Validation of Math Model Using Porous Media for Determining Alveolar co2 in Ventilated Patients.

OBJECTIVES: To validate a mathematical model using porous media theory for alveolar CO2 determination in ventilated patients. DESIGN: Mathematical modeling study with prospective clinical validation to simulate CO2 exchange from bloodstream to airway entrance. SETTING: ICU. PATIENTS: Thirteen critically ill patients without chronic or acute lung disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Model outcomes compared with patient data showed correlations for end-tidal CO2 (EtCO2), area under the CO2 curve, and PaCO2 of 0.918, 0.954, and 0.995. Determination coefficients (R2) were 0.843, 0.910, and 0.990, indicating precision and predictive power. CONCLUSIONS: The mathematical model shows potential in pulmonary critical care. Although promising, practical application demands further validation, clinician training, and patient-specific adjustments. The path to clinical use will be iterative, involving validation and education.

Axial and peripheral spondyloarthritis: does psoriasis influence the clinical expression and disease burden? Data from REGISPONSER registry.

OBJECTIVE: To evaluate whether the presence of psoriasis influences the clinical expression, disease activity and disease burden in both axial and peripheral phenotypes of spondyloarthritis (SpA). METHODS: Patients from the Spanish REGISPONSER registry classified as having SpA according to the ESSG criteria were included. Patients were classified as psoriatic or non-psoriatic depending on the presence of cutaneous or nail psoriasis; thereafter, they were classified as having either axial [presence of radiographic sacroiliitis OR inflammatory back pain (IBP)] or peripheral phenotype (absence of radiographic sacroiliitis AND absence of IBP AND presence of peripheral involvement). Pair-wise univariate and multivariate analyses among the four groups (psoriatic/non-psoriatic axial phenotypes and psoriatic/non-psoriatic peripheral phenotypes) were performed with adjustment for treatment intake. RESULTS: A total of 2296 patients were included in the analysis. Among patients with axial phenotype, psoriasis was independently associated (P < 0.05) with HLA-B27+ [odds ratio (OR) 0.27], uveitis (OR 0.46), synovitis (ever) (OR 2.59), dactylitis (OR 2.78) and the use of conventional synthetic DMARDs (csDMARDs) (OR 1.47) in comparison with non-psoriatic patients. Among patients with peripheral phenotype and adjusting for csDMARD intake, psoriasis was independently associated with higher age at disease onset (OR 1.05), HLA-B27+ (OR 0.14) and heel enthesitis (OR 0.22). Higher scores for patient-reported outcomes and greater use of treatment at the time of the study visit were observed in psoriatic patients with either axial or peripheral phenotype. CONCLUSION: These findings suggest that, among all patients with SpA, psoriasis is associated with differences in clinical expression of SpA, a greater disease burden and increased use of drugs.

How to calculate the ASDAS based on C-reactive protein without individual questions from the BASDAI: the BASDAI-based ASDAS formula.

OBJECTIVES: To develop a new equation to calculate the Ankylosing Spondylitis Disease Activity Score based on CRP (ASDAS-CRP) using only the BASDAI total score and CRP. METHODS: Axial SpA (axSpA) patients from the Cordoba Spondyloarthritis Registry cohort were recruited as a derivation cohort, while a retrospective sample from the Spanish Rheumatology Society National Registry of Spondyloarthropathies and Ibero American Spondyloarhtritis Registry registers was used as a validation cohort. We built a new equation based only on the BASDAI and CRP, defining a new formula: the BASDAI-based ASDAS (BASDAS). Linear regression analysis was used to determine the coefficients of the equation in the derivation cohort and it was subsequently validated in the validation cohort. RESULTS: A total of 52 axSpA patients in the derivation cohort and 3359 patients in the validation cohort were included. In the derivation cohort, the mean BASDAS [2.24 (s.d. 0.90)] was very similar to the ASDAS-CRP [2.23 (s.d. 0.95)], with a very strong correlation (r = 0.96, P < 0.001). In the validation cohort, the mean BASDAS was 3.31 (s.d. 1.37) and the ASDAS-CRP was 3.19 (s.d. 1.27), which also had a very strong correlation (r = 0.95, P < 0.001). Intraclass correlation coefficients were excellent in both cohorts (0.963 and 0.947, respectively). CONCLUSION: The BASDAS performs similarly to the ASDAS-CRP and can be calculated with only the BASDAI total score and CRP, allowing evaluation of disease activity in retrospective studies where the individual items of the BASDAI are not available.

