Natural History of Pediatric Patients With Crohn's Disease Treated With Mesalamine Therapy.

Background: 5-aminosalicylates (5-ASA) are used to treat mild to moderate ulcerative colitis. Despite their lack of efficacy in Crohn disease (CD), they are still used in real-world practice. Additionally, when patients have progressive disease, they may escalate to biologic therapy, at which time 5-ASA may or may not be discontinued. Objectives: The aim of this study is to assess the clinical outcomes of patients started on 5-ASA for the treatment of pediatric CD. The secondary aims were to evaluate the outcomes of those who continue 5-ASA to those who discontinue 5-ASA upon biologic escalation. Methods: We performed a single-center retrospective chart review of pediatric CD patients from 2010 to 2019 who were initially treated with 5-ASA. Demographics, medication and laboratory data, and clinical disease activity were collected. Results: Sixty-one patients were included in the study; the majority had inflammatory CD with ileocolonic involvement. Twenty-four patients were on a concomitant immunomodulator. The majority of patients (85.2%) required escalation to biologics. Thirty-two patients (61.5%) who escalated to biologic therapy continued on 5-ASA. Eighty percent of patients achieved clinical remission at 1 year, and there was no difference between those who continued 5-ASA at time of biologic initiation compared to those who did not continue the medication. Patients who discontinued 5-ASA had an average annual cost savings of $6741. Conclusion: 5-ASA is not a durable monotherapy for the treatment of pediatric CD. Patients who require escalation from 5-ASA to biologic therapy do not benefit from concomitant 5-ASA therapy. Further prospective studies are needed to confirm these findings.

Differences in Clinical Presentation of Eosinophilic Esophagitis in Pediatric Patients With Ulcerative Colitis and Crohn Disease.

SIGNIFICANCE: Eosinophilic esophagitis (EoE) is an inflammatory condition characterized by T helper-2 (T H 2) cytokines. Ulcerative colitis (UC) and Crohn disease (CD) are inflammatory conditions with different clinical presentations and immune profiles. UC is associated with T H 2 cytokines and CD with T H 1 cytokines. We investigated potential differences in the association of EoE with UC and CD because of these different immune profiles. METHODS: We utilized ICD-9 and ICD-10 codes to find patients with inflammatory bowel disease (IBD) and EoE. We defined EoE as any esophageal biopsy with >15 eosinophils. We collected demographic, clinical, laboratory, endoscopic, and histological data. RESULTS: Thirty patients had both EoE and IBD. 14.9% of UC patients had EoE and 5.7% of CD patients had EoE. 64.7% of UC patients presented with UC and EoE at the same time, whereas 76.9% of CD patients presented with EoE at follow up. Ten of 13 CD patients were on anti-tumor necrosis factor (TNF) at EoE diagnosis. No UC patients were on anti-TNF at EoE diagnosis. Eighty-three percent of CD patients had mild disease or were in remission, whereas 50% of UC patients had moderate to severe disease at the time of EoE diagnosis. CONCLUSION: A higher percentage of UC than CD patients had EoE. EoE was more likely to be present at the initial diagnosis of UC than CD. EoE was more likely after diagnosis and treatment of CD with anti-TNF, when CD activity was mild or in remission. The difference in presentation suggests that anti-TNF or it's impact on inflammation may differentially impact the association of EoE with CD and UC.

Association of Fecal Calprotectin With Endoscopic and Histologic Activity in Pediatric Inflammatory Bowel Disease.

