Background: Although exhaled breath condensate (EBC) pH has been identified as an "emerging" biomarker of interest for asthma clinical trials, the clinical determinants of EBC pH remain poorly understood. Other studies have associated acid reflux-induced respiratory symptoms, for example, cough, with transient acidification of EBC. Objective: We sought to determine the clinical and physiologic correlates of EBC acidification in a highly characterized sample of children with poorly controlled asthma. We hypothesized that (1) children with asymptomatic gastroesophageal reflux determined by 24-hour esophageal pH monitoring would have a lower EBC pH than children without gastroesophageal reflux, (2) treatment with lansoprazole would alter EBC pH in those children, and (3) EBC acidification would be associated with increased asthma symptoms, poorer asthma control and quality of life, and increased formation of breath nitrogen oxides (NOx). Methods: A total of 110 children, age range 6 to 17 years, with poor asthma control and esophageal pH data enrolled in the Study of Acid Reflux in Children with Asthma (. NCT00442013) were included. Children submitted EBC samples for pH and NOx measurement at randomization and at study weeks 8, 16, and 24. Results: Serial EBC pH measurements failed to distinguish asymptomatic gastroesophageal reflux and was not associated with breath NOx formation. EBC pH also did not discriminate asthma characteristics such as medication and health care utilization, pulmonary function, and asthma control and quality of life both at baseline and across the study period. Conclusion: Despite the relative ease of EBC collection, EBC pH as a biomarker does not provide useful information of children with asthma who were enrolled in asthma clinical trials.
by
Chaim Putterman;
Alan Wu;
Anat Reiner-Benaim;
D. Scott Batty;
Ignacio Sanz;
Jim Oates;
Keren Jakobi;
Michelle Petri;
Pennina Safer;
Robert Gerwien;
Rachel Sorek;
Yakov Blumenstein;
Irun R. Cohen
We describe here the development, verification and validation of the SLE-key® rule-out test for a definitive rule-out of a diagnosis of systemic lupus erythematosus (SLE). The test uses the proprietary iCHIP® micro-array technology platform (Fattal et al., 2010) to identify discriminating patterns of circulating autoantibodies among SLE patients compared with self-declared healthy individuals. Given the challenges associated with the diagnosis of SLE and the healthcare costs of delayed diagnosis and misdiagnosis, a definitive rule-out test can provide significant clinical benefits to patients and potentially major cost savings to healthcare systems.
by
Ionut Bebu;
Janet Tate;
David Rimland;
Octavio Mesner;
Grace E. Macalino;
Anuradha Ganesan;
Jason F. Okulicz;
Mary Bavaro;
Amy C. Weintrob;
Amy C. Justice;
Brian K. Agan
Background: The Veterans Aging Cohort Study (VACS) index is a weighted combination of age and 8 clinical variables. It has been well correlated with all-cause mortality among HIV-infected patients. The US Military HIV Natural History Study (NHS) cohort provides a different validation population profile, being younger and healthier. A significant portion of the US HIV population is similarly composed; so, evaluation of the VACS index in this population is of great interest.
Methods: NHS subjects have medical history and laboratory data collected at 6-month visits. We performed an external validation of the VACS index in the NHS evaluating correlation, discrimination, and calibration for all-cause mortality after highly active antiretroviral therapy initiation (HI). We then tested whether combining longitudinal VACS index values at different time points improves prediction of mortality.
Results: The VACS index at 1 year after HI was well correlated with all-cause mortality (Harrell c statistic 0.78), provided good discrimination (log-rank P < 0.05), and was marginally well calibrated using Brier score. Accounting for VACS index at HI and 6 months after HI significantly improved a standard model, including only the VACS index at 1 year after HI (net reclassification improvement = 25.2%, 95% CI: 10.9% to 48.9%).
Conclusions: The VACS index was well correlated and provided good discrimination with respect to all-cause mortality among highly active antiretroviral therapy initiating subjects in the NHS. Moderate overprediction of mortality in this young, healthy population suggests minor recalibration that could improve fit among similar patients. Considering VACS index at HI and 6 months improved outcome prediction and allowed earlier risk assessment.
