Early intervention and disease modification in atopic dermatitis-the current state of the field and barriers to progress.

Atopic dermatitis (AD) is a highly prevalent chronic inflammatory skin disease representing a major source of global disability burden. Disease-modifying therapies are showing promise in chronic inflammatory disorders such as rheumatoid arthritis and Crohn's disease with method and timing of initial treatment impacting long-term disease outcomes. Whether disease-modifying therapies, specifically those used as an early interventional approach, impacts disease course and comorbidity development in AD is not well-understood. We reviewed the progress in disease modification strategies, emphasizing early intervention approaches in common (or proto-typical) inflammatory diseases. Although more common in other fields, disease modification approaches are becoming increasingly investigated in dermatology, though studies in AD are lacking. Despite significant limitations in ongoing and completed studies, early data are promising and suggest that both the choice and timing of early intervention approach can affect long-term disease course and comorbidity development. To best improve AD patient outcomes, more research is needed to further explore the impact of early disease-modifying therapies. Future studies should focus on identifying the most effective approaches and extend the early results to a more inclusive set of comorbidities and longer-term outcomes.

Insulin resistance is associated with increased circulating lipocalin-2 levels in polycystic ovary syndrome: a systematic review and meta-analysis.

INTRODUCTION: This meta-analysis was conducted to compare the circulating lipocalin-2 levels in polycystic ovary syndrome (PCOS). EVIDENCE ACQUISITION: Relevant studies were retrieved by online database and manual searching. The standardized mean differences (SMDs) with 95% confidence intervals (CIs) were obtained by a random-effects meta-analysis. The subgroup analysis based on the Body Mass Index (BMI) and the homeostasis model assessment-estimated insulin resistance (HOMA-IR) was conducted. Meta-analysis of correlations and meta-regression were performed for the associations of lipocalin-2 with the metabolic and hormonal covariates. The funnel plot analysis was used for publication bias. EVIDENCE SYNTHESIS: The combined effect size including a total of 13 studies showed no significant difference in lipocalin-2 levels between PCOS and control groups. However, the subgroup meta-analysis based on insulin resistance showed a significant difference in the circulatory lipocalin-2 levels in PCOS as compared to controls in both HOMA-IR<3 (SMD=-1.15, Z=2.42, P=0.02) and HOMA-IR>3 subgroups (SMD=0.91, Z=2.43, P=0.02). CONCLUSIONS: There were significant associations of lipocalin-2 with age, BMI, estrogen and hyperandrogenism in PCOS. Lipocalin-2 level alterations in PCOS are associated to insulin resistance. More is the insulin resistance, higher is the lipocalin-2 level in PCOS as compared to controls.

Pharmacological effects of D-Pinitol - A comprehensive review.

In recent years, the application of phytochemicals to prevent or treat diseases has received greater attention. These phytochemicals have little or no toxicity against healthy tissues and are thus considered as ideal compounds. An impressive number of modern drugs are obtained from natural sources based on their traditional value. D-Pinitol is a natural compound that is derived from soy and soy products. It is a potentially active molecule that belongs to the class of inositols. D-pinitol has been pharmacologically evaluated for its potent antioxidant, anti-diabetic, anti-inflammatory, anti-cancer, hepatoprotective, cardioprotective, renoprotective, neuroprotective, immunosuppressive, and anti-osteoporotic efficacies. This review is an attempt to validate the plausible pharmacological effects of D-pinitol using various in vivo and in vitro studies. PRACTICAL IMPLICATIONS: The consumption of plant-based products has been significantly increased all over the world. The active phytochemicals that are found in plants are stated to have numerous health promoting functions for the treatment of diabetes, cancer, inflammation, cardiac diseases, liver dysfunction, and many other. D-Pinitol is abundantly present in soybeans that possess notable therapeutic activities. Understanding the effects of D-Pinitol would potentially help in applying this compound in clinical research for the treatment of different disorders.

A Systematic Review and Meta-analysis of Efficacy and Safety of Dexmedetomidine Combined With Intrathecal Bupivacaine Compared to Placebo.

BACKGROUND:  Dexmedetomidine has been approved as a sedative agent in critical patients. It is also frequently used as an adjuvant with local anesthetic in spinal anesthesia. However, its use as an adjuvant has not been approved due to the paucity of data. The present systematic review and meta-analysis were undertaken to synthesize evidence for efficacy and safety when dexmedetomidine is combined with bupivacaine in spinal anesthesia. METHODS: A literature search was done using PubMed, Google Scholar, Embase, and Cochrane Library. Search results were screened and eligible studies were included to perform a systematic review and meta-analysis using the software 'Review Manager (RevMan) version 5.4.1' using a random effect model. Cochrane's' Risk of Bias tool (RoB2)' was used for quality assessment. Mean and standard deviation was used to calculate the standardized mean difference and its forest plot for efficacy measures. For the adverse event, a number of events were used to determine the risk ratio and its forest plot using RevMan software. Publication bias is visualized using a funnel plot. RESULTS:  A total of 21 randomized control trials evaluating the efficacy and safety of intrathecal dexmedetomidine were included in the meta-analysis. A total of 1382 participants was included in this meta-analysis. The effect estimates for efficacy parameters, i.e. duration of the sensory block having SMD 2.33; CI, 1.83-2.83, motor block with SMD 1.83, CI 1.21, 2.46, and analgesia SMD 2.81; CI, 2.11-3.51. The risk ratio for adverse effects, i.e. nausea/vomiting, bradycardia, hypotension was not significant whereas it was significant for the incidence of shivering with RR 0.38; CI 0.23-0.97. The overall risk of bias among included studies was either of 'some concern' or 'high risk.' CONCLUSIONS:  Intrathecal dexmedetomidine when combined with bupivacaine was found to significantly increase the three efficacy parameters, i.e. duration of sensory block, motor block, and analgesia. It also appears to be safe with no increased risk of bradycardia or hypotension. It is also associated with decreased postoperative shivering.

Complementary Metagenomic Approaches Improve Reconstruction of Microbial Diversity in a Forest Soil.

Soil ecosystems harbor diverse microorganisms and yet remain only partially characterized as neither single-cell sequencing nor whole-community sequencing offers a complete picture of these complex communities. Thus, the genetic and metabolic potential of this "uncultivated majority" remains underexplored. To address these challenges, we applied a pooled-cell-sorting-based mini-metagenomics approach and compared the results to bulk metagenomics. Informatic binning of these data produced 200 mini-metagenome assembled genomes (sorted-MAGs) and 29 bulk metagenome assembled genomes (MAGs). The sorted and bulk MAGs increased the known phylogenetic diversity of soil taxa by 7.2% with respect to the Joint Genome Institute IMG/M database and showed clade-specific sequence recruitment patterns across diverse terrestrial soil metagenomes. Additionally, sorted-MAGs expanded the rare biosphere not captured through MAGs from bulk sequences, exemplified through phylogenetic and functional analyses of members of the phylum Bacteroidetes Analysis of 67 Bacteroidetes sorted-MAGs showed conserved patterns of carbon metabolism across four clades. These results indicate that mini-metagenomics enables genome-resolved investigation of predicted metabolism and demonstrates the utility of combining metagenomics methods to tap into the diversity of heterogeneous microbial assemblages.IMPORTANCE Microbial ecologists have historically used cultivation-based approaches as well as amplicon sequencing and shotgun metagenomics to characterize microbial diversity in soil. However, challenges persist in the study of microbial diversity, including the recalcitrance of the majority of microorganisms to laboratory cultivation and limited sequence assembly from highly complex samples. The uncultivated majority thus remains a reservoir of untapped genetic diversity. To address some of the challenges associated with bulk metagenomics as well as low throughput of single-cell genomics, we applied flow cytometry-enabled mini-metagenomics to capture expanded microbial diversity from forest soil and compare it to soil bulk metagenomics. Our resulting data from this pooled-cell sorting approach combined with bulk metagenomics revealed increased phylogenetic diversity through novel soil taxa and rare biosphere members. In-depth analysis of genomes within the highly represented Bacteroidetes phylum provided insights into conserved and clade-specific patterns of carbon metabolism.

Bioimpedance Spectroscopy-Guided Ultrafiltration Normalizes Hydration and Reduces Intradialytic Adverse Events in Hemodialysis Patients.

Chronic fluid overload as well as excessive fluid removal are associated with increased morbidity and mortality in hemodialysis (HD) patients. The clinical method to probe the dry weight is often inaccurate and the bioimpedance spectroscopy (BIS) is shown to improve the accuracy. We compared the impact of BIS and clinical methods to guide ultrafiltration (UF) in a randomized controlled study on the intradialytic complications and blood pressure control in prevalent HD patients. Fifty patients on maintenance HD were randomized to BIS method (BIS-group) and clinical method (CL-group) to guide UF. The body composition monitor (BCM) was done post-HD in all patients at baseline and 2-weeks interval during the study period of 6 months to determine the hydration status, but the result was revealed only to the nephrologist managing the patients in BIS-group to probe the dry weight. The endpoints of the study were blood pressure control, intradialytic complications and anti-hypertensive drug burden. The mean age was 56.0 ± 12.0 years and 70% were male. There was significant increase in patients with normal hydration in BIS-group (20% vs. 88%, p = 0.0001), but remained similar to baseline in CL-group (40% vs. 48%, p = 0.3) at 6 months. The incidence of intradialytic hypotension was significantly reduced in BIS-group (4.84 ± 3.0 vs. 2.8 ± 3.13 events/patient/6 months, p = 0.003). There was 35% reduction in hypertensive pill burden in BIS-group with similar blood pressure, compared to CL-group. Post-dialysis underhydration was more common than over or normal hydration at baseline in our population, indicating that clinical method to probe dry weight often resulted in hypovolemia. BIS method to determine dry weight resulted in normalization in volume status and consequently resulted in significant reduction in intradialytic hypotension and anti-hypertensive pill burden over 6-month period.

Impact of Malnutrition, Inflammation, and Atherosclerosis on the Outcome in Hemodialysis Patients.

Malnutrition, inflammation, and atherosclerosis are significant problems in patients on hemodialysis. A prospective, observational study in 100 hemodialysis patients for 2 years was conducted. The primary outcomes were hospitalizations and mortality at the end of 2 years. The mean age was 61 ± 11.3 years and 69% were male. Seven patients did not complete the study (five underwent transplant and two were shifted to other units). Serum albumin was significantly lower in malnourished patients at 6 months from the beginning of the study period (3.58 vs. 3.79 g/dl, P = 0.001). Malnutrition based on subjective global assessment (SGA) was seen in 30 (32%) patients: mild to moderate in 27 (29%) and severe in 3 (3%). Inflammation was seen in 73 (78.5%) patients and intimal-medial thickness of >1.1 mm indicating significant atherosclerosis was seen in 73 (78.5%) patients. Modified SGA score and malnutrition-inflammation score (MIS) were significantly more in the malnourished group. Statistically significant association was seen between hospitalization and mortality in the malnourished population, and the odds ratio of death in malnourished patients was 9.83 (95% confidence interval: 2.8-34.3, P < 0.001). There was a moderate correlation between malnutrition assessed by modified SGA and MIS score (r = 0.54, P < 0.001). Mortality rate was 37% in patients with mild to moderate and 67% in severe malnutrition. Hospital admission was seen in 43 (46%) patients and was significantly more common in malnourished compared to well-nourished patients (77% vs. 32%, P < 0.001). Multiple logistic regression analysis showed that malnutrition by Modified SGA was the only significant variable associated with mortality at 2 years, and addition of MIS score did not improve the predictive ability of the model to modified SGA. We recommend the use of modified SGA and serial serum albumin to monitor nutrition in hemodialysis patients.

A pilot randomized study comparing extralevator with conventional abdominoperineal excision for low rectal cancer after neoadjuvant chemoradiation.

AIM: The aims of this study were to assess the feasibility of performing an extralevator abdominoperineal excision (ELAPE) after neoadjuvant chemoradiation (NCRT), to compare the rates of circumferential resection margin (CRM) involvement and intra-operative perforation (IOP) of the specimen, and to assess the amount of tissue removed around the muscularis propria (MP)/internal sphincter (IS) of the lower rectum in patients with low rectal cancer undergoing ELAPE compared with conventional abdominoperineal excision (CAPE) after NCRT. METHOD: This was an open-label, parallel-arm pilot randomized trial conducted in India. Twenty patients were randomized to one of the study arms. The surgical specimens were fixed, serially cross-sectioned and photographed. Using specialized morphometry software, the amount of tissue resected with each operation was measured. RESULTS: There was a nonsignificant trend towards more IOPs (30% vs 0%, P = 0.06) and a higher CRM involvement rate (40% vs 20%, P = 0.32) in the CAPE arm. ELAPE removed a significantly greater amount of tissue around the IS/MP when compared with CAPE (mean ± SD: 1911.39 ± 382 mm2 vs 1132.03 ± 371 mm2 , P < 0.001). The mean distance from the IS/MP to the CRM was significantly greater in the ELAPE arm both in the posterior (mean ± SD: 28.28 ± 3 mm vs 9.63 ± 3 mm, P < 0.001) and lateral (mean ± SD: 13.69 ± 3 mm vs 9.72 ± 3 mm, P = 0.009) parts of the rectum but not in the anterior part (mean ± SD: 6.74 ± 2 mm vs 6.10 ± 4 mm, P = 0.64). The short-term morbidity was not significantly different between the two procedures. CONCLUSION: ELAPE removed more tissue in the lower rectum and resulted in a lower rate of IOP and CRM involvement when compared with CAPE, even after NCRT.

Clinical utility of urine neutrophil gelatinase-associated lipocalin measured at admission to predict outcomes in heterogeneous population of critically ill patients.

Urine neutrophil gelatinase-associated lipocalin (uNGAL) is a reliable early biomarker of acute kidney injury (AKI) in a homogeneous patient population. However, its utility in a heterogeneous population of critically ill, in whom the time of onset of renal insult is often unclear, is not clearly established. We evaluated the ability of a single measurement of uNGAL in a heterogeneous adult population, on admission to intensive care unit (ICU), to predict the occurrence of AKI and hospital mortality. One hundred and two consecutive adult patients had uNGAL measured within 8 h of admission to ICU. The demographic and laboratory data were collected at admission. The diagnosis of AKI was based on AKI Network (AKIN) criteria. The primary outcome was the development of AKI, and the secondary outcome was hospital mortality. The mean age was 54 ± 16.4 years and 65% were males. Urine NGAL (ng/ml) was 69 ± 42 in patients with AKI (n = 42) and 30.4 ± 41.7 in those without AKI (P < 0.001). The area under the receiver operating characteristic (ROC) curve for prediction of AKI was 0.79 and for serum creatinine (SCr) was 0.88. The sensitivity and specificity for a cut-off value of uNGAL of 75 ng/ml to predict AKI were 0.5 and 0.85 respectively. uNGAL > 75 ng/ml was a strong (odd ratio = 5.17, 95% confidence interval: 1.39-19.3) and independent predictor of hospital mortality. A single measurement of uNGAL at admission to ICU exhibited good predictive ability for AKI though the sensitivity was low. The predictive ability of uNGAL was inferior to simultaneously measured SCr at admission, hence limited its clinical utility to predict AKI. However, admission uNGAL was a strong, independent predictor of hospital mortality.

Robotic pancreaticoduodenectomy: comparison of complications and cost to the open approach.

BACKGROUND: Robotic pancreaticoduodenectomy (RP) has shown some advantages over open pancreaticoduodenectomy (OP) but no data has been published providing a cost comparison. METHODS: Retrospective analysis of all pancreaticoduodenectomies at a single quaternary cancer referral center was performed. Patient demographics, comorbidities, operative characteristics, complications, and charge data were recorded, and then compared using standard statistical methods. RESULTS: 71 pancreaticoduodenectomies were performed: 22 RP and 49 OP. Patients undergoing OP had similar demographics, comorbidities, pathology, and oncologic characteristics as patients undergoing RP. While operative charges were higher for RP, once inpatient stay associated costs and follow-up costs were included, there was no difference in total costs between RP and OP. CONCLUSIONS: Patients undergoing RP have equivalent rates of R0 resection as OP, and benefit from decreased number of complications, surgical site infections, and length of stay in the intensive care unit. Once cost of complications and follow-up are incorporated, no significant difference between procedures exists. Copyright © 2015 John Wiley & Sons, Ltd.

Accuracy of spot urine protein creatinine ratio in measuring proteinuria in chronic kidney disease stage 3 and 4.

We studied the accuracy of spot urine protein creatinine ratio (SpUr-PCR) to assess 24 h urine protein excretion (24 h-UP) in patients with chronic kidney disease (CKD). A total of 100 proteinuric CKD patients of stages 3 and 4 were studied. 24 h urine was collected to measure 24 h-UP and creatinine. A random day time urine sample was analyzed to measure the PCR. A formula to estimate 24 h creatinine excretion was derived from linear regression analysis and a correction factor was introduced to assess whether this improves the accuracy of the SpUr PCR in predicting 24 h-UP. Accuracy of the SpUr-PCR was assessed by Pearson's correlation, regression analysis, and Bland Altman analysis. Mean age was 51.85 ± 12 years and 81% of the patients were male. SpUr-PCR predicted 24 h-UP with good accuracy (r = 0.86 on a data transformed to a logarithmic scale, P < 0.001) and there was a good agreement between these two measures of proteinuria. However, SpUr-PCR was inaccurate in the subgroup with nephrotic range proteinuria (r = 0.35, P = 0.062), but when a correction factor for 24-h urine creatinine (24 h-UCr) was introduced, the accuracy of SpUr-PCR improved significantly in this group (r = 0.45, P = 0.013). Introduction of the correction factor improved the degree of agreement between these two measures in women, but not the correlation. Overall, SpUr-PCR accurately predicted 24 h-UP. Adding a correction factor for 24 h-UCr improved correlation in the subgroup of patients with the nephrotic range proteinuria and the degree of agreement in female patients, and hence may be used in expressing proteinuria measured by SpUr-PCR to improve its accuracy in them.

Retarding the progression of chronic kidney disease with renin angiotensin system blockade.

We assessed the effect of renin angiotensin system blockade (RASB) in chronic kidney disease (CKD) of diverse etiology. Two hundred and sixty-five consecutive CKD patients attending our renal clinic, with estimated glomerular filtration rate (eGFR) of 20-70 ml/min/1.73m(2) at baseline and a minimal follow-up of 1 year, were studied retrospectively. We devised a scoring system to quantify RASB, wherein the maximum dose of an agent recommended for control of hypertension was scored as 1. The renal endpoints studied were the rate of change in eGFR (ΔeGFR) and decline of eGFR>50%. The mean age was 48 ± 11.2 years and 69% were male. The mean duration of follow-up was 4 ± 2.7 years. The rate of ΔeGFR was -1.5 ± 5.0 ml/min/1.73 m(2) per year in patients who received RASB (N=168) and -6.0 ± 5.4 in those who did not (N=97) (P<0.001). The incidence of decline of eGFR >50% was 11.3% with RASB and 24.7% without (P=0.003). In a subgroup of patients who received RASB, the incidence of decline of eGFR >50% was 17.8% in the low-dose RASB group (N=84, RASB score 0.63 ± 0.38) and 4.8% in the high-dose group (N=84, RASB score 2.5 ± 0.7) (P=0.001). RASB was associated with significantly better renoprotection in CKD of diverse etiology, even in nonproteinuric diseases. This effect appeared to be dose-dependent, with higher supramaximal doses exhibiting better renoprotection than the lower conventional doses. Our results make a strong case for use of aggressive RASB in all CKD patients to postpone end-stage renal disease.

Rh2O3 versus IrO2: relativistic effects and the stability of Ir4+.

Despite the wide-ranging applications of binary Rh and Ir oxides, their stability and trends in Rh and Ir oxidation states are not fully understood. Using first-principles electronic structure calculations, we demonstrate that the origin of the categorical stability of Ir(4+) is the relativistic contraction of the 6s orbital and, consequently, an expansion of 5d orbitals. Relativistic effects significantly stabilize Ir(4+)-containing metallic rutile IrO(2) over a wide range of O chemical potentials, despite the choice that Ir has of forming semiconducting corundum Ir(2)O(3). In contrast, Rh is found to display a wider stability range for corundum Rh(2)O(3) with Rh(3+) and a greater propensity for multiple oxidation states.

Complete and draft genome sequences of six members of the Aquificales.

The Aquificales are widespread in marine and terrestrial hydrothermal environments. Here, we report the complete and draft genome sequences of six new members of the Aquificales: two marine species, Persephonella marina strain EX-H1 and Hydrogenivirga strain 128-5-R1 (from the East Pacific Rise, 9 degrees 50.3'N, 104 degrees 17.5'W, and the Eastern Lau Spreading Center, 176 degrees 11.5'W, 20 degrees 45.8'S, respectively), and four terrestrial isolates, Sulfurihydrogenibium azorense strain Az-Fu1, Sulfurihydrogenibium yellowstonense strain SS-5, and Sulfurihydrogenibium strain Y03AOP1 (from Furnas, Azores, Portugal, and Calcite Springs and Obsidian Pool in Yellowstone National Park, United States, respectively), and the only thermoacidophilic isolate, Hydrogenobaculum strain Y04AAS1 (from a stream adjacent to Obsidian Pool). Significant differences among the different species exist that include nitrogen metabolism, hydrogen utilization, chemotaxis, and signal transduction, providing insights into their ecological niche adaptations.

Seasonal variation in the presentation of abdominal pain.

BACKGROUND: Anxiety and depression, conditions frequently associated with childhood chronic abdominal pain (AP), are characterized by seasonal exacerbations. A seasonal pattern characterized by a higher frequency of consultations for AP during winter has been suspected but has never, to our knowledge, been demonstrated. We hypothesize the presence of a seasonal variation in AP consultations with a winter predominance. AIMS: To determine the seasonal distribution of AP consultations among centers across time and geographic latitude. PATIENTS AND METHODS: This was a retrospective cohort study. The number of outpatient consultations from primary care clinics and every pediatric specialty clinic that resulted in a diagnosis of AP and the total number of outpatient consultations (2001-2004) from 6 tertiary care institutions (Chicago, Pittsburgh, Wilmington, Pensacola, Orlando, Jacksonville) was determined. Rates of consultations were compared across time and between cities. Four time periods of interest, with 2- and 3-month definitions, were arbitrarily selected. Seasonal rates across time were compared separately for each of the 2-month (January-February vs June-July) and 3-month periods (January-March vs June-August). Logistic regression models for each city were used to determine variations in the rate of outpatient AP cases by season or by year. RESULTS: A total of 3,929,522 outpatient consultations and 73,591 AP consultations were analyzed. The rates of AP consultations were consistently higher in the winter months at all of the sites. The results differed between sites at northern and southern latitudes. CONCLUSIONS: There seems to be a seasonal variation in consultation patterns for AP at the tertiary care level. A possible role of daylight hours, climate, latitude, and stress is proposed.

Case-control study of risk factors for the development of post-transplant lymphoproliferative disease in a pediatric heart transplant cohort.

PTLD is an important complication following heart transplantation. To better define the risk factors of PTLD in children, we performed a case-control study. All pediatric cardiac transplant recipients who developed their first episode of PTLD were matched by age (+/-1 yr) and time since transplant (+/-1 yr) with those who did not. PTLD occurred in nine of 95 cardiac transplant recipients (9%), 0.3-7.8 yr following cardiac transplantation (median = 2.5 yr). Patients were 0.1-16.4 yr (median = 3.7) at transplantation. Biopsies revealed polymorphic B cell hyperplasia (three), polymorphic B cell lymphoma (one), monomorphic diffuse large cell B cell lymphoma (three) and monomorphic Burkitt's-like lymphoma (two). Patients who developed PTLD were at no greater risk of death (p = 0.31). Recipient EBV seronegativity at time of transplant (p = 0.08), EBV seroconversion (p = 0.013) and recipient CMV seronegativity (p = 0.015) were associated with the development of PTLD by conditional logistic regression; sex, race, donor age, recipient diagnosis, donor CMV seropositivity, recipient treatment for CMV infection, EBV seropositivity at the time of PTLD diagnosis, and number of rejection episodes, treated rejection episodes, and lympholytics used were not. There was no significant association between PTLD and death in our recipients. EBV seroconversion and recipient CMV seronegativity were associated with the development of PTLD.

Weight loss and reduced body mass index: a critical issue in children with multiorgan chronic graft-versus-host disease.

Weight loss and malnutrition are major problems in patients with chronic graft-versus-host disease (GVHD). In adults, low body mass index (BMI) is a predictor for mortality; however, weight loss and BMI have not been studied in pediatric chronic GVHD. A retrospective study on 18 children with extensive chronic GVHD was completed. Median age at SCT was 12.3 (range 0.6-23) years; age at chronic GVHD diagnosis was 12.5 (1-23) years. Patients with multiorgan involvement had a mean maximal decrease in BMI of 20.9% and most dropped below 10th percentile in expected weight-for-age. This change in BMI not only indicates a significant decrease in weight but often a plateau in stature. In contrast, patients with one organ system involved had a mean maximal decrease in BMI of 5% and did not fall below 10th percentile. All patients with multiorgan involvement required salvage therapy beyond steroids and CSA. Three patients died due to complications of chronic GVHD. Weight loss and malnutrition (as reflected by a decrease in BMI) are clinically significant issues in children with multisystem chronic GVHD. Weight loss is likely another systemic manifestation of the disease and may contribute, along with other factors such as increased immunosuppression and infection, to increased mortality in this group.

Why generic and disease-specific quality-of-life instruments should be used together for the evaluation of patients with persistent allergic rhinitis.

BACKGROUND: The importance of assessing health-related quality of life (HRQL) of patients with allergic rhinitis (AR) has been well established, but the specific roles of rhinitis-specific or general health instruments have not been delineated. OBJECTIVE: We analysed the psychometric properties of a disease-specific instrument, the Rhinoconjunctivitis Quality-of-Life Questionnaire (RQLQ) and the general health instrument, the Medical Outcome Short-Form 36 (SF-36) as they are employed in combination in patients with persistent AR in clinical practice. METHOD: We analysed the data collected from a prospective study of 43 newly diagnosed patients with persistent AR and 44 controls. We interviewed the patients four times, at baseline, weeks 4, 8 and 10. RESULTS: The RQLQ and SF-36 have good discriminative property, internal consistency, and test-retest reliability. The RQLQ is superior to the SF-36 as an evaluative instrument because more of its domains respond to change, the magnitude of change was greater, and the response was faster. The SF-36 is more susceptible to floor and ceiling effects. Both instruments are unsuitable for mildly symptomatic patients based on Rasch model analysis. Each questionnaire assesses a distinct and significant portion of the total HRQL of persistent AR. CONCLUSION: The SF-36 and RQLQ are good for discriminating rhinitis patients from controls, but the former is poor for detecting changes in QOL. Both are inappropriate for mildly symptomatic patients. Each instrument measures non-overlapping halves of the measurable HRQL. For an assessment of the HRQL in persistent AR that is complete and responsive both instruments should be employed together.