Methotrexate Polyglutamate Monitoring in Patients With Crohn's Disease.

Methotrexate is an efficacious immunosuppressant for induction and maintenance of remission in Crohn's disease. The goal of this pilot study was to determine whether total or individual methotrexate glutamate levels (MTXGlun ) in red blood cells correlate with disease activity and adverse events in Crohn's disease. A cross-sectional study was undertaken with 12 patients on a stable dose of 25 mg weekly methotrexate (oral or subcutaneous). Clinical disease activity was assessed by the Harvey-Bradshaw Index (HBI), and biologic disease activity was measured by inflammatory markers. Concentrations of individual MTXGlun levels were measured in red blood cells (RBCs) using high-performance liquid chromatography-mass spectrometry. No association was observed between RBC individual (MTXGlun ) or total methotrexate glutamate concentrations and clinical disease activity (HBI score) or inflammatory markers or adverse events. Although Crohn's disease patients in remission appeared to generally have higher RBC total longer-chain methotrexate polyglutamate (MTXGlu3+4+5 ) concentrations compared with those with active disease, a definitive association between RBC MTXGlu3+4+5 levels and clinical disease activity could not be established. Larger longitudinal studies in patients with diverse disease activity are needed to establish the value of MTXGlun levels as indicators of treatment efficacy and clinical outcome.

Predictors of Early Failure After Fecal Microbiota Transplantation for the Therapy of Clostridium Difficile Infection: A Multicenter Study.

OBJECTIVES: Fecal microbiota transplant (FMT) is a highly efficacious treatment for recurrent or refractory Clostridium difficile infection (CDI); however, 10-20% of patients fail to achieve cure after a single FMT. The aim of this study was to identify risk factors associated with FMT failure and to develop and validate a prediction model for FMT failure. METHODS: Patient characteristics, CDI history, FMT characteristics, and outcomes data for patients treated between 2011 and 2015 at three academic tertiary referral centers were prospectively collected. Early FMT failure was defined as non-response or recurrence of diarrhea associated with positive stool C. difficile toxin or PCR within 1 month of FMT. Late FMT failure was defined as recurrence of diarrhea associated with positive stool C. difficile toxin or PCR between 1 and 3 months of the FMT. Patient data from two centers were used to determine independent predictors of FMT failure and to build a prediction model. A risk index was constructed based on coefficients of final predictors. The patient cohort from the third center was used to validate the prediction model. RESULTS: Of 328 patients in the developmental cohort, 73.5% (N=241) were females with a mean age of 61.4±19.3 years; 19.2% (N=63) had inflammatory bowel disease (IBD), and 23.5% (N=77) were immunocompromised. The indication for FMT was recurrent CDI in 87.2% (N=286) and severe or severe-complicated in 12.8% (N=42). FMT was performed as an inpatient in 16.7% (N=54). The stool source was patient-directed donors in 40% (N=130) of cases. The early FMT failure rate was 18.6%, and the late failure rate was 2.7%. In the multivariable analysis, predictors of early FMT failure included severe or severe-complicated CDI (odds ratio (OR) 5.95, 95% confidence interval (CI): 2.26-15.62), inpatient status during FMT (OR 3.78, 95% CI: 1.55-9.24), and previous CDI-related hospitalization (OR 1.43, 95% CI: 1.18-1.75); with each additional hospitalization, the odds of failure increased by 43%. Risk scores ranged from 0 to 13, with 0 indicating low risk, 1-2 indicating moderate risk, and ≥3 indicating high risk. In the developmental cohort, early FMT failure rates were 5.6% for low risk, 12.7% for moderate risk, and 41% for high-risk patients. Of 134 patients in the validation cohort, 57% (N=77) were females with a mean age of 66±18.1 years; 9.7% (N=13) had IBD, and 17.9% (N=24) were immunocompromised. The early FMT failure rate at 1 month was 19.4%, with an additional 3% failing by 3 months. In the validation cohort, FMT failure rates were 2.1% for low risk, 16.1% for moderate risk, and 35.7% for high risk patients. The area under the receiver operating characteristic curve (AUROC) for FMT failure was 0.81 in the developmental cohort and 0.84 in the validation cohort. CONCLUSIONS: Severe and severe-complicated indication, inpatient status during FMT, and the number of previous CDI-related hospitalizations are strongly associated with early failure of a single FMT for CDI. The novel prediction model has good discriminative power at identifying individuals who are at high risk of failure after FMT therapy and may assist the treating physician in subsequent management plans.

Comparative Effectiveness on Cognitive Asthma Outcomes of the SHARP Academic Asthma Health Education and Counseling Program and a Non-Academic Program.