by
Julie A. Womack;
Terrence E. Murphy;
Harini Bathulapalli;
Kathleen M. Akgun;
Cynthia Gibert;
Ken M. Kunisaki;
David Rimland;
Maria Rodriguez-Barradas;
H. Klar Yaggi;
Amy C. Justice;
Nancy S. Redeker
Background: HIV infection is clinically managed with antiretroviral therapy (ART), but only with sustained adherence. Cost-efficient interventions to improve and sustain ART adherence remain a pressing priority for populations challenged by nonadherence. The aim of this study was to test the independent and interactive effects of (1) brief phone-delivered self-regulation counseling and (2) daily phone-delivered text message medication reminders on HIV adherence and HIV viral suppression. Method: A randomized 2 (5 sessions of phone-delivered adherence support counseling vs. contact-matched control) × 2 (daily ART text reminders vs. no reminders) trial with primary end points of monthly phone-based unannounced pill count-determined ART adherence and HIV viral suppression monitored over 12 months. Results: Self-regulation adherence counseling demonstrated significant improvements in achieving 90% ART adherence relative to the control group over the first 6 months of follow-up. Effects remained significant in sensitivity analyses conducted at 85% and 95% adherence. Counseling also demonstrated modest but significant effects on HIV suppression. There were no main effects or interactions for daily text message reminders, with some evidence for adverse effects on adherence self-efficacy. Conclusions: Brief adherence support counseling delivered by phone demonstrates clinically meaningful improvements in ART adherence and HIV suppression, although these benefits were not evidenced in all patients or in the long-term. Advancing adherence interventions along with an effective means for sustaining gains in adherence remain priorities if ART is to achieve its potential clinical and public health benefits.
by
Geovani Faddoul;
Girish N. Nadkarni;
Nancy D. Bridges;
Jens Goebel;
Donald E. Hricik;
Richard Formica;
Madhav C. Menon;
Yvonne Morrison;
Barbara Murphy;
Kenneth Newell;
Peter Nickerson;
Emilio D. Poggio;
David Rush;
Peter S. Heeger
Background An early posttransplant biomarker/surrogate marker for kidney allograft loss has the potential to guide targeted interventions. Previously published findings, including results from the Clinical Trials in Organ Transplantation (CTOT)-01 study, showed that elevated urinary chemokine CXCL9 levels and elevated frequencies of donor-reactive interferon gamma (IFNγ)-producing T cells by enzyme-linked immunosorbent spot (ELISPOT) assay associated with acute cellular rejection within the first year and with lower 1-year posttransplant estimated glomerular filtration rate (eGFR). How well these biomarkers correlate with late outcomes, including graft loss, is unclear. Methods In CTOT-17, we obtained 5-year outcomes in the CTOT-01 cohort and correlated them with (a) biomarker results and (b) changes in eGFR (Chronic Kidney Disease Epidemiology Collaboration formula) over the initial 2 years posttransplant using univariable analysis and multivariable logistic regression. Results Graft loss occurred in 14 (7.6%) of 184 subjects 2 to 5 years posttransplant. Neither IFNγ ELISPOTs nor urinary CXCL9 were informative. In contrast, a 40% or greater decline in eGFR from 6 months to 2 years posttransplant independently correlated with 13-fold odds of 5-year graft loss (adjusted odds ratio, 13.1; 95% confidence interval, 3.0-56.6), a result that was validated in the independent Genomics of Chronic Allograft Rejection cohort (n = 165; adjusted odds ratio, 11.2). Conclusions We conclude that although pretransplant and early posttransplant ELISPOT and chemokine measurements associate with outcomes within 2 years posttransplant, changes in eGFR between 3 or 6 months and 24 months are better surrogates for 5-year outcomes, including graft loss.
Objective:To assess the performance of an adapted American Diabetes Association (ADA) risk score and the concise Finnish Diabetes Risk Score (FINRISC) for predicting type 2 diabetes development in women with and at risk of HIV infection.Design:Longitudinal analysis of the Women's Interagency HIV Study.Methods:The women's Interagency HIV Study is an ongoing prospective cohort study of women with and at risk for HIV infection. Women without prevalent diabetes and 3-year data on fasting blood glucose, hemoglobin A1c, self-reported diabetes medication use, and self-reported diabetes were included. ADA and FINRISC scores were computed at baseline and their ability to predict diabetes development within 3 years was assessed [sensitivity, specificity and area under the receiver operating characteristics (AUROC) curve].Results:A total of 1111 HIV-positive (median age 41, 60% African American) and 454 HIV-negative women (median age 38, 63% African-American) were included. ADA sensitivity did not differ between HIV-positive (77%) and HIV-negative women (81%), while specificity was better in HIV-negative women (42 vs. 49%, P = 0.006). Overall ADA discrimination was suboptimal in both HIV-positive [AUROC = 0.64 (95% CI: 0.58, 0.70)] and HIV-negative women [AUROC = 0.67 (95% CI: 0.57, 0.77)]. FINRISC sensitivity and specificity did not differ between HIV-positive (72 and 49%, respectively) and HIV-negative women (86 and 52%, respectively). Overall FINRISC discrimination was suboptimal in HIV-positive [AUROC = 0.68 (95% CI: 0.62, 0.75)] and HIV-negative women [AUROC = 0.78 (95% CI: 0.66, 0.90)].Conclusion:Model performance was suboptimal in women with and at risk of HIV, while greater misclassification was generally observed among HIV-positive women. HIV-specific risk factors known to contribute to diabetes risk should be explored in these models.
