Peanut components measured by ISAC: comparison with ImmunoCap and clinical relevance in peanut allergic children.

BACKGROUND: Specific IgE (sIgE) against the peanut component Arachis hypogaea (Ara h) 2 has been shown to be the most important allergen to discriminate between peanut allergy and peanut tolerance. Several studies determined sIgE cut off values for Ara h 2, determined by singleplex measurements. However, cut off values for Ara h 2 from multiplex arrays are less well defined. The aim of this study was to evaluate the correlation between Ara h 2 sIgE determined by singleplex versus multiplex measurements and to assess the diagnostic value of the different peanut components included in Immuno Solid-phase Allergen Chip (ISAC) multiplex analysis in children with a suspected peanut allergy. METHODS: In this retrospective study we analyzed Ara h 2 sIgE values with singleplex Fluorescence Enzyme Immunoassay (FEIA, ImmunoCap) and multiplex microarray (ISAC) measurements in 117 children with a suspected peanut allergy. Also, other peanut components measured by ISAC were analyzed. Double blinded placebo controlled oral food challenges were used as golden standard. RESULTS: Among all studied peanut components FEIA Ara h 2 sIgE showed the highest area under the curve (AUC, 0.922), followed by ISAC Ara h 6 and Ara h 2 sIgE with AUCs of respectively 0.906 and 0.902. Best cut off values to diagnose peanut allergy were 4.40 kU/l for FEIA Ara h 2 sIgE and, 7.43 ISU and 8.13 ISU for respectively Ara h 2 and Ara h 6 sIgE in ISAC microarray. Ara h 2 sIgE determined in FEIA and ISAC showed a good correlation (r = 0.88; p < 0.01). CONCLUSION: Ara h 6 and Ara h 2 sIgE in multiplex ISAC are both good predictors of clinical peanut allergy in Dutch children, and their performance is comparable to the use of Ara h 2 in singleplex FEIA. The simultaneous measurement of different peanut components using ISAC is an advantage and clinically useful to detect peanut allergic children that are Ara h 2 negative but sensitized to other peanut proteins such as Ara h 6.

Use of the Control of Allergic Rhinitis and Asthma Test (CARATkids) in children and adolescents: Validation in Dutch.

BACKGROUND: Allergic rhinitis and asthma are common and closely related diseases. Recently, a Portuguese questionnaire has been developed 'The Control of Allergic Rhinitis and Asthma Test' (CARATkids) that measures disease control of both diseases in children. This study aims to validate the CARATkids in Dutch children and for the first time in adolescents and, in addition, to calculate the minimal clinically important difference (MCID). METHODS: A prospective observational study was conducted in an outpatient clinic. After translation of the CARATkids from Portuguese to Dutch, patients (6-18 years) with asthma or asthma and allergic rhinitis completed the CARATkids, Asthma Control Test, and visual analog scale questionnaire three times. Baseline characteristics, mean scores, internal consistency, test-retest reliability, cross-sectional and longitudinal validity, discriminative properties, responsiveness, and MCID of the CARATkids were assessed. RESULTS: A total of 111 patients were included. In total, 86% and 79%, respectively, completed the questionnaires at the second and third visits. All children had asthma, and 85% had concomitant allergic rhinitis. The internal consistency was good with all expected a priori correlations met. CARATkids scores were higher in patients with uncontrolled asthma and patients with moderate-severe rhinitis compared to better controlled subjects. Patients with a variable asthma control had significantly higher scores during periods of uncontrolled asthma. Also the Guyatt's responsiveness index was good. The MCID was 2.8. CONCLUSIONS: The CARATkids questionnaire is a reliable and valid tool to assess allergic rhinitis and asthma control among Dutch children. The tool can be used in adolescents.

Host biomarkers and paediatric infectious diseases: from molecular profiles to clinical application.

Infectious diseases are an important cause of death among children under the age of 5 (Stein et al., 2004). Most of these deaths are caused by preventable or curable infections. Limited access to medical care, antibiotics, and vaccinations remains a major problem in developing countries. But infectious diseases also continue to be an important public health issue in developed countries. With the help of modern technologies, some infections have been effectively controlled; however, new diseases such as SARS and West Nile virus infections are constantly emerging. In addition, other diseases such as malaria, tuberculosis, and bacterial pneumonia are increasingly resistant to antimicrobial treatment.

Olfactomedin 4 Serves as a Marker for Disease Severity in Pediatric Respiratory Syncytial Virus (RSV) Infection.