Hip and Shoulder Involvement and Their Management in Axial Spondyloarthritis: a Current Review.

PURPOSE OF REVIEW: Hip and shoulder disease can occur in patients with spondyloarthritis (SpA). While hip involvement has been widely assessed in axial SpA patients, studies in the overall SpA population as well as studies focused on shoulder involvement are scarce. Here, we review the most recent studies on the epidemiology, evaluation, and treatment of root joint involvement in SpA patients. RECENT FINDINGS: Radiological hip involvement can affect up to 25% of patients with SpA, reflecting more severe disease and associated with functional impairment. Shoulder involvement in SpA patients is characterized by cuff tendinitis and enthesitis, while primary glenohumeral joint involvement is rare. Anti-tumor necrosis factor (anti-TNF) treatment in SpA patients seems to have an effect on hip arthritis, showing a change in trend in the frequency of hip replacement in this population. The majority of studies evaluating hip involvement have focused on axial SpA patients, but further studies evaluating root joint involvement in the overall SpA population are needed. Anti-TNF therapy should be considered in patients with hip involvement, and root joint involvement should be assessed routinely in clinical practice.

13Check_RNA: a tool to evaluate 13C chemical shift assignments of RNA.

Motivation: Chemical shifts (CS) are an important source of structural information of macromolecules such as RNA. In addition to the scarce availability of CS for RNA, the observed values are prone to errors due to a wrong re-calibration or miss assignments. Different groups have dedicated their efforts to correct CS systematic errors on RNA. Despite this, there are not automated and freely available algorithms for evaluating the referencing of RNA 13 C CS before their deposition to the BMRB or re-reference already deposited CS with systematic errors. Results: Based on an existent method we have implemented an open source python module to correct 13 C CS (from here on 13Cexp) systematic errors of RNAs and then return the results in 3 formats including the nmrstar one. Availability and implementation: This software is available on GitHub at https://github.com/BIOS-IMASL/13Check_RNA under a MIT license. Supplementary information: Supplementary data are available at Bioinformatics online.

Michael addition of carbonyl compounds to nitroolefins under the catalysis of new pyrrolidine-based bifunctional organocatalysts.

Novel bifunctional pyrrolidine-based organocatalysts for the asymmetric Michael addition of carbonyl compounds to nitroolefins have been synthesised from homoallylamines, which are easily obtained from (R)-glyceraldehyde as a chiral precursor. Under optimal reaction conditions, these bifunctional organocatalysts showed a high catalytic efficiency (almost quantitative yield in most cases) and stereoselectivity in the Michael addition reactions of a variety of aldehydes (up to 98 : 2 dr and 97% ee) and ketones (up to 98 : 2 dr and 99% ee) to nitroolefins.

Serum P-glycoprotein level: a potential biomarker of DMARD failure in patients with rheumatoid arthritis.