by
Anne Fitzpatrick;
Scott E. Gillespie;
David T. Mauger;
Brenda R. Phillips;
Eugene R. Bleecker;
Elliot Israel;
Deborah A. Meyers;
Wendy C. Moore;
Ronald L. Sorkness;
Sally E. Wenzel;
Leonard B. Bacharier;
Mario Castro;
Loren C. Denlinger;
Serpil C. Erzurum;
John V. Fahy;
Benjamin M. Gaston;
Nizar N. Jarjour;
Allyson Larkin;
Bruce D. Levy;
Ngoc P. Ly;
Victor E. Ortega;
Stephen P. Peters;
Wanda Phipatanakul;
Sima Ramratnam;
W. Gerald Teague
Background:
Despite advances in asthma care, disparities persist. Black patients are disproportionally affected by asthma and also have poorer outcomes compared with white patients.
Objective:
We sought to determine associations between black and white patients and asthma-related health care use, accounting for complex relationships.
Methods:
This study was completed as part of the National Heart, Lung, and Blood Institute's Severe Asthma Research Program, a prospective observational cohort. Between November 2012 and February 2015, it enrolled 579 participants 6 years and older with 1 year of observation time and complete data. Inverse probability of treatment weighting was used to balance racial groups with respect to community and family socioeconomic variables and environmental exposure variables. The primary outcome was emergency department (ED) use for asthma. Secondary outcomes included inhaled corticosteroid use, outpatient physician's office visits for asthma, and asthma–related hospitalization.
Results:
Black patients had greater odds of ED use over 1 year (odds ratio, 2.19; 95% CI, 1.43-3.35) but also differed in the majority (>50%) of baseline variables measured. After statistical balancing of the racial groups, the difference between black and white patients with respect to ED use no longer reached the level of significance. Instead, in secondary analyses black patients were less likely to see an outpatient physician for asthma management (adjusted odds ratio, 0.57; 95% CI, 0.38-0.85).
Conclusions:
The disparity in ED use was eliminated after consideration of multiple variables. Social and environmental policies and interventions tailored to black populations with a high burden of asthma are critical to reduction (or elimination) of these disparities.
Background: Success in multidrug-resistant tuberculosis (MDR-TB) and HIV treatment requires high medication adherence despite high pill burdens, frequent adverse events, and long treatment duration, which may jeopardize adherence. We prospectively compared MDR-TB/HIV-coinfected persons to those with MDR-TB alone to determine the impact of concurrent treatment on adherence and outcomes. Methods: We assessed medication adherence monthly using 3-day recall, 30-day recall, and visual analog scale and examined adherence to monthly study visits (months 0-12). We determined the proportion of participants fully adherent (no reported missed doses) to MDR-TB vs. HIV treatment by each measure. We assessed the association of medication and clinic visit adherence with MDR-TB treatment success (cure or completion, 18-24 months) and HIV virologic suppression. Results: Among 200 patients with MDR-TB, 63% were women, median age was 33 years, 144 (72%) were HIV-infected, and 81% were receiving antiretroviral therapy (ART) at baseline. Adherence to medications (81%-98% fully adherent across all measures) and clinic visits (80% missed ≤1 visit) was high, irrespective of HIV status. Adherence to ART was significantly higher than to MDR-TB treatment by all self-reported measures (3-day recall: 92% vs. 84%, respectively; P = 0.003). In multivariable analysis, the adjusted risk ratio of unsuccessful MDR-TB treatment increased with every missed visit: 1.50, 2.25, and 3.37 for unsuccessful treatment, for 1, 2, and ≥3 missed visits. Conclusions: Adherence to ART was higher than to MDR-TB treatment among persons with MDR-TB/HIV coinfection. Missed clinic visits may be a simple measure for identifying patients at risk of unsuccessful MDR-TB treatment outcome.
by
Vincent Marconi;
Cristina Cardemil;
T Pindyck;
AJ Hall;
JE Tate;
AK Kambhampati;
ME Wikswo;
DC Payne;
S Grytdal;
JA Boom;
JA Englund;
EJ Klein;
N Halasa;
R Selvarangan;
MA Staat;
GA Weinberg;
DO Beenhouwer;
ST Brown;
M Holodniy;
C Lucero-Obusan;
MC Rodriguez-Barradas;
U Parashar
International Classification of Diseases diagnostic codes are used to estimate acute gastroenteritis (AGE) disease burden. We validated AGE-related codes in pediatric and adult populations using 2 multiregional active surveillance platforms. The sensitivity of AGE codes was similar (54% and 58%) in both populations and increased with addition of vomiting-specific codes.