Asthma morbidity and mortality is higher among older school-age children and early adolescents than other age groups across the lifespan. NIH recommended expanding asthma education to schools and community settings to meet cognitive outcomes that have an impact on morbidity and mortality. Guided by the acceptance of asthma model, an evidence-guided, comprehensive school-based academic health education and counseling program, Staying Healthy-Asthma Responsible & Prepared™ (SHARP), was developed. The program complements existing school curricula by integrating biology, psychology, and sociology content with related spelling, math, and reading and writing assignments. Feasibility, benefits, and efficacy have been established. We compared the effectiveness of SHARP to a non-academic program, Open Airways for Schools, in improving asthma knowledge and reasoning about symptom management. A two-group, cluster-randomized, single-blinded design was used with a sample of 205 students in grades 4-5 with asthma and their caregivers. Schools were matched prior to randomization. The unit of analysis was the student. Certified elementary school teachers delivered the programs during instructional time. Data were collected from student/caregiver dyads at baseline and at 1, 12, and 24 months after the intervention. In multilevel modeling, students enrolled in the academic SHARP program demonstrated significant (p< .001) improvement in asthma knowledge and reasoning over students enrolled in the non-academic program. Knowledge advantages were retained at 24 months. Findings support delivery in schools of the SHARP academic health education program for students with asthma.

Effectiveness of a school-based academic asthma health education and counseling program on fostering acceptance of asthma in older school-age students with asthma.

PURPOSE: The purpose of this study was to evaluate the effectiveness of the academic asthma education and counseling Staying Healthy-Asthma Responsible and Prepared™ (SHARP) program on fostering psychosocial acceptance of asthma. DESIGN AND METHODS: This was a phase III, two-group, cluster-randomized, single-blinded, longitudinal study. Students from grades 4 and 5 (N = 205) with asthma and their caregivers completed surveys at pre-intervention and at 1-, 12-, and 24-months post-intervention. Analysis involved multilevel modeling. RESULTS: All students demonstrated significant improvement in aspects of acceptance; students in SHARP demonstrated significant improvement in openness to sharing and connectedness with teachers over students in the control condition. PRACTICE IMPLICATIONS: The SHARP program offers a well-tested, effective program for psychosocial acceptance of asthma, which is welcomed by schools.

Effectiveness of a school- and community-based academic asthma health education program on use of effective asthma self-care behaviors in older school-age students.

PURPOSE: The purpose was to evaluate the effectiveness of Staying Healthy-Asthma Responsible & Prepared, an academic asthma health education and counseling program, on fostering the use of effective asthma self-care behaviors. DESIGN AND METHODS: This was a phase III, two-group, cluster randomized, single-blinded, longitudinal design-guided study. Caregivers of 205 fourth- and fifth-grade students completed the asthma health behaviors survey at preintervention, and 1, 12, and 24 months postintervention. Analysis involved multilevel modeling. RESULTS: All students demonstrated improvement in episode management, risk reduction/prevention, and health promotion behaviors; Staying Healthy-Asthma Responsible & Prepared students demonstrated increased improvement in episode management and risk reduction/prevention behaviors. PRACTICE IMPLICATIONS: Working with schoolteachers, nurses can improve the use of effective asthma self-care behaviors.

Development and evaluation of an instrument to measure reasoning about managing asthma in older school-age children and adolescents.

BACKGROUND AND PURPOSE: This article describes development and evaluation of a 4-scenario instrument designed to measure reasoning abilities for managing asthma symptoms. METHODS: Existing literature informed creation of a reasoning template and the reasoning scenarios. Think-aloud interviews appraised scenario functionality. Experts assessed content validity. Data from 2 groups of students with asthma aged 9-15 years (N = 132 and 307) were used to evaluate psychometric properties. RESULTS: The scenarios were deemed functional, content was relevant, and readability was age/grade appropriate. Cronbach's alpha was 0.79. Exploratory and confirmatory factor analyses indicated a single component solution and revealed a good fit. Concurrent validity was established using correlations with asthma knowledge. CONCLUSION: The instrument could be used to assess reasoning about symptom management and to evaluate educational interventions.

Feasibility and benefits of a school-based academic and counseling program for older school-age students with asthma.

An asthma education program for older school-age students with asthma was developed in collaboration with school personnel, healthcare professionals, and community partners. Feasibility and benefits were evaluated using a single-group, prospective, quasi-experimental design. The convenience sample, consisting of 28 grade 6 and 7 students with asthma, had 50% males, a diverse racial background, and a wide range of incomes. Feasibility and benefits were demonstrated by comparing pre-intervention to 1- and 12-month post-intervention evaluation of students who completed more than 70% of the 10 sessions. Statistically significant improvements in cognitive, behavioral, psychosocial, and quality of life outcomes were seen from pre-intervention to 1-month post-intervention (all p < .03). Severity of asthma significantly improved from 1- to 12-month post-intervention (p= .04).