BACKGROUND: Respiratory viral infections follow an unpredictable clinical course in young children ranging from a common cold to respiratory failure. The transition from mild to severe disease occurs rapidly and is difficult to predict. The pathophysiology underlying disease severity has remained elusive. There is an urgent need to better understand the immune response in this disease to come up with biomarkers that may aid clinical decision making. METHODS: In a prospective study, flow cytometric and genome-wide gene expression analyses were performed on blood samples of 26 children with a diagnosis of severe, moderate or mild Respiratory Syncytial Virus (RSV) infection. Differentially expressed genes were validated using Q-PCR in a second cohort of 80 children during three consecutive winter seasons. FACS analyses were also performed in the second cohort and on recovery samples of severe cases in the first cohort. RESULTS: Severe RSV infection was associated with a transient but marked decrease in CD4+ T, CD8+ T, and NK cells in peripheral blood. Gene expression analyses in both cohorts identified Olfactomedin4 (OLFM4) as a fully discriminative marker between children with mild and severe RSV infection, giving a PAM cross-validation error of 0%. Patients with an OLFM4 gene expression level above -7.5 were 6 times more likely to develop severe disease, after correction for age at hospitalization and gestational age. CONCLUSION: By combining genome-wide expression profiling of blood cell subsets with clinically well-annotated samples, OLFM4 was identified as a biomarker for severity of pediatric RSV infection.

Evaluating pressure ulcer occurrence in long-term care: pitfalls in interpreting administrative data.

Administrative databases for long-term care frequently collect information on fixed dates of the calendar year, rather than for entire episodes of care. Patients discharged or dying prior to an evaluation date are lost to follow-up. We used one such database, the VA Patient Assessment File, to examine pressure ulcer occurrence in long-term care. Clinical studies have established that most pressure ulcers develop during the first several weeks following admission. In these data, however, pressure ulcer development was less common in patients assessed within 2 months following admission, as compared to those examined at 3 to 6 months. This finding appears to be related to the selective discharge of patients, which makes these patient populations noncomparable. These results highlight that care must be exercised when interpreting results obtained from such administrative data.

Geriatric syndromes as outcome measures of hospital care: can administrative data be used?

OBJECTIVE: To determine how often hospital administrative databases capture the occurrence of two common geriatric syndromes, pressure ulcers and incontinence. DESIGN: Retrospective comparison of a nursing home and hospital database. SETTING: Department of Veterans Affairs (VA) hospitals. PARTICIPANTS: All patients between 1992 and 1996 discharged from VA acute medical care and admitted to a VA nursing home. MEASUREMENTS: The presence of incontinence or a pressure ulcer (stage 2 or larger) on admission to the nursing home was determined. Hospital discharge diagnoses were then reviewed to determine whether these conditions were recorded. The effect of ulcer stage, total number of discharge diagnoses, and temporal trends on the recording of these conditions in discharge diagnoses was also noted. RESULTS: There were 17,004 admissions to nursing homes from acute care in 1996; 12.7% had a pressure ulcer and 43.4% were incontinent. Among these patients with a pressure ulcer, the hospital discharge diagnosis listed an ulcer in 30.8% of cases, and incontinence was included correctly as a discharge diagnosis in 3.4%. While deeper pressure ulcers were more likely to be recorded than superficial ulcers (P < .01), nearly 50% of stage 4 ulcers were not listed among hospital discharge diagnoses. Patients with more discharge diagnoses were more likely to record both conditions correctly. From 1992 to 1996, small but significant (P = .001) improvements were noted in the correct recording of these geriatric syndromes as discharge diagnoses. CONCLUSIONS: The occurrence of pressure ulcers and incontinence cannot be determined from hospital administrative databases and should not be used as outcomes when measuring quality of care among hospitalized patients.

Predictors of pressure ulcer healing among long-term care residents.