Fecal calprotectin (FC) is a noninvasive marker of intestinal inflammation used for screening and ongoing monitoring of inflammatory bowel disease (IBD); it is unclear the association of specific FC values with disease activity. The aim of our study was to examine the association of FC values with endoscopic and histologic severity. Methods: We performed a retrospective chart review of patients who had FC done between 30 days and 1 day before colonoscopy at our institution. IBD patients were graded using the simple endoscopic score for Crohn's disease or Mayo endoscopic score for ulcerative colitis. Histologic slides were graded using the Geboes method. Results: Three-hundred thirty-one patients were included in the study and 107 had IBD. For endoscopy, median FC was lowest for all IBD patients with no disease (181 µg/g) and highest in severe disease (921 µg/g), with significant difference between no disease and moderate and severe disease (P = 0.019, 0.003), and between mild and severe disease (P = 0.012). For histology, median FC was lowest with no disease (328 µg/g) and highest in severe disease (895 µg/g), with significant difference between no disease and moderate and severe disease (P = 0.021, 0.018). The control population had a significantly lower median FC than the IBD population in endoscopic remission (35.5 versus 181 µg/g; P = 0.018). Conclusions: There was a linear increase in FC values associated with increasing disease severity in the undifferentiated IBD cohort. Values for IBD patients in endoscopic remission were significantly different from our control population. FC may be a useful noninvasive marker to assess disease severity.

Evaluating a Standardized Transition of Care Process for Pediatric Inflammatory Bowel Disease Patients.

To reduce lapses in care for pediatric inflammatory bowel disease (IBD) patients approaching adulthood, a health maintenance transition visit (HMV) was developed to supplement standard medical care (SMV). Our aim was to assess the effect of the HMV on transition readiness. A retrospective chart review was conducted at a single center with demographics and clinical data from HMV and SMV visits. Effectiveness of the HMV was assessed by the patient health questionanaire-9 (PHQ-9) and transition readiness assessment questionnaire (TRAQ) scores. A total of 140 patients, 80% Caucasian and 59% male completed an HMV. The mean age was 18 ± 2 years old, and 93% of patients reported inactive or mild disease. Patients who completed at least 1 prior HMV scored significantly higher on the TRAQ when transferring to adult care compared to patients transferred at their first HMV visit (92 vs. 83, p < 0.05). Of patients with no prior depression diagnosis, 36% had a positive screen for depression. A significant relationship was identified between disease status and PHQ-9 (p < 0.05). This study demonstrated a structured HMV increased transition readiness and quantified the significant under-diagnosis of depression in this population, emphasizing the importance of screening. These results indicate depression may affect patients' transition preparedness.

Journey towards universal viral load monitoring in Maputo, Mozambique: many gaps, but encouraging signs.

Introduction: Viral load (VL) monitoring for people on antiretroviral therapy (ART) is extremely challenging in resource-limited settings. We assessed the VL testing scale-up in six Médecins Sans Frontières supported health centres in Maputo, Mozambique, during 2014-15. Methods: In a retrospective cohort study, routine programme data were used to describe VL testing uptake and results, and multi-variate logistical regression to estimate predictors of VL testing uptake and suppression. Results: Uptake of a first VL test was 40% (17 236/43 579). Uptake of a follow-up VL test for patients with a high first VL result was 35% (1095/3100). Factors associated with a higher uptake included: age below 15 years, longer time on ART and attending tailored service delivery platforms. Virological suppression was higher in pregnant/breastfeeding women and in community ART Group members. Patients with a high first VL result (18%; 3100/17 236) were mostly younger, had been on ART longer or had tuberculosis. Out of 1095 attending for a follow-up VL test, 678 (62%) had virological failure. Of those, less than one-third had started second line ART. Conclusion: This was the first study describing the uptake and results of VL testing scale-up in Mozambique. Identified gaps show patient and programmatic challenges. Where service delivery was customized to patient needs, VL monitoring was more successful.

Swim drink study: a randomised controlled trial of during-exercise rehydration and swimming performance.

OBJECTIVE: To determine whether during-exercise rehydration improves swimming performance and whether sports drink or water have differential effects on performance. DESIGN: Randomised controlled multiple crossover trial. SETTING: A UK competitive swimming club. SUBJECTS: 19 club-level competitive swimmers, median age (range) 13 (11-17) years. INTERVENTIONS: Subjects were scheduled to drink ad libitum commercial isotonic sports drink (3.9 g sugars and 0.13 g salt per 100 mL) or water (three sessions each) or no drink (six sessions) in the course of twelve 75 min training sessions, each of which was followed by a 30 min test set of ten 100 m maximum-effort freestyle sprints each starting at 3 min intervals. MAIN OUTCOME MEASURE: Times for the middle 50 m of each sprint measured using electronic timing equipment in a Federation Internationale de Natation (FINA)-compliant six-lane 25 m competition swimming pool. RANDOMISATION: Software-generated individual random session order in sealed envelopes. Analysis subset of eight sessions randomly selected by software after data collection completed. MASKING: Participants blind to drink allocation until session start. RESULTS: In the analysis data set of 1118 swims, there was no significant difference between swim times for drinking and not drinking nor between drinking water or a sports drink. Mean (SEM) 50 m time for no-drink swims was 38.077 (0.128) s and 38.105 (0.131) s for drink swims, p=0.701. Mean 50 m times were 38.031 (0.184) s for drinking sports drink and 38.182 (0.186) s for drinking water, p=0.073. Times after not drinking were 0.027 s faster than after drinking (95% CI 0.186 s faster to 0.113 s slower). Times after drinking sports drink were 0.151 s faster than after water (95% CI 0.309 s faster to 0.002 s slower). Mean (SEM) dehydration from exercise was 0.42 (0.11)%. CONCLUSIONS: Drinking water or sports drink over 105 min of sustained effort swimming training does not improve swimming performance. TRIAL REGISTRATION: ISRCTN: 49860006.

Comparison of two methods - regression predictive model and intake shift model - for adjusting self-reported dietary recall of total energy intake of populations.

Daily dietary intake data derived from self-reported dietary recall surveys are widely considered inaccurate. In this study, methods were developed for adjusting these dietary recalls to more plausible values. In a simulation model of two National Health and Nutrition Examination Surveys (NHANES), NHANES I and NHANES 2007-2008, a predicted one-third of raw data fell outside a range of physiologically plausible bounds for dietary intake (designated a 33% failure rate baseline). To explore the nature and magnitude of this bias, primary data obtained from an observational study were used to derive models that predicted more plausible dietary intake. Two models were then applied for correcting dietary recall bias in the NHANES datasets: (a) a linear regression to model percent under-reporting as a function of subject characteristics and (b) a shift of dietary intake reports to align with experimental data on energy expenditure. After adjustment, the failure rates improved to <2% with the regression model and 4-9% with the intake shift model - both substantial improvements over the raw data. Both methods gave more reliable estimates of plausible dietary intake based on dietary recall and have the potential for more far-reaching application in correction of self-reported exposures.

Community-supported models of care for people on HIV treatment in sub-Saharan Africa.

OBJECTIVES: Further scale-up of antiretroviral therapy (ART) to those in need while supporting the growing patient cohort on ART requires continuous adaptation of healthcare delivery models. We describe several approaches to manage stable patients on ART developed by Médecins Sans Frontières together with Ministries of Health in four countries in sub-Saharan Africa. METHODS: Using routine programme data, four approaches to simplify ART delivery for stable patients on ART were assessed from a patient and health system perspective: appointment spacing for clinical and drug refill visits in Malawi, peer educator-led ART refill groups in South Africa, community ART distribution points in DRC and patient-led community ART groups in Mozambique. RESULTS: All four approaches lightened the burden for both patients (reduced travel and lost income) and health system (reduced clinic attendance). Retention in care is high: 94% at 36 months in Malawi, 89% at 12 months in DRC, 97% at 40 months in South Africa and 92% at 48 months in Mozambique. Where evaluable, service provider costs are reported to be lower. CONCLUSION: Separating ART delivery from clinical assessments was found to benefit patients and programmes in a range of settings. The success of community ART models depends on sufficient and reliable support and resources, including a flexible and reliable drug supply, access to quality clinical management, a reliable monitoring system and a supported lay workers cadre. Such models require ongoing evaluation and further adaptation to be able to reach out to more patients, including specific groups who may be challenged to meet the demands of frequent clinic visits and the integrated delivery of other essential chronic disease interventions.

Decreasing intestinal parasites in recent Northern California refugees.