OBJECTIVES: To evaluate the utility of elevated serum P-glycoprotein (P-gp) as a risk marker of therapeutic response failure in rheumatoid arthritis (RA) patients treated with disease-modifying antirheumatic drugs (DMARDs). METHODS: A cross-sectional study was conducted in 151 RA patients. Patients were classified into two groups according to the response achieved in terms of the disease activity score (DAS)28 after ≥ 6 months: (1) patients with a therapeutic response to DMARDs, with DAS28 < 3.2; and (2) patients without a response to DMARDs, with persistent DAS28 ≥ 3.2. We explored a wide group of clinical factors associated with therapeutic resistance. Serum P-gp levels were measured by ELISA. The risk of P-gp elevation as a marker of failure to achieve a therapeutic response to DMARDs was computed using multivariate logistic regression. RESULTS: Serum P-gp levels were significantly higher in RA patients (n = 151) than in the controls (n = 30) (158.70 ± 182.71 ng/mL vs. 14.12 ± 8.97 ng/mL, p < 0.001). The P-gp level was correlated with the DAS28 score (r = 0.39, p < 0.001). RA patients with DMARD failure had higher serum P-gp levels than patients with a therapeutic response (206 ± 21.47 ng/mL vs 120.60 ± 15.70 ng/mL; p = 0.001). High P-gp levels increased the risk of DMARD failure (OR 3.36, 95% CI 1.54-7.27, p = 0.001). After adjusting for confounding variables, elevated P-gp remained associated with DMARD failure (OR 2.64, 95% CI 1.29-5.40, p = 0.01). CONCLUSION: Elevated serum P-gp is associated with DMARD failure. The P-gp level can be considered a clinical tool for evaluating the risk of DMARD failure in patients; however, future prospective studies should be performed to evaluate the utility of this marker in predicting long-term responses.

Learning climate and feedback as predictors of dental students' self-determined motivation: The mediating role of basic psychological needs satisfaction.

AIM: The aim of this study was to test the mediating role of the satisfaction of dental students' basic psychological needs of autonomy, competence and relatedness on the association between learning climate, feedback and student motivation. The latter was based on the self-determination theory's concepts of differentiation of autonomous motivation, controlled motivation and amotivation. METHODS: A cross-sectional correlational study was conducted where 924 students completed self-reported questionnaires measuring motivation, perception of the learning climate, feedback and basic psychological needs satisfaction. Descriptive statistics, Cronbach's alpha scores and bivariate correlations were computed. Mediation of basic needs on each predictor-outcome association was tested based on a series of regression analyses. Finally, all variables were integrated into one structural equation model, controlling for the effects of age, gender and year of study. RESULTS: Cronbach's alpha scores were acceptable (.655 to .905). Correlation analyses showed positive and significant associations between both an autonomy-supportive learning climate and the quantity and quality of feedback received, and students' autonomous motivation, which decreased and became negative when correlated with controlled motivation and amotivation, respectively. Regression analyses revealed that these associations were indirect and mediated by how these predictors satisfied students' basic psychological needs. These results were corroborated by the structural equation analysis, in which data fit the model well and regression paths were in the expected direction. CONCLUSION: An autonomy-supportive learning climate and the quantity and quality of feedback were positive predictors of students' autonomous motivation and negative predictors of amotivation. However, this was an indirect association mediated by the satisfaction of students' basic psychological needs. Consequently, supporting students' needs of autonomy, competence and relatedness might lead to optimal types of motivation, which has an important influence on dental education.

Diagnostic potential of NETosis-derived products for disease activity, atherosclerosis and therapeutic effectiveness in Rheumatoid Arthritis patients.

OBJECTIVES: 1) To assess the association of NETosis and NETosis-derived products with the activity of the disease and the development of cardiovascular disease in RA; 2) To evaluate the involvement of NETosis on the effects of biologic therapies such as anti-TNF alpha (Infliximab) and anti-IL6R drugs (Tocilizumab). METHODS: One hundred and six RA patients and 40 healthy donors were evaluated for the occurrence of NETosis. Carotid-intimae media thickness was analyzed as early atherosclerosis marker. Inflammatory and oxidative stress mediators were quantified in plasma and neutrophils. Two additional cohorts of 75 RA patients, treated either with Infliximab (n = 55) or Tocilizumab (n = 20) for six months, were evaluated. RESULTS: NETosis was found increased in RA patients, beside myeloperoxidase and neutrophil elastase protein levels. Cell-free nucleosomes plasma levels were elevated, and strongly correlated with the activity of the disease and the positivity for autoantibodies, alongside inflammatory and oxidative profiles in plasma and neutrophils. Moreover, ROC analyses showed that cell-free nucleosomes levels could identify RA patients showing early atherosclerosis with high specificity. RA patients treated either with IFX or TCZ for six months exhibited decreased generation of NETs. Concomitantly, clinical parameters and serum markers of inflammation were found reduced. Mechanistic in vitro analyses showed that inhibition of NETs extrusion by either DNase, IFX or TCZ, further abridged the endothelial dysfunction and the activation of immune cells, thus influencing the global activity of the vascular system. CONCLUSIONS: NETosis-derived products may have diagnostic potential for disease activity and atherosclerosis, as well as for the assessment of therapeutic effectiveness in RA.

