Publications

OBJECTIVES

Patients with inflammatory bowel disease (IBD) often experience barriers to subspecialty access. We applied telemedicine, using a new computerized system called Collaborative Imaging, to resolve these barriers. We studied patients' experience and satisfaction, and clinic throughput.

METHODS

We performed a prospective randomized controlled pilot study at a Veterans Affairs hospital, assigning patients into two groups: telemedicine encounter, with the IBD specialist remotely located, and standard encounter. We assessed patient experience and measured differences in satisfaction as well as clinic metrics such as appointment duration, wait time, and throughput.

RESULTS

We enrolled 34 patients with Crohn's disease and ulcerative colitis who underwent 57 encounters in 9 months. Patients were mostly Caucasian men, with a mean age of 61 years. The two groups similarly rated as excellent their clinic experience and the major clinical satisfaction indices of attention to patient concerns, bedside manner, and perceived skill level of the doctor. The total clinic duration, wait time, and median number of patients per clinic were also similar. The fellow and subspecialist highly rated the technical and informational quality of the telemedicine sessions.

CONCLUSIONS

IBD outpatient service may be delivered via a novel telemedicine system. In this pilot study, we observed a high level of patient satisfaction similar to that achieved with a direct clinical encounter.

BACKGROUND

Professional organizations have called for individualized training approaches, as well as for opportunities for resident scholarship, to ensure that internal medicine residents have sufficient knowledge and experience to make informed career choices.

CONTEXT AND PURPOSE

To address these training issues within the University of California, San Francisco, internal medicine program, we created the Areas of Distinction (AoD) program to supplement regular clinical duties with specialized curricula designed to engage residents in clinical research, global health, health equities, medical education, molecular medicine, or physician leadership. We describe our AoD program and present this initiative's evaluation data. METHODS AND PROGRAM EVALUATION: We evaluated features of our AoD program, including program enrollment, resident satisfaction, recruitment surveys, quantity of scholarly products, and the results of our resident's certifying examination scores. Finally, we described the costs of implementing and maintaining the AoDs.

RESULTS

AoD enrollment increased from 81% to 98% during the past 5 years. Both quantitative and qualitative data demonstrated a positive effect on recruitment and improved resident satisfaction with the program, and the number and breadth of scholarly presentations have increased without an adverse effect on our board certification pass rate.

CONCLUSIONS

The AoD system led to favorable outcomes in the domains of resident recruitment, satisfaction, scholarship, and board performance. Our intervention showed that residents can successfully obtain clinical training while engaging in specialized education beyond the bounds of core medicine training. Nurturing these interests 5 empower residents to better shape their careers by providing earlier insight into internist roles that transcend classic internal medicine training.

Until recently, relationships between evidence of colonization or infection by specific microbial species and the development, persistence or exacerbation of pulmonary disease have informed our opinions of airway microbiology. However, recent applications of culture-independent tools for microbiome profiling have revealed a more diverse microbiota than previously recognized in the airways of patients with chronic pulmonary disease. New evidence indicates that the composition of airway microbiota differs in states of health and disease and with severity of symptoms and that the microbiota, as a collective entity, may contribute to pathophysiologic processes associated with chronic airway disease. Here, we review the evolution of airway microbiology studies of chronic pulmonary disease, focusing on asthma, chronic obstructive pulmonary disease and cystic fibrosis. Building on evidence derived from traditional microbiological approaches and more recent culture-independent microbiome studies, we discuss the implications of recent findings on potential microbial determinants of respiratory health or disease.

BACKGROUND

Gene variants associated with disease could reveal novel mechanisms. We searched for single nucleotide polymorphisms (SNPs) associated with noncardioembolic stroke (nonCES).

METHODS

We tested 24,926 SNPs in or near genes for association with nonCES in the Vienna Study (551 cases, 815 controls) and then evaluated the associated SNPs in the UCSF-CC Study (570 cases, 1,604 controls) first in pooled DNA samples and then in individual DNA samples. We then asked whether the risk alleles of the SNPs associated with increased risk in both studies were also associated with increased risk of nonCES in the German Study (728 cases, 1,041 controls).

RESULTS

Six of the 46 SNPs that were associated with nonCES in both the Vienna and the UCSF-CC Studies were also associated with nonCES in the German Study: rs362277 in HTT (OR 1.39, 90% CI 1.12-1.71), rs2924914 near CSMD1 (OR 1.22, 90% CI 1.04-1.43), rs1264352 near DDR1 (OR 1.20, 90% CI 1.02-1.41), rs544115 in NEU3 (OR 1.63, 90% CI 1.02-2.62), rs12481805 in UMODL1 (OR 1.31, 90% CI 1.01-1.81), and rs2857595 near NCR3 (OR 1.15, 90% CI 1.00-1.32). Accounting for multiple testing of 46 SNPs, these 6 SNPs had a false discovery rate of 0.69.

CONCLUSIONS

Some of the 6 SNPs may be associated with nonCES but most may be false positives. These 6 SNPs merit investigation in additional nonCES study populations.