Beginning in 2005, the Centers for Disease Control and Prevention (CDC) expanded the overseas presumptive treatment of intestinal parasites with albendazole to include refugees from the Middle East. We surveyed the prevalence of helminths and protozoa in recent Middle Eastern refugees (2008-2010) in comparison with refugees from other geographical regions and from a previous survey (2001-2004) in Santa Clara County, California. Based on stool microscopy, helminth infections decreased, particularly in Middle Eastern refugees (0.1% versus 2.3% 2001-2004, P = 0.01). Among all refugees, Giardia intestinalis was the most common protozoan found. Protozoa infections also decreased somewhat in Middle Eastern refugees (7.2%, 2008-2010 versus 12.9%, 2001-2004, P = 0.08). Serology for Strongyloides stercoralis and Schistosoma spp. identified more infected individuals than stool exams. Helminth infections are increasingly rare in refugees to Northern California. Routine screening stool microscopy may be unnecessary in all refugees.

Clinical application and limitations of interferon-gamma release assays for the diagnosis of latent tuberculosis infection.

Interferon-release assays (IGRAs) represent advances in tuberculosis immunology and evolutionary biology. IGRAs were designed to replace tuberculin skin test (TST) for the diagnosis of latent tuberculosis infection because of their logistical advantages and enhanced specificity over TST. Although IGRAs and TST have been useful in epidemiologic studies, they lack the sensitivity and reproducibility normally expected from diagnostic tests in clinical practice. In this review, we present an overview of the current recommendations and knowledge in the field and discuss practical approaches in areas of uncertainty related to discordant IGRA results.

Th1/Th2 cytometric bead array can discriminate cytokine secretion from endogenously activated cells in pulmonary disease, recent and remote infection in tuberculosis.

Differential T cell trafficking through the blood compartment towards infected foci may be occurring in different stages of tuberculosis disease and infection. The aim of the present study was to identify cytokine signatures in the blood compartment in tuberculosis patients with pulmonary disease (PTB=19), recently exposed household contacts (HC=27) and nonexposed community controls (EC=37). Diluted (1:10) whole blood was cultured for 2 days and cytokine secretion was assessed using Cytometric Bead Array (Th1/Th2 kit II; BD Biosciences) which included IL-2, TNF-α, IFN-γ (Type1/T1), IL-4, IL-6 and IL-10 (Type2/T2). All T1/T2 cytokines were elevated in PTB (AUROC>0.9) while HC showed selective elevation of IL-6 (AUROC>0.7) compared to EC. Principal component analysis (PCA) extracted two groupings with Eigen values >1; IL-6 separated into the second component for PTB, HC and EC. After rotation, IFN-γ was correlated with the first component for PTB and EC and the second component for HC indicating an absence of T1/T2 dichotomy. Therefore endogenous cytokine signatures may indicate differential T cell trafficking in different stages of tuberculosis infection and disease.

Vitamin d deficiency and tuberculosis progression.

To assess the association between vitamin D deficiency and tuberculosis disease progression, we studied vitamin D levels in a cohort of tuberculosis patients and their contacts (N = 129) in Pakistan. Most (79%) persons showed deficiency. Low vitamin D levels were associated with a 5-fold increased risk for progression to tuberculosis.

Infection with Helicobacter pylori is associated with protection against tuberculosis.

BACKGROUND: Helicobacter pylori, a lifelong and typically asymptomatic infection of the stomach, profoundly alters gastric immune responses, and may benefit the host in protection against other pathogens. We explored the hypothesis that H. pylori contributes to the control of infection with Mycobacterium tuberculosis. METHODOLOGY/PRINCIPAL FINDINGS: We first examined M. tuberculosis-specific IFN-gamma and H. pylori antibody responses in 339 healthy Northern Californians undergoing routine tuberculin skin testing. Of 97 subjects (29%) meeting criteria for latent tuberculosis (TB) infection (LTBI), 45 (46%) were H. pylori seropositive. Subjects with LTBI who were H. pylori-seropositive had 1.5-fold higher TB antigen-induced IFN-gamma responses (p = 0.04, ANOVA), and a more Th-1 like cytokine profile in peripheral blood mononuclear cells, compared to those who were H. pylori seronegative. To explore an association between H. pylori infection and clinical outcome of TB exposure, we evaluated H. pylori seroprevalence in baseline samples from two high risk TB case-contact cohorts, and from cynomolgus macaques experimentally challenged with M. tuberculosis. Compared to 513 household contacts who did not progress to active disease during a median 24 months follow-up, 120 prevalent TB cases were significantly less likely to be H. pylori infected (AOR: 0.55, 95% CI 0.0.36-0.83, p = 0.005), though seroprevalence was not significantly different from non-progressors in 37 incident TB cases (AOR: 1.35 [95% CI 0.63-2.9] p = 0.44). Cynomolgus macaques with natural H. pylori infection were significantly less likely to progress to TB 6 to 8 months after M. tuberculosis challenge (RR: 0.31 [95% CI 0.12-0.80], p = 0.04). CONCLUSIONS/SIGNIFICANCE: H. pylori infection may induce bystander effects that modify the risk of active TB in humans and non-human primates. That immunity to TB may be enhanced by exposure to other microbial agents may have important implications for vaccine development and disease control.

Real-time PCR testing for mecA reduces vancomycin usage and length of hospitalization for patients infected with methicillin-sensitive staphylococci.

Nucleic acid amplification tests (NAATs) have revolutionized infectious disease diagnosis, allowing for the rapid and sensitive identification of pathogens in clinical specimens. Real-time PCR testing for the mecA gene (mecA PCR), which confers methicillin resistance in staphylococci, has the added potential to reduce antibiotic usage, improve clinical outcomes, lower health care costs, and avoid emergence of drug resistance. A retrospective study was performed to identify patients infected with methicillin-sensitive staphylococcal isolates who were receiving vancomycin treatment when susceptibility results became available. Vancomycin treatment and length of hospitalization were compared in these patients for a 6-month period before and after implementation of mecA PCR. Among 65 and 94 patients identified before and after mecA PCR, respectively, vancomycin usage (measured in days on therapy) declined from a median of 3 days (range, 1 to 44 days) in the pre-PCR period to 1 day (range, 0 to 18 days) in the post-PCR period (P < 0.0001). In total, 38.5% (25/65) of patients were switched to beta-lactam therapy in the pre-PCR period, compared to 61.7% (58/94) in the post-PCR period (P = 0.004). Patient hospitalization days also declined from a median of 8 days (range, 1 to 47 days) in the pre-PCR period to 5 days (range, 0 to 42 days) in the post-PCR period (P = 0.03). Real-time PCR testing for mecA is an effective tool for reducing vancomycin usage and length of stay of hospitalized patients infected with methicillin-sensitive staphylococci. In the face of ever-rising health care expenditures in the United States, these findings have important implications for improving outcomes and decreasing costs.

Reproducibility of QuantiFERON-TB gold in-tube assay.

Studies are needed to characterize the reproducibility of QuantiFERON-TB Gold (QFT-G) for targeted U.S. screening populations. Members of northern California households were tested with the QFT-G in-tube assay (QFT-G-IT) at two home visits 3 months apart. Reproducibility and agreement with the tuberculin skin test (TST) were assessed. Monte Carlo simulation was used to evaluate the role of test-related error. Of 63 individuals (49 adults and 14 children) completing QFT-G-IT at both time points, 79% were foreign-born (98% from Latin America) and 68% reported Mycobacterium bovis BCG vaccination. At the baseline visit, 23 (37%) were TST positive and 15 (24%) were QFT-G-IT positive (kappa = 0.48 [+/- 0.11]). At 3 months, 3/48 (6.3%; 95% confidence interval [95CI], 2 to 17) of those initially QFT-G-IT negative converted, and 5/15 (33%; 95CI, 15 to 58) of those initially QFT-G-IT positive reverted. Among the 8 individuals with inconsistent QFT-G-IT results, the maximum gamma interferon response at either visit was 0.68 IU/ml versus means of 4.99 (+/- 3.74) and 6.95 (+/- 5.6) for 10 persistent positives at the first and second visits, respectively. Expected false-reversion and -conversion rates were 32% (90CI, 25 to 39%) and 6.95% (90CI, 4.6 to 9.8%) when the sensitivity and specificity were assumed to average 70% and 98%, respectively. Transient responses to QFT-G-IT are common, and low positive results need to be interpreted with caution. Further studies are needed to characterize the predictive value of the test for U.S. foreign-born and other targeted screening populations.

Gastroenteritis and transmission of Helicobacter pylori infection in households.

The mode of transmission of Helicobacter pylori infection is poorly characterized. In northern California, 2,752 household members were tested for H. pylori infection in serum or stool at a baseline visit and 3 months later. Among 1,752 person considered uninfected at baseline, 30 new infections (7 definite, 7 probable, and 16 possible) occurred, for an annual incidence of 7% overall and 21% in children <2 years of age. Exposure to an infected household member with gastroenteritis was associated with a 4.8-fold (95% confidence interval [CI] 1.4-17.1) increased risk for definite or probable new infection, with vomiting a greater risk factor (adjusted odds ratio [AOR] 6.3, CI 1.6-24.5) than diarrhea only (AOR 3.0, p = 0.65). Of probable or definite new infections, 75% were attributable to exposure to an infected person with gastroenteritis. Exposure to an H. pylori-infected person with gastroenteritis, particularly vomiting, markedly increased risk for new infection.

Risk of intestinal helminth and protozoan infection in a refugee population.

With continuing emigration from endemic countries, screening for parasitic infections remains a priority in U.S. communities serving refugee and immigrant populations. We report the prevalence of helminths and protozoa as well as demographic risk factors associated with these infections among 533 refugees seen at the Santa Clara County, California, Refugee Clinic between October 2001 and January 2004. Stool parasites were identified from 14% of refugees, including 9% found to have one or more protozoa and 6% found to have at least one helminth. Most common protozoan infections were Giardia lamblia (6%) and Dientamoeba fragilis (3%), and for helminths, hookworm (2%). Protozoa were more frequent in refugees < 18 years of age (OR: 2.2 [1.2-4.2]), whereas helminths were more common in refugees from South Central Asia (OR: 8.0 [2.3-27.7]) and Africa (OR: 5.9 [1.6-21.6]) when compared with refugees from Eastern Europe and the Middle East. Among helminths, Ascaris lumbricoides and hookworm were concentrated among South Central Asians (6 of 7 and 10 of 11 cases, respectively), whereas Strongyloides stercoralis was predominantly found in Africans (5 of 7 cases). Although predeparture empirical treatment programs in Saharan Africa may have helped to reduce prevalence among arriving refugees from this region, parasitic infection is still common among refugees to the United States with helminth infections found in more specific populations. As refugees represent only a fraction of recent immigrants from endemic countries, current studies in nonrefugee groups are also needed.

Helicobacter pylori infection in different generations of Hispanics in the San Francisco Bay Area.

To quantify the contributions of household and environmental factors to Helicobacter pylori infection, the authors examined H. pylori infection among several generations of Hispanics in the San Francisco Bay Area. Between 2000 and 2004, household members were tested for H. pylori and interviewed about demographic factors and household pedigree. An immigrant was defined as someone born in Latin America with at least one Latin America-born parent; a first-generation US-born Hispanic was defined as someone born in the United States with at least one Latin America-born parent; and a second-generation US-born Hispanic was defined as someone born in the United States with at least one US-born parent. Prevalences of H. pylori in immigrants and first- and second-generation US-born Hispanics were 31.4% (102/325), 9.1% (98/1,076), and 3.1% (2/64), respectively. Compared with second-generation US-born Hispanics, the age-adjusted odds ratios for H. pylori were 9.70 (95% confidence interval (CI): 1.57, 60.00) for immigrants and 4.32 (95% CI: 0.69, 26.96) for first-generation US-born Hispanics (p(trend) < 0.001). These odds ratios decreased to 6.19 (95% CI: 1.13, 33.77) and 3.24 (95% CI: 0.59, 17.82), respectively, after adjustment for parental infection (odds ratio (OR) = 2.94, 95% CI: 1.59, 4.38), low education (OR = 1.76, 95% CI: 1.20, 2.68), and crowding (OR = 1.23, 95% CI: 0.84, 1.79). Both the household and birth-country environments probably contributed to declining H. pylori prevalence among successive generations of Hispanics.