Prognostic Factors for Permanent Work Disability in Patients With Rheumatoid Arthritis Who Received Combination Therapy of Conventional Synthetic Disease-Modifying Antirheumatic Drugs: A Retrospective Cohort Study.

BACKGROUND: There is limited information about the factors related with the development of long-term permanent work disability (PWD) in rheumatoid arthritis (RA) treated with a combination of conventional synthetic disease-modifying antirheumatic drugs (cs-DMARDs). OBJECTIVE: The aim of this study was to evaluate incidence and factors associated with the development of PWD in RA treated with combination therapy using conventional synthetic cs-DMARDs. METHODS: We assessed in multivariate models the effect of clinical and demographic factors in the development of PWD in a long-term retrospective cohort of 180 workers with RA who were treated with a combination of cs-DMARDs. RESULTS: Incidence rates of PWD were 2.2% at 1 year, 7.7% at 5 years, 24.9% at 10 years, 34.9% at 15 years, and 45% at 20 years. In the adjusted Cox regression analysis, factors associated with PWD development were the first failure with combination of cs-DMARDs (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.05-5.46; P = 0.03), poor functioning at time of cohort onset (HR, 2.2; 95% CI, 1.05-4.70; P = 0.03), and requirement for joint replacement (HR, 3.3; 95% CI, 1.28-8.79; P = 0.01). CONCLUSIONS: Around 25% of workers with combination therapy with cs-DMARDs developed PWD in 10 years following the diagnosis of RA. Some factors increase the risk of disability. Permanent work disability generates a relevant society burden and increases health care costs. Therefore, indicators predicting failure of combination therapies with cs-DMARDs might provide clinicians of useful tools for modifying treatments avoiding the disease progression.

Association between bone turnover markers, clinical variables, spinal syndesmophytes and bone mineral density in Mexican patients with ankylosing spondylitis.

OBJECTIVES: To compare bone turnover marker (BTM) levels and bone mineral density (BMD) between patients with ankylosing spondylitis (AS) and healthy controls (HC) and to evaluate, in AS, the association between BTM levels and clinical variables, spinal syndesmophytes, and BMD using multivariate analysis. METHOD: Seventy-eight AS patients were compared with 58 HC matched by gender. Spinal syndesmophytes in AS and other characteristics were assessed. C-terminal telopeptide fragments of type I collagen (CTX), bone-specific alkaline phosphatase (BAP), osteocalcin (OC) serum levels, and BMD of the lumbar spine, femoral neck, and forearm were evaluated. RESULTS: AS males and females had lower BAP levels than their respective HC (p < 0.001 and p = 0.001). AS patients with bridging syndesmophytes had higher OC levels than AS patients either with non-bridging syndesmophytes (p = 0.001) or without spinal syndesmophytes (p < 0.001). OC and CTX levels correlated significantly with the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). In the multivariate linear regression adjusted by age, gender, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), BMD in the lumbar spine, and C-reactive protein (CRP), we observed an association between BAP levels and anti-tumour necrosis factor (anti-TNF) use (p = 0.05) whereas OC levels were associated with mSASSS (p < 0.001) and anti-TNF use (p = 0.05), and CTX levels were exclusively associated with mSASSS (p = 0.03). In the logistic regression analysis, only OC levels were associated with the presence of syndesmophytes in AS [odds ratio (OR) 2.42, 95% confidence interval (CI) 1.19-5.75]. CONCLUSIONS: We observed an increase in OC levels in AS patients with syndesmophytes. BTM levels were associated with the severity of spinal damage. Future longitudinal studies should evaluate whether these BTMs should be included as tools to determine the prognosis and progression of spinal damage.