OBJECTIVE

Genetic studies may help explain abnormalities of fat distribution in HIV-infected patients treated with antiretroviral therapy (ARV).

METHODS

Subcutaneous adipose tissue (SAT) volume measured by MRI in the leg, the lower trunk, the upper trunk, and the arm was examined in 192 HIV-infected White men, ARV-treated from the Fat Redistribution and Metabolic Change in HIV infection study. Single-nucleotide polymorphisms were assayed using the Illumina Human CNV370-quad beadchip. Multivariate and univariate genome-wide association analyses of the four SAT depots were implemented in PLINK software adjusted for age and ARV duration. Functional annotation analysis using Ingenuity Systems Pathway Analysis tool was carried out for markers with P lower than 10(-3) near known genes identified by multivariate analysis.

RESULTS

Loci (rs10504906, rs13267998, rs921231) in or near the anion exchanger solute carrier family 26, member 7 isoform a (SLC26A7) were strongly associated with the upper trunk and the arm SAT (9.8×10(-7) ≤P<7.8×10(-6)). Loci (rs193139, rs7523050, rs1761621) in and near a gene-rich region including G-protein-signaling modulator 2 (GPSM2) and syntaxin-binding protein 3 (STXBP3) were significantly associated with the lower body SAT depots (9.9×10(-7) ≤P<9.5×10(-6)). GPSM2 is associated with cell division and cancer whereas STXBP3 is associated with glucose metabolism in adipoctyes. Ingenuity Systems Pathway Analysis identified atherosclerosis, mitochondrial function, and T-cell-mediated apoptosis as processes related to SAT volume in HIV-infected individuals (P<5×10(-3)).

CONCLUSION

Our results are limited by the small sample size and replication is needed; however, this genomic scan uncovered new genes associated with metabolism and inflammatory pathways that may affect SAT volume in ARV-treated HIV-infected patients.

The extracellular Ca(2+) -sensing receptor (CaR), a G protein-coupled receptor responsible for maintenance of calcium homeostasis, is implicated in regulation of skeletal metabolism. To discern the role of the osteoblast CaR in regulation of bone development and remodeling, we generated mice in which the CaR is excised in a broad population of osteoblasts expressing the 3.6-kb a(1) (I) collagen promoter. Conditional knockouts had abnormal skeletal histology at birth and developed progressively reduced mineralization secondary to retarded osteoblast differentiation, evident by significantly reduced numbers of osteoblasts and decreased expression of collagen I, osteocalcin, and sclerostin mRNAs. Elevated expression of ankylosis protein, ectonucleotide pyrophosphatase/phosphodiesterase 1, and osteopontin mRNAs in the conditional knockout indicate altered regulation of genes important in mineralization. Knockout of the osteoblast CaR also resulted in increased expression of the receptor activator of NF-κB ligand (RANKL), the major stimulator of osteoclast differentiation and function, consistent with elevated osteoclast numbers in vivo. Osteoblasts from the conditional knockouts exhibited delayed differentiation, reduced mineralizing capacity, altered expression of regulators of mineralization, and increased ability to promote osteoclastogenesis in coculture experiments. We conclude that CaR signaling in a broad population of osteoblasts is essential for bone development and remodeling and plays an important role in the regulation of differentiation and expression of regulators of bone resorption and mineralization.

It is generally accepted that informed patients have better health outcomes. Wright Nunes et al. report low levels of perceived chronic kidney disease (CKD) knowledge among patients treated in a nephrology clinic and describe a low-to-moderate association between perceived and objective CKD knowledge. Association of these two types of knowledge with health behaviors and clinical outcomes should be further explored to inform the development and evaluation of CKD educational interventions as well as communication between nephrologists and patients.

With earlier institution of antiretroviral therapy, kidney diseases other than HIV-associated nephropathy (HIVAN) predominate in HIV-infected persons. Outcomes for these diseases are typically worse among those infected with HIV, but the reasons for this are not clear. Here, we examined the role of APOL1 risk variants in predicting renal histopathology and progression to ESRD in 98 HIV-infected African Americans with non-HIVAN kidney disease on biopsy. We used survival analysis to determine time to ESRD associated with APOL1 genotype. Among the 29 patients with two APOL1 risk alleles, the majority (76%) had FSGS and 10% had hypertensive nephrosclerosis. In contrast, among the 54 patients with one APOL1 risk allele, 47% had immune-complex GN as the predominant lesion and only 23% had FSGS. Among the 25 patients with no APOL1 risk allele, 40% had immune-complex GN and 12% had FSGS. In 310 person-years of observation, 29 patients progressed to ESRD. In adjusted analyses, individuals with two APOL1 risk alleles had a nearly three-fold higher risk for ESRD compared with those with one or zero risk alleles (P=0.03). In summary, these data demonstrate an association between APOL1 variants and renal outcomes in non-HIVAN kidney disease, suggesting a possible use for APOL1 genotyping to help guide the care of HIV-infected patients.