Publications

BACKGROUND

Placing inpatients with presumed active pulmonary tuberculosis in respiratory isolation pending results of serial sputum acid-fast bacilli (AFB) smear microscopy is standard practice in high-income countries. However, this diagnostic strategy is slow and yields few tuberculosis diagnoses. We sought to determine if replacing microscopy with the GeneXpert MTB/RIF (Xpert) nucleic acid amplification assay could reduce testing time and usage of isolation rooms.

METHODS

We prospectively followed inpatients at San Francisco General Hospital undergoing tuberculosis evaluation. We performed smear microscopy and Xpert testing on concentrated sputum, and calculated diagnostic accuracy for both strategies in reference to serial sputum mycobacterial culture. We measured turnaround time for microscopy and estimated hypothetical turnaround times for Xpert on concentrated and unconcentrated sputum. We compared median and total isolation times for microscopy to those estimated for the 2 Xpert strategies.

RESULTS

Among 139 patients with 142 admissions, median age was 54 years (interquartile range [IQR], 43-60 years); 32 (23%) patients were female, and 42 (30%) were HIV seropositive. Serial sputum smear microscopy and a single concentrated sputum Xpert had identical sensitivity (89%; 95% confidence interval [CI], 52%-100%) and similar specificity (99% [95% CI, 96%-100%] vs 100% [95% CI, 97%-100%]). A single concentrated sputum Xpert could have saved a median of 35 hours (IQR, 24-36 hours) in unnecessary isolation compared with microscopy, and a single unconcentrated sputum Xpert, 45 hours (IQR, 35-46 hours).

CONCLUSIONS

Replacing serial sputum smear microscopy with a single sputum Xpert could eliminate most unnecessary isolation for inpatients with presumed tuberculosis, greatly benefiting patients and hospitals.

BACKGROUND

Allergic rhinitis is a common disease whose genetic basis is incompletely explained. We report an integrated genomic analysis of allergic rhinitis.

METHODS

We performed genome wide association studies (GWAS) of allergic rhinitis in 5633 ethnically diverse North American subjects. Next, we profiled gene expression in disease-relevant tissue (peripheral blood CD4+ lymphocytes) collected from subjects who had been genotyped. We then integrated the GWAS and gene expression data using expression single nucleotide (eSNP), coexpression network, and pathway approaches to identify the biologic relevance of our GWAS.

RESULTS

GWAS revealed ethnicity-specific findings, with 4 genome-wide significant loci among Latinos and 1 genome-wide significant locus in the GWAS meta-analysis across ethnic groups. To identify biologic context for these results, we constructed a coexpression network to define modules of genes with similar patterns of CD4+ gene expression (coexpression modules) that could serve as constructs of broader gene expression. 6 of the 22 GWAS loci with P-value ≤ 1x10-6 tagged one particular coexpression module (4.0-fold enrichment, P-value 0.0029), and this module also had the greatest enrichment (3.4-fold enrichment, P-value 2.6 × 10-24) for allergic rhinitis-associated eSNPs (genetic variants associated with both gene expression and allergic rhinitis). The integrated GWAS, coexpression network, and eSNP results therefore supported this coexpression module as an allergic rhinitis module. Pathway analysis revealed that the module was enriched for mitochondrial pathways (8.6-fold enrichment, P-value 4.5 × 10-72).

CONCLUSIONS

Our results highlight mitochondrial pathways as a target for further investigation of allergic rhinitis mechanism and treatment. Our integrated approach can be applied to provide biologic context for GWAS of other diseases.

To determine Latino parents' beliefs on the health effects of beverages on infants and toddlers, their sources of information on beverages and perceived barriers to following guidelines for healthy beverage consumption by children. We conducted 29 interviews with parents of Latino children ages 6-36 months. Parents were recruited in three community health centers in Northern California. The interviews were recorded, transcribed and analyzed using standard qualitative methods. The following dominant themes emerged. Parents believed that water and milk were healthy beverages for children and that sugar-sweetened beverages (SSBs) were unhealthy. Views on 100% fruit juice were mixed. Parents distinguished between homemade beverages such as "agua fresca" which they considered healthy, despite containing added sugar, and beverages from stores which were viewed as unhealthy. Participants' main source of information on beverages was the federal nutrition program for Women, Infants, and Children (WIC). Parents were confused, however, as to why WIC provides juice yet counseled parents to avoid giving their children juice. Parents preferred to receive information on beverages from experts. Differing practices among family members regarding which beverages they provide to children was the most important barrier to following beverage guidelines. Our study suggests that Latino parents are receptive to counseling on beverages from expert sources. Such counseling should address both store-bought and homemade beverages. The WIC program is a key source of information on beverages for Latino parents; thus counseling offered by WIC should be evidence-based and avoid mixed messages.

Early linkage to care and engagement in care are critical for initiation of medical interventions. However, over 50 % of newly diagnosed persons do not receive HIV-related care within 6 months of diagnosis. We evaluated a linkage to care and engagement in care initiative for HIV-positive adolescents in 15 U.S.-based clinics. Structural and client-level factors (e.g. demographic and behavioral characteristics, clinic staff and location) were evaluated as predictors of successful linkage and engagement. Within 32 months, 1,172/1,679 (69.8 %) of adolescents were linked to care of which 1,043/1,172 (89 %) were engaged in care. Only 62.1 % (1,043/1,679) of adolescents were linked and engaged in care. Linkage to care failure was attributed to adolescent, provider, and clinic-specific factors. Many adolescents provided incomplete data during the linkage process or failed to attend appointments, both associated with failure to linkage to care. Additional improvements in HIV care will require creative approaches to coordinated data sharing, as well as continued outreach services to support newly diagnosed adolescents.