Real-world cost-effectiveness of infliximab, etanercept and adalimumab in rheumatoid arthritis patients: results of the CREATE registry.

Biological drugs have proven efficacy and effectiveness in treatment of rheumatoid arthritis (RA), although none has been shown to be superior. Few studies have evaluated the cost-effectiveness of biological drugs in real-life clinical conditions. The objective of this study was to compare the cost-effectiveness of infliximab, etanercept and adalimumab in achieving clinical remission (DAS28 < 2.6) when used as initial biological therapy. Patients were diagnosed with RA who began treatment with infliximab, etanercept or adalimumab in the Reina Sofia Hospital (Cordoba, Spain) between January 1, 2007, and December 31, 2012. Effectiveness was measured as the percentage of patients who achieved clinical remission after 2 years. The cost analysis considered the use of direct health resources (perspective of the healthcare system). Cost-effectiveness was calculated by dividing the total mean cost of each treatment by the percentage of patients who achieved remission. One hundred and thirty patients were included: 55 with infliximab, 44 with adalimumab and 31 with etanercept. After 2 years, 45.2 % of patients with adalimumab achieved clinical remission, versus 29.1 % with infliximab (p = 0.133) and 22.7 % with etanercept (p = 0.040), with no differences between etanercept and infliximab (p = 0.475). The average total cost at 2 years was €29,858, €25,329 and €23,309 for adalimumab, infliximab and etanercept, respectively, while the mean cost (95 %CI) to achieve remission was €66,057 (48,038­84,076), €87,040 (78,496­95,584) and €102,683 (94,559­110,807), respectively. Adalimumab was more efficient than etanercept (p < 0.001) and infliximab (p = 0.026), with no differences between etanercept and infliximab (p = 0.086). Adalimumab was the most cost-effective treatment in achieving clinical remission in real-life clinical conditions in RA patients during the study period.

Cost-effectiveness of clinical remission by treat to target strategy in established rheumatoid arthritis: results of the CREATE registry.

To analyse the cost-effectiveness, in daily clinical practice, of the strategy of treating to the target of clinical remission (CR) in patients with established rheumatoid arthritis (RA), after 2 years of treatment with biological therapy. Adult patients with established RA were treated with biological therapy and followed up for 2 years by a multidisciplinary team responsible for their clinical management. Treatment effectiveness was evaluated by the DAS28 score. The direct costs incurred during this period were quantified from the perspective of the healthcare system. We calculated the cost-effectiveness of obtaining a DAS28 < 2.6, considered as CR. The study included 144 RA patients treated with biological therapies. After 2 years of treatment, 32.6% of patients achieved CR. The mean cost of achieving CR at 2 years was 79,681 ± 38,880 euros. The strategy of treatment to the target of CR is considered the most effective, but in actual clinical practice in patients with established RA, it has a high cost.

Inter-rater reliability of clinical mobility measures in ankylosing spondylitis.

BACKGROUND: Several measurements are often used in daily clinical practice in the assessment of Ankylosing Spondylitis (AS) patients. The Assessment in SpondyloArthiritis International Society (ASAS) recommend in its core set: chest expansion modified Schöber test, Occiput to wall distance, lateral lumbar flexion, cervical rotation and The Bath Ankylosing Spondylitis Metrology Index (BASMI). BASMI also includes five measurements, some of them recommended by ASAS. Three versions of BASMI have been published with different scales and intervals for each component of the index. Though studies about reliability of these measurements are needed. The aim of this study was to analyze inter-rater reliability of recommended spinal mobility measures in AS. METHODS: We examined reproducibility of spinal mobility measurements on 33 AS patients performed by two experienced rheumatologists in the same day. Descriptive statistics, Intraclass Correlation Coefficients (ICC), and Smallest Detectable Difference (SDD) using the Bland-Altman criteria were obtained for all the measurements. RESULTS: Chest expansion showed the lowest value of ICC (0.66) and occiput-wall the highest (0.97). SDD was 2.43 units for BASMI2 and 1.27 units for BASMI10. CONCLUSIONS: Reliability according to ICC was moderate to high in all measurements. BASMI10, instead BASMI2, must be used: measurements used to calculate are the same but there is better reliability. Inter-rater variation, expressed as SDD, must be taken in account: smaller improvements do not demonstrate the efficacy of treatment because they can be due to experimental error and not to the treatment itself.

