Publications

BACKGROUND AND OBJECTIVES

HIV-associated nephropathy (HIVAN) is well described, but the clinical features of a group of renal pathologies characterized by Ig or immune complex depositions referred to as HIV-associated immune complex kidney disease (HIVICK) have not been well established. The objective of this study is to assess risk factors for HIVICK compared with contemporaneous control participants.

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS

A nested case-control study of 751 HIV-infected patients followed from January 1996 to June 2010 was conducted. Groups were compared using the chi-squared test or rank-sum analysis. Conditional logistic regression was used to estimate odds ratios (ORs) for HIVICK. Incidences of overall ESRD and with/without combined antiretroviral therapy (cART) exposure were calculated.

RESULTS

HIVICK patients were predominantly African American (92%). Compared with matched controls, patients with HIVICK were more likely to have HIV RNA >400 copies/ml (OR, 2.5; 95% confidence interval [95% CI], 1.2 to 5.2), diabetes (OR, 2.8; 95% CI, 1.1 to 6.8), and hypertension (OR, 2.3; 95% CI, 1.2 to 4.5). Compared with HIVAN, patients with HIVICK had more antiretroviral therapy exposure, lower HIV viral loads, and higher CD4 and estimated GFR. ESRD was less common in the HIVICK versus the HIVAN group (30% versus 82%; P<0.001), and the use of cART was not associated with ESRD in HIVICK patients (25% versus 26; P=0.39).

CONCLUSIONS

HIVICK was predominantly observed in African-American patients and associated with advanced HIV disease. ESRD incidence is lower in HIVICK patients compared with those with HIVAN. Unlike HIVAN, cART use was not associated with the incidence of ESRD in HIVICK.

BACKGROUND

Atopy varies by ethnicity, even within Latino groups. This variation might be due to environmental, sociocultural, or genetic factors.

OBJECTIVE

We sought to examine risk factors for atopy within a nationwide study of US Latino children with and without asthma.

METHODS

Aeroallergen skin test responses were analyzed in 1830 US Latino subjects. Key determinants of atopy included country/region of origin, generation in the United States, acculturation, genetic ancestry, and site to which subjects migrated. Serial multivariate zero-inflated negative binomial regressions stratified by asthma status examined the association of each key determinant variable with the number of positive skin test responses. In addition, the independent effect of each key variable was determined by including all key variables in the final models.

RESULTS

In baseline analyses African ancestry was associated with 3 times (95% CI, 1.62-5.57) as many positive skin test responses in asthmatic participants and 3.26 times (95% CI, 1.02-10.39) as many positive skin test responses in control participants. Generation and recruitment site were also associated with atopy in crude models. In final models adjusted for key variables, asthmatic patients of Puerto Rican (exp[β] [95% CI], 1.31 [1.02-1.69]) and mixed (exp[β] [95% CI], 1.27 [1.03-1.56]) ethnicity had a greater probability of positive skin test responses compared with Mexican asthmatic patients. Ancestry associations were abrogated by recruitment site but not region of origin.

CONCLUSIONS

Puerto Rican ethnicity and mixed origin were associated with degree of atopy within US Latino children with asthma. African ancestry was not associated with degree of atopy after adjusting for recruitment site. Local environment variation, represented by site, was associated with degree of sensitization.

IMPORTANCE

Randomized trials of implantable cardioverter-defibrillators (ICDs) for primary prevention predominantly used single-chamber devices. In clinical practice, patients often receive dual-chamber ICDs, even without clear indications for pacing. The outcomes of dual- vs single-chamber devices are uncertain.

OBJECTIVE

To compare outcomes of single- and dual-chamber ICDs for primary prevention of sudden cardiac death.

DESIGN, SETTING, AND PARTICIPANTS

Retrospective cohort study of admