Validation of the Cutaneous Dermatomyositis Disease Area and Severity Index: characterizing disease severity and assessing responsiveness to clinical change.

BACKGROUND: The Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) was developed for use in clinical trials and longitudinal patient assessment. OBJECTIVES: To characterize disease severity using the CDASI and assess the responsiveness of this instrument to clinically meaningful changes in disease activity. METHODS: Patients with cutaneous dermatomyositis at the University of Pennsylvania (UPenn, n = 93) and Stanford University (Stanford, n = 106) were prospectively evaluated using the CDASI, physician global assessment (PGA) Likert scales and a visual analogue scale (VAS). Data was analysed using logistic regression models and receiver operating characteristic curves to select cut-offs. RESULTS: Baseline CDASI activity scores for the patients evaluated at UPenn ranged from 0 to 47 (median 17), and baseline PGA VAS scores ranged from 0 to 9·6 (median 1·1). At UPenn a CDASI activity score of 19 differentiated mild from moderate and severe disease. At Stanford baseline CDASI scores ranged from 0 to 48 (median 21), baseline PGA VAS scores ranged from 0 to 9·7 (median 4·2) and CDASI activity scores of 14 or less characterized mild disease. When a 2-cm change in the PGA VAS was regarded as a clinically significant improvement, a 4-point (UPenn) or 5-point (Stanford) change in CDASI reflected a minimal clinically significant response. CONCLUSIONS: The CDASI is a valid and responsive measure that can be used to characterize cutaneous dermatomyositis severity and detect improvement in disease activity. Variations in cut-offs may be due to differences in disease severity between the two populations or inter-rater variations in the use of the external gold measures.

The impact of skin damage due to cutaneous lupus on quality of life.

BACKGROUND: Patients with more severe cutaneous lupus erythematosus (CLE) have a poorer quality of life (QoL). Racial and ethnic disparities have been reported in disease activity and outcomes in systemic lupus erythematosus, but similar information is not available for CLE. OBJECTIVES: To evaluate the impact of lupus-related skin damage on skin-specific QoL, and to analyse differences stratified by ethnic background. METHODS: Data collected included sex, race, diagnosis and Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and Skindex-29 scores. These parameters were analysed at the initial and last visits. CLASI damage scores (dyspigmentation and scarring) and activity scores were collected, grouped by ethnicity, and correlated with Skindex-29. Overall, 223 patients were analysed at baseline, with 141 completing more than one study visit. RESULTS: The majority of patients were white (63·7%), followed by African American (29·1%) and Asian American (4·0%). African American patients accounted for a disproportionate percentage of both localized (50%) and generalized discoid lupus erythematosus (DLE) (49%). Median CLASI damage scores differed significantly between the African American, white and Asian American patients, at both the first (8·5, 4·0, 7·0, respectively; P < 0·0001) and last visit (10·0, 6·0, 8·5, respectively; P < 0·01). CLASI damage scores in African Americans correlated with CLASI activity scores (Spearman r = 0·45, P = 0·0003). CONCLUSIONS: There was no significant correlation between CLASI damage scores and Skindex domains overall. Individually, dyspigmentation and scarring also did not have a significant effect on QoL. Ethnic differences in patients with CLE were found: African American patients exhibited a high rate of DLE and experienced damage early in their disease course, frequently in conjunction with disease activity.

Physicians' perspectives on the uncertainties and implications of chromosomal microarray testing of children and families.

Chromosomal microarray analysis (CMA) has improved the diagnostic rate of genomic disorders in pediatric populations, but can produce uncertain and unexpected findings. This article explores clinicians' perspectives and identifies challenges in effectively interpreting results and communicating with families about CMA. Responses to an online survey were obtained from 40 clinicians who had ordered CMA. Content included practice characteristics and perceptions, and queries about a hypothetical case involving uncertain and incidental findings. Data were analyzed using nonparametric statistical tests. Clinicians' comfort levels differed significantly for explaining uncertain, abnormal, and normal CMA results, with lowest levels for uncertain results. Despite clinical guidelines recommending informed consent, many clinicians did not consider it pertinent to discuss the potential for CMA to reveal information concerning biological parentage or predisposition to late-onset disease, in a hypothetical case. Many non-genetics professionals ordering CMA did not feel equipped to interpret the results for patients, and articulated needs for education and access to genetics professionals. This exploratory study highlights key challenges in the practice of genomic medicine, and identifies needs for education, disseminated practice guidelines, and access to genetics professionals, especially when dealing with uncertain or unexpected findings.

Randomized multicenter clinical trial of myofascial physical therapy in women with interstitial cystitis/painful bladder syndrome and pelvic floor tenderness.

PURPOSE: We determined the efficacy and safety of pelvic floor myofascial physical therapy compared to global therapeutic massage in women with newly symptomatic interstitial cystitis/painful bladder syndrome. MATERIALS AND METHODS: A randomized controlled trial of 10 scheduled treatments of myofascial physical therapy vs global therapeutic massage was performed at 11 clinical centers in North America. We recruited women with interstitial cystitis/painful bladder syndrome with demonstrable pelvic floor tenderness on physical examination and a limitation of no more than 3 years' symptom duration. The primary outcome was the proportion of responders defined as moderately improved or markedly improved in overall symptoms compared to baseline on a 7-point global response assessment scale. Secondary outcomes included ratings for pain, urgency and frequency, the O'Leary-Sant IC Symptom and Problem Index, and reports of adverse events. We compared response rates between treatment arms using the exact conditional version of the Mantel-Haenszel test to control for clustering by clinical center. For secondary efficacy outcomes cross-sectional descriptive statistics and changes from baseline were calculated. RESULTS: A total of 81 women randomized to the 2 treatment groups had similar symptoms at baseline. The global response assessment response rate was 26% in the global therapeutic massage group and 59% in the myofascial physical therapy group (p=0.0012). Pain, urgency and frequency ratings, and O'Leary-Sant IC Symptom and Problem Index decreased in both groups during followup, and were not significantly different between the groups. Pain was the most common adverse event, occurring at similar rates in both groups. No serious adverse events were reported. CONCLUSIONS: A significantly higher proportion of women with interstitial cystitis/painful bladder syndrome responded to treatment with myofascial physical therapy than to global therapeutic massage. Myofascial physical therapy may be a beneficial therapy in women with this syndrome.

Comparative impact on prostanoid biosynthesis of celecoxib and the novel nonsteroidal anti-inflammatory drug CG100649.

Nonsteroidal anti-inflammatory drugs (NSAIDs) elevate cardiovascular risk by disrupting cyclooxygenase-2 (COX-2)-dependent biosynthesis of prostacyclin (PGI(2)). CG100649 is a novel NSAID proposed to inhibit both COX-2 and carbonic anhydrase (CA)-I/-II. We compared its impact on prostanoid biosynthesis with that of celecoxib, an NSAID purposefully designed to selectively inhibit COX-2. In a controlled, double-blind randomized trial, single oral doses of 2 or 8 mg CG100649, 200 mg celecoxib, or placebo were well tolerated by healthy volunteers (n = 23). Both CG100649 and celecoxib had the effect of depressing urinary excretion of 2,3-dinor-6-keto-PGF(1α) (PGI-M); the effect of CG100649 was dose-dependent and more sustained (up to 240 h after the dose) than that of celecoxib. Neither CG100649 nor celecoxib significantly inhibited COX-1-dependent prostanoid formation. CA inhibition was not detected after administration of CG100649, despite its partitioning asymmetrically into erythrocytes. CG100649 and celecoxib are both relatively selective inhibitors of COX-2, but they differ in duration of action. Whether they have similar impact on cardiovascular events remains to be determined.

The HIT Expert Probability (HEP) Score: a novel pre-test probability model for heparin-induced thrombocytopenia based on broad expert opinion.

BACKGROUND: The diagnosis of heparin-induced thrombocytopenia (HIT) is challenging. Over-diagnosis and over-treatment are common. OBJECTIVES: To develop a pre-test clinical scoring model for HIT based on broad expert opinion that may be useful in guiding clinical decisions regarding therapy. PATIENTS/METHODS: A pre-test model, the HIT Expert Probability (HEP) Score, was constructed based on the opinions of 26 HIT experts. Fifty patients referred to a reference laboratory for HIT testing comprised the validation cohort. Two hematology trainees scored each patient using the HEP Score and a previously published clinical scoring system (4 T's). A panel of three independent experts adjudicated the 50 patients and rendered a diagnosis of HIT likely or unlikely. All subjects underwent HIT laboratory testing with a polyspecific HIT ELISA and serotonin release assay (SRA). RESULTS: The HEP Score exhibited significantly greater interobserver agreement [intraclass correlation coefficient: 0.88 (95% CI 0.80-0.93) vs. 0.71 (0.54-0.83)], correlation with the results of HIT laboratory testing and concordance with the diagnosis of the expert panel (area under receiver-operating curve: 0.91 vs. 0.74, P = 0.017) than the 4 T's. The model was 100% sensitive and 60% specific for determining the presence of HIT as defined by the expert panel and would have allowed for a 41% reduction in the number of patients receiving a direct thrombin inhibitor (DTI). CONCLUSION: The HEP Score is the first pre-test clinical scoring model for HIT based on broad expert opinion, exhibited favorable operating characteristics and may permit clinicians to confidently reduce use of alternative anticoagulants. Prospective multicenter validation is warranted.

Responsiveness of the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI).

OBJECTIVES: The NIH-Chronic Prostatitis Symptom Index (NIH-CPSI) was developed to assess symptoms and quality of life in men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). We assessed the responsiveness of the NIH-CPSI to change over time and defined thresholds for changes perceptible to patients. METHODS: We studied 174 men with CP/CPPS who participated in a placebo-controlled randomized clinical trial. Changes from baseline to six weeks in the NIH-CPSI total score and pain, urinary, and quality of life subscores were compared to a global response assessment (GRA). Effect sizes and Guyatt statistics were calculated to evaluate responsiveness; 95% confidence intervals were produced using bootstrapping. RESULTS: All scores decreased over time with the largest decrease in subjects who reported on the GRA that they were markedly improved. The NIH-CPSI total, pain, and quality of life scores were highly responsive in the improved groups; the urinary score showed minimal responsiveness. There was no evidence of responsiveness among those subjects who worsened on the trial. ROC curves identified a 6-point decline in the NIH-CPSI total score as the optimal threshold to predict treatment response. CONCLUSIONS: The NIH-CPSI total score and pain and quality of life subscores are responsive to change over time.

Responsiveness of symptom scales for interstitial cystitis.

OBJECTIVES: To evaluate the responsiveness of composite scales to change over time in a clinical trial of patients with interstitial cystitis (IC). The measurement of symptoms in IC includes the O'Leary-Sant Symptom and Problem Indexes and the University of Wisconsin Interstitial Cystitis Inventory and scales that measure the individual symptom domains of pain/discomfort, urgency, and voiding frequency. METHODS: The data were derived from a randomized clinical trial conducted by the Interstitial Cystitis Clinical Trials Group. Participants met the National Institutes of Health-National Institute for Diabetes, and Digestive and Kidney Diseases criteria for IC and reported at least moderate pain and frequency. The primary endpoint was a patient-reported global response assessment (GRA) at 24 weeks. Secondary endpoints included the three composite indexes, pain/discomfort and urgency, and 24-hour frequency. Responsiveness was assessed by comparing symptom score changes against response categories defined by the GRA. RESULTS: Of the 121 subjects in the original trial, 94 with complete data were included. All three composite indexes were sensitive to subject improvement over time as measured by the GRA. A 1.2-point change in the O'Leary-Sant indexes and a 3.1-point change in the Wisconsin IC inventory corresponded to a one-category change in the GRA. Individual symptoms were also responsive. The correlation was high among the changes in the six outcome measures. CONCLUSIONS: The three composite symptom scales are responsive to change over time in patients with IC. These indexes provide important insight into symptom changes and are recommended as secondary endpoints in future clinical trials of IC. Additional endpoints addressing individual symptom domains should also be considered to aid in the evaluation of effect mechanisms.

A pilot clinical trial of oral pentosan polysulfate and oral hydroxyzine in patients with interstitial cystitis.

PURPOSE: This pilot study was designed to evaluate the feasibility of a multicenter, randomized, clinical trial in interstitial cystitis (IC). Secondary objectives were to evaluate the safety and efficacy of oral pentosan polysulfate sodium (PPS), hydroxyzine, and the combination to consider their use in a larger randomized clinical trial. MATERIALS AND METHODS: A 2 x 2 factorial study design was used to evaluate PPS and hydroxyzine. Participants met the National Institutes of Health-National Institute for Diabetes and Digestive and Kidney Diseases criteria for IC and reported at least moderate pain and frequency for a minimum of 6 months before study entry. The primary end point was a patient reported global response assessment. Secondary end points included validated symptom indexes and patient reports of pain, urgency and frequency. The target sample size was 136 participants recruited during 10 months. RESULTS: A total of 121 (89% of goal) participants were randomized over 18 months and 79% provided complete followup data. The response rate for hydroxyzine was 31% for those treated and 20% for those not treated (p = 0.26). A nonsignificant trend was seen in the PPS treatment groups (34%) as compared to no PPS (18%, p = 0.064). There were no treatment differences for any of the secondary end points. Adverse events were mostly minor and similar to those in previous reports. CONCLUSIONS: The low global response rates for PPS and hydroxyzine suggest that neither provided benefit for the majority of patients with IC. This trial demonstrated the feasibility of conducting a multicenter randomized clinical trial in IC using uniform procedures and outcomes. However, slow recruitment underscored the difficulties of evaluating commonly available IC drugs.

Group sequential methods and sample size savings in biomarker-disease association studies.

Molecular epidemiological association studies use valuable biosamples and incur costs. Statistical methods for early genotyping termination may conserve biosamples and costs. Group sequential methods (GSM) allow early termination of studies on the basis of interim comparisons. Simulation studies evaluated the application of GSM using data from a case-control study of GST genotypes and prostate cancer. Group sequential boundaries (GSB) were defined in the EAST-2000 software and were evaluated for study termination when early evidence suggested that the null hypothesis of no association between genotype and disease was unlikely to be rejected. Early termination of GSTM1 genotyping, which demonstrated no association with prostate cancer, occurred in >90% of the simulated studies. On average, 36.4% of biosamples were saved from unnecessary genotyping. In contrast, for GSTT1, which demonstrated a positive association, inappropriate termination occurred in only 6.6%. GSM may provide significant cost and sample savings in molecular epidemiology studies.

Do persons with dementia vote?

To examine whether patients with dementia voted in the 2000 US Presidential Election, the authors surveyed 75 caregivers of patients with dementia. A substantial portion of patients with mild to moderate dementia voted on their own at a voting booth. Patients cared for by spouses were more likely to vote than patients cared for by adult children. Further research is needed to understand how persons with dementia and their caregivers decide what activities the person can and cannot continue and how well these decisions correspond to measures of competency.

Systemic IFN-beta gene therapy results in long-term survival in mice with established colorectal liver metastases.

Most patients succumbing to colorectal cancer fail with liver-predominant metastases. To make a clinical impact in this disease, a systemic or whole-liver therapy may be required, whereas most cancer gene therapy approaches are limited in their ability to treat beyond local disease. As a preclinical model for cancer gene therapy, recombinant adenovirus containing the human IFN-beta (hIFN-beta) cDNA was delivered systemically in nude mouse xenograft models of human colorectal cancer liver metastases. The vector targeted hepatocytes that produced high levels of hIFN-beta in the liver, resulting in a profound apoptotic response in the tumors and significant tumor regression. hIFN-beta gene therapy not only resulted in improved survival and long-term cure in a micrometastatic model, but provided similar benefits in a clinically relevant gross disease model. A similar recombinant adenovirus containing the murine IFN-beta (mIFN-beta) cDNA also resulted in a therapeutic response and improved survival in syngeneic mouse models of colorectal cancer liver metastases. Depletion studies demonstrate a contribution of natural killer cells to this therapeutic response. The toxicity of an adenoviral vector expressing murine IFN-beta in a syngeneic model is also presented. These encouraging results warrant further investigation of the use of cancer gene therapy for targeting metastatic disease.

Inclusion of the herpes simplex thymidine kinase gene in a replicating adenovirus does not augment antitumor efficacy.

Replication-incompetent adenoviruses (Ad) carrying the herpes simplex thymidine kinase (HSVtk) gene have been used in a number of human cancer gene therapy trials, however transduction has generally been limited to a small minority of tumor cells. To solve this problem, replication-competent adenoviral vectors carrying transgenes such as HSVtk have been developed. However, contradictory evidence exists regarding the efficacy of these new vectors. Accordingly, we constructed and tested a replication-competent E3-deleted adenoviral vector containing the HSVtk suicide gene driven by the endogenous E3 promoter (Ad.wt.tk). This virus showed high level production of the HSVtk transgene and was more efficacious than a non-replicating virus in vitro, after injection into flank tumors, and against established intraperitoneal tumors. However, addition of ganciclovir (GCV) therapy to cells or tumor-bearing animals treated with the replicating vector containing the HSVtk suicide gene did not result in increased cell killing. Our results indicate that addition of HSVtk to a replicating Ad virus will not likely be useful in augmenting antitumor effects.

Effects of Bowman-Birk inhibitor concentrate (BBIC) in patients with benign prostatic hyperplasia.

BACKGROUND: The Bowman-Birk inhibitor is a soybean-derived protease inhibitor that has anti-inflammatory and anticarcinogenic activities. METHODS: A Phase I trial of Bowman-Birk inhibitor concentrate (BBIC) in 19 male subjects with benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS) has been performed. RESULTS: The results of the trial indicated that there was no dose-limiting toxicity of BBIC. There was a statistically significant decrease in serum PSA levels in all BBIC-treated patients. Some BBIC-treated patients exhibited a relatively large reduction in serum PSA levels, ranging up to a 43% reduction. There was also a statistically significant decrease in serum triglyceride levels and a decrease in prostate volume in the treated patients. The scores recorded in response to a urinary symptom questionnaire indicated improved urinary activities in the BBIC-treated patients; however, the control subjects exhibited similar improvements in urinary activities during the course of the trial. CONCLUSIONS: The data obtained in this trial, particularly the data suggesting that BBIC treatment may lead to reduced serum PSA levels and reduced prostate volumes, suggest that a Phase II clinical trial of BBIC for the therapy of BPH is warranted.

Prospective evaluation of growth, nutritional status, and body composition in children with cystic fibrosis.

BACKGROUND: Several cross-sectional studies have shown improvement in the growth of children with cystic fibrosis (CF) because of increased awareness of and more comprehensive care of their special nutritional needs. However, longitudinal data on the nutritional status of these children are rare. OBJECTIVE: The objective was to compare changes in growth, body composition, and nutritional status between children with and without CF. DESIGN: This was a prospective 3-y cohort study of 25 children aged 5-10 y with CF, mild pulmonary disease, and pancreatic insufficiency and of 26 healthy control children. Three methods were used to assess body composition: measurements of skinfold thickness, total body water by deuterium oxide, and total-body electrical conductivity. Growth and body-composition changes over time were analyzed by a longitudinal mixed-effects model. RESULTS: Over the 3 y of the study, the statural growth of the boys with CF was slower than that of the control subjects (P = 0.004). The same divergence over time between the boys with and without CF was observed for fat-free mass assessed by skinfold-thickness measurements and total body water (P = 0.008 and 0.02, respectively) and for fat mass assessed by skinfold-thickness measurements and total-body electrical conductivity (P = 0.009 and 0.001, respectively). The differences in the pattern of changes in growth and body composition were less striking for girls. CONCLUSIONS: Despite comprehensive care, the growth of boys with CF was impaired on the basis of height, fat-free mass, and fat mass, when observed longitudinally. Caution should be used when interpreting cross-sectional measurements because they often do not detect suboptimal growth.

A prospective study of body composition changes in children with cystic fibrosis.

Recent cross-sectional studies of children with cystic fibrosis (CF) have shown an improvement in their growth with improved nutritional status, but there are only a few longitudinal studies in this population. A four-year prospective study was conducted in 25 children with CF and 26 controls, ages 5 to 10 years at baseline, to describe changes in body composition using three independent methods of assessment: skinfold thickness, total body water by deuterium dilution, and total body electrical conductivity (TOBEC). The statural growth of the boys with CF was slower than that of the control boys. Using different methods, the fat-free mass and fat-mass increases were shown to be slower in boys with CF than in controls. These differences were less significant in girls. Despite comprehensive care, the growth of boys with CF may still not be optimal, as observed longitudinally.

Treatments used in women with interstitial cystitis: the interstitial cystitis data base (ICDB) study experience. The Interstitial Cystitis Data Base Study Group.

OBJECTIVES: To evaluate the frequency and types of treatments reported at baseline in women who entered the Interstitial Cystitis Data Base (ICDB) cohort study. METHODS: From 1993 to 1997, 581 women were enrolled and followed in the ICDB. All treatments reported at study entry, including those prescribed for interstitial cystitis (IC) and concomitant medications, were reviewed. The number and types of treatments were evaluated with respect to baseline factors such as prior diagnosis of IC and symptom severity. RESULTS: One hundred five (18%) women were receiving no therapy at baseline. Single-mode therapy was reported by 195 (34%) women, and a combination of two treatments was reported by 119 (21%) women. Three or more treatments were reported in 162 (28%) women. A total of 183 different types of therapies were recorded. The five most commonly used therapies for IC symptoms were cystoscopy and hydrodistention, amitriptyline, phenazopyridine, special diet, and intravesical heparin. Because most patients entered the ICDB before the approval of oral pentosan polysulfate sodium (PPS), only 6% of women reported oral PPS use at baseline. There were statistically significant associations between the number and types of treatments and clinical center, a prior diagnosis of IC, and symptom severity. CONCLUSIONS: The diversity of IC therapies underscores the lack of understanding about the treatment of this syndrome. Further research in IC is essential to develop and to evaluate rational therapies and treatment algorithms. These algorithms should be "evidence based" and should be revised as the underlying etiology and pathophysiology of IC is delineated.

A prospective study of interstitial cystitis: results of longitudinal followup of the interstitial cystitis data base cohort. The Interstitial Cystitis Data Base Study Group.

PURPOSE: We present baseline characteristics and longitudinal profiles of symptoms in the Interstitial Cystitis Data Base study, a prospective cohort study of patients with interstitial cystitis. MATERIALS AND METHODS: A total of 637 eligible patients were entered into the study and followed for symptoms of pain, urgency and urinary frequency. Median followup was 31 months. RESULTS: More than 90% of patients were white women with a median age of 43 years. Using the overall pain-urgency-frequency score 7% of participants presented with mild, 44% with moderate and 49% with severe symptoms. Severe urgency in 41% of cases and severe 24-hour frequency in 41% were more common than severe pain in 29%. Of the patients 51% reported nighttime frequency of 2 or more voids. Median duration of interstitial cystitis symptoms was 8 years and 68% of participants were previously diagnosed with the condition. The 36% of patients who withdrew from study or were lost to followup were more likely to have had more severe symptoms at baseline. Patterns of change with time suggest initial symptom improvement due to regression to the mean, and an intervention effect associated with the increased followup and care of cohort participants. Although all symptoms fluctuated, there was no evidence of significant long-term change in overall disease severity. CONCLUSIONS: Our observations support the clinical observation that interstitial cystitis is a chronic disease and no current treatments have a significant impact on symptoms with time. These results provide a foundation for the design and performance of future clinical trials in interstitial cystitis using these end points in a similar patient population.

A phase I study of adenovirus-mediated transfer of the human cystic fibrosis transmembrane conductance regulator gene to a lung segment of individuals with cystic fibrosis.

A third-generation adenoviral vector containing recombinant human cystic fibrosis transmembrane conductance regulator (CFTR) gene was delivered by bronchoscope in escalating doses to the conducting airway of 11 volunteers with cystic fibrosis. Assessments of dose-limiting toxicity (DLT), efficiency of gene transfer, and cell-mediated and humoral immune responses to vector administration were performed. DLT, manifest by flulike symptoms and transient radiographic infiltrates, was seen at 2.1 x 10(11) total viral particles. A highly specific assay for gene transfer was developed using in situ hybridization with an oligoprobe against unique vector sequence. Detectable gene transfer was observed in harvested bronchial epithelial cells (<1%) 4 days after vector instillation, which diminished to undetectable levels by day 43. Adenovirus-specific cell-mediated T cells were induced in most subjects, although only mild increases in systemic humoral immune response were observed. These results demonstrate that gene transfer to epithelium of the lower respiratory tract can be achieved in humans with adenoviral vectors but that efficiency is low and of short duration in the native CF airway.

Discrepancies in pediatric bone mineral density reference data: potential for misdiagnosis of osteopenia.

OBJECTIVE: To evaluate published pediatric dual-energy x-ray absorptiometry bone mineral density (BMD) reference data by comparing the diagnostic classification of measured BMD in children at risk for osteopenia as healthy or osteopenic according to reference source. STUDY DESIGN: Spine BMD was measured in 95 children, ages 9 to 15 years, at risk for osteopenia because of childhood disease. The BMD results were converted to age-specific z scores for each of the 5 reference data sets, and the z -score distributions were compared. RESULTS: Between 11% and 30% of children were classified as osteopenic (z score < -2.0) depending on the reference data set. The 2 sex-specific reference data sets yielded similar diagnostic classification of boys and girls: 10% of boys and 11% to 16% of girls were osteopenic (P =.4). The 3 sex-nonspecific reference data sets classified 9% to 13% of girls and 24% to 44% of boys as osteopenic; the diagnosis of osteopenia was significantly greater in boys (P <.01). CONCLUSIONS: The use of different published reference data for the assessment of children at risk for osteopenia results in inconsistent diagnostic classification of BMD results. These inconsistencies can be partially attributed to sex-nonspecific reference data that result in misclassification of boys as osteopenic.