Association between -174G/C and -572G/C interleukin 6 gene polymorphisms and severe radiographic damage to the hands of Mexican patients with rheumatoid arthritis: a preliminary report.

Several interleukin 6 gene (IL6) polymorphisms are implicated in susceptibility to rheumatoid arthritis (RA). It has not yet been established with certainty if these polymorphisms are associated with the severe radiographic damage observed in some RA patients, particularly those with the development of joint bone ankylosis (JBA). The objective of the present study was to evaluate the association between severe radiographic damage in hands and the -174G/C and -572G/C IL6 polymorphisms in Mexican Mestizo people with RA. Mestizo adults with RA and long disease duration (>5 years) were classified into two groups according to the radiographic damage in their hands: a) severe radiographic damage (JBA and/or joint bone subluxations) and b) mild or moderate radiographic damage. We compared the differences in genotype and allele frequencies of -174G/C and -572G/C IL6 polymorphisms (genotyped using polymerase chain reaction-restriction fragment length polymorphism) between these two groups. Our findings indicated that the -174G/C polymorphism of IL6 is associated with severe joint radiographic damage [maximum likelihood odds ratios (MLE_OR): 8.03; 95%CI 1.22-187.06; P = 0.03], whereas the -572G/C polymorphism of IL6 exhibited no such association (MLE_OR: 1.5; 95%CI 0.52-4.5; P = 0.44). Higher anti-cyclic citrullinated peptide antibody levels were associated with more severe joint radiographic damage (P = 0.04). We conclude that there is a relevant association between the -174G/C IL6 polymorphism and severe radiographic damage. Future studies in other populations are required to confirm our findings.

Dimension of chronic hepatitis C virus in HIV-infected patients in the interferon-free era: an overview from south Spain.

The implementation of hepatitis C (HCV) direct-acting antiviral drugs is prioritized in several populations in which its application provides the most immediate and impactful benefit. In this scenario, a precise knowledge of the situation of human immunodeficiency virus (HIV)/HCV chronic co-infection is required to adequately address this disease. This cross-sectional study was performed in 21 hospitals in Andalusia (Spain). The study population consisted of HIV-infected patients with an active HCV chronic infection who were not receiving HCV treatment at the time of inclusion. A total of 13,506 HIV-infected patients were included in the study. Of them, 2561 (18.9 %) presented chronic HCV infection. The majority of the patients included were on highly active antiretroviral therapy (HAART; 96.2 %), showed plasma levels with an undetectable HIV viral load (92.5 %), and had a good immunological status (median CD4+ cell count of 486 cells/mL). The HCV genotype distribution was as follows: 58.1 % were genotype 1, 1.1 % were genotype 2, 16.1 % were genotype 3, and 22.1 % were genotype 4 (2.6 % were missing data). In total, 24.8 % of the patients showed liver fibrosis stage F0-F1, 27.9 % showed stage F2, 16.7 % showed stage F3, and 21 % showed stage F4 (9.6 % were missing data). With regards to previous HCV treatment experiences, 68.05 % of the patients were naïve and 31.95 % had failed to respond to a previous treatment. The burden of HCV/HIV co-infected patients in our population was reported as one in five HIV-infected patients requiring HCV treatment. The implementation of extra resources to face this important health challenge is mandatory.

Efficacy of and risk of bleeding during pegylated interferon plus ribavirin treatment in HIV/HCV-coinfected patients with pretreatment thrombocytopenia.