OBJECTIVES: To identify predictors of pressure ulcer healing among long-term care residents. DESIGN: A retrospective cohort study. SETTING: Department of Veterans Affairs (VA) long-term care facilities. PARTICIPANTS: All long-term care residents with a pressure ulcer on April 1, 1993, who remained institutionalized as of October 1, 1993. Patients and pressure ulcer status were identified from the Patient Assessment File, a VA administrative database. MEASUREMENTS: Pressure ulcers were considered healed if patients were without an ulcer on October 1, 1993. Predictors of pressure ulcer healing were selected from among patient characteristics in the Patient Assessment File. RESULTS: Pressure ulcers were present in 7.7% of the long-term care residents institutionalized as of April 1, 1993. Among the 819 pressure ulcer patients remaining institutionalized as of October 1, 1993, ulcers had healed in 442 (54.0%). Seventy-two percent of patients with Stage 2 ulcers were ulcer-free at 6 months, compared with 45.2% of patients with Stage 3 ulcers and 30.6% of those with Stage 4 ulcers (P < .001). Significant (P < .05) independent predictors of healing included pressure ulcer size (Odds ratio (OR) = 5.2 for Stage 2 ulcers, OR = 1.5 for Stage 3 ulcers), older age (OR = 1.5), and receiving rehabilitation services (OR = 1.3 for each additional type of therapy). Both immobility (OR = .3) and incontinence (OR = .7) were associated with ulcers not healing. CONCLUSIONS: Most Stage 2 pressure ulcers, and many larger ulcers encountered in long-term care settings will heal. Baseline patient characteristics are important predictors of healing. Interventions may then be targeted at patients whose ulcers are unlikely to heal, and observed facility performance may be compared with expected outcomes.

Pressure ulcer development in the VA: characteristics of nursing homes providing best care.

This study identifies structural characteristics of VA nursing homes that are associated with the best patient outcomes. We evaluated risk-adjusted rates of pressure ulcer development in VA nursing homes and related these rates to facility size, staffing patterns, teaching nursing home status, and rural versus urban locale. Higher rates of pressure ulcer development were seen among urban teaching nursing homes and among nursing homes associated with both larger and smaller VA hospitals. Staffing patterns had a complex association with pressure ulcer development, and smaller nursing home staffs were not clearly associated with higher rates. For multivariate modeling, only hospital size and staffing remained significant independent predictors of pressure ulcer development. These results emphasize that while structural characteristics of VA nursing homes can provide insights about care, improving the quality of care in this setting will require a much greater understanding of how nursing homes are organized to meet patient needs.

Rating long-term care facilities on pressure ulcer development: importance of case-mix adjustment.

OBJECTIVE: To determine the importance of case-mix adjustment in interpreting differences in rates of pressure ulcer development in Department of Veterans Affairs long- term care facilities. DESIGN: A sample assembled from the Patient Assessment File, a Veterans Affairs administrative database, was used to derive predictors of pressure ulcer development; the resulting model was validated in a separate sample. Facility-level rates of pressure ulcer development, both unadjusted and adjusted for case mix using the predictive model, were compared. SETTING: Department of Veterans Affairs long-term care facilities. PATIENTS: The derivation sample consisted of 31 150 intermediate medicine and nursing home residents who were initially free of pressure ulcers and were institutionalized between October 1991 and April 1993. The validation sample consisted of 17 946 residents institutionalized from April 1993 to October 1993. MEASUREMENT: Development of a stage 2 or greater pressure ulcer. RESULTS: 11 factors predicted pressure ulcer development. Validated performance properties of the resulting model were good. Model-predicted rates of pressure ulcer development at individual long-term care facilities varied from 1.9% to 6.3%, and observed rates ranged from 0% to 10.9%. Case-mix-adjusted rates and ranks of facilities differed considerably from unadjusted ratings. For example, among five facilities that were identified as high outliers on the basis of unadjusted rates, two remained as outliers after adjustment for case mix. CONCLUSIONS: Long-term care facilities differ in case mix. Adjustments for case mix result in different judgments about facility performance and should be used when facility incidence rates are compared.

Reducing random variation in reported rates of pressure ulcer development.

OBJECTIVES: The authors evaluated methods of reporting on rates of pressure ulcer development in long-term care to identify approaches that lead to more stable estimates of actual performance. METHODS: Performance measures for facilities that adequately adjust for both random variation and casemix should be relatively stable from one time period to the next. The authors calculated facility rates of pressure ulcer development over eight consecutive time periods and correlated measures over time using different reporting methods including z-scores, combining rates from several time periods, and limiting analyses to large facilities. Results were compared with a Monte Carlo simulation. RESULTS: Observed facility rates of pressure ulcer development varied considerably over time. The average correlation coefficient across seven time comparisons for observed rates was 0.17. Reporting performance as a z-score or limiting the analyses to large facilities increased the correlation. Combining two time periods was effective only when used with one of these other approaches. The correlation coefficient based on a simulation using only large facilities was 0.51. CONCLUSIONS: Random variation affects reported rates of pressure ulcer development. Using only large facilities and combining two time periods limits the effects of random variation and results in more stable estimates of performance. When describing performance, management must consider tradeoffs between having more accurate data, the frequency with which data are provided, and whether it is given to all providers.