifteen families, there was evidence of rickets in one or other sibs in addition to the patient. Seventeen cases presented with gross deformities of the skeletal system, and fifteen were virtually crippled. Other associated gross nutritional deficiencies were anaemia (thirty-seven cases), wasting (twenty cases), vitamin B deficiency (twelve cases) and vitamin A deficiency (seven cases). From The Department of Pediatrics, Medical College, Amritsar.