The aim of this study was to assess the efficacy of and the risk of major bleeding during pegylated interferon (peg-IFN)/ribavirin (RBV) treatment among human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients according to the pretreatment platelet count. Two hundred and seventy-four HCV/HIV-coinfected, previously naïve individuals with compensated cirrhosis enrolled in one Spanish prospective cohort who received peg-IFN/RBV were included in this study. The frequency of severe bleeding and sustained virological response (SVR) rate were compared between patients with a pretreatment platelet count ≤70,000/mm(3) and >70,000/mm(3), respectively. Sixty-one (22 %) patients had a baseline platelet count ≤70,000/mm(3). The median (Q1-Q3) pretreatment platelet count was 58,000 (49,000-65,000) cells/mm(3) in the platelet ≤70,000 group and 129,000 (102,500-166,000) cells/mm(3) in the platelet >70,000 group (p < 0.0001). Seventeen (28 %) subjects of the platelet ≤70,000 group and 71 (33 %) patients of the platelet >70,000 group achieved SVR (p = 0.4). Only 2 (3.2 %) patients in the platelet ≤70,000 group developed a severe hemorrhagic event, specifically esophageal variceal bleeding. The efficacy of therapy with peg-IFN/RBV in HIV/HCV-coinfected patients with low pretreatment platelet counts is comparable to that found in the overall subset of subjects with compensated cirrhosis. The frequency of severe hemorrhagic events related with this therapy is low in this population.

Development of urine standard reference materials for metabolites of organic chemicals including polycyclic aromatic hydrocarbons, phthalates, phenols, parabens, and volatile organic compounds.

Two new Standard Reference Materials (SRMs), SRM 3672 Organic Contaminants in Smokers' Urine (Frozen) and SRM 3673 Organic Contaminants in Non-Smokers' Urine (Frozen), have been developed in support of studies for assessment of human exposure to select organic environmental contaminants. Collaborations among three organizations resulted in certified values for 11 hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) and reference values for 11 phthalate metabolites, 8 environmental phenols and parabens, and 24 volatile organic compound (VOC) metabolites. Reference values are also available for creatinine and the free forms of caffeine, theobromine, ibuprofen, nicotine, cotinine, and 3-hydroxycotinine. These are the first urine Certified Reference Materials characterized for metabolites of organic environmental contaminants. Noteworthy, the mass fractions of the environmental organic contaminants in the two SRMs are within the ranges reported in population survey studies such as the National Health and Nutrition Examination Survey (NHANES) and the Canadian Health Measures Survey (CHMS). These SRMs will be useful as quality control samples for ensuring compatibility of results among population survey studies and will fill a void to assess the accuracy of analytical methods used in studies monitoring human exposure to these organic environmental contaminants.

A single-center experience of cytomegalovirus infections in Asian pediatric patients undergoing allogeneic hematopoietic stem cell transplant for leukemia in Singapore.

INTRODUCTION: Cytomegalovirus (CMV) infection remains a significant cause of morbidity and mortality in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) despite improved surveillance and the current preemptive approach. Few data on its prevalence in the Asian pediatric population exist. METHODS: We retrospectively reviewed the prevalence of CMV infections in 33 patients with 37 transplants who received HSCT for leukemia from 1998 to 2008, and who were managed preemptively for infections. RESULTS: In the 37 transplants, 16 patients (43%) had CMV DNAemia. Of the patients who were CMV seropositive before transplant and received stem cells from seropositive donors (R+/D+), 69% had DNAemia; of those who received stem cells from seronegative donors (R+/D-), 36% had CMV DNAemia. Of the patients who were CMV naïve before transplant and received stem cells from seropositive donors (R-/D+), 25% had CMV DNAemia. In CMV-seronegative donor-recipient transplants (R-/D-), 20% of patients had CMV DNAemia. The median time to the first episode of CMV DNAemia was 21 (range: 10-107) days after the transplants, and the median duration of CMV DNAemia was 22 (range: 2-315) days. CMV DNAemia recurred in 44% (7 of 16) of these patients. Only 1 patient developed CMV disease (retinitis). No deaths were related to CMV infections. CONCLUSIONS: CMV infection manifesting as DNAemia is a common complication in pediatric patients undergoing allogeneic HSCT for leukemia. Pre-transplant serostatus predicts reactivation risks; invasive CMV disease is rare using the preemptive approach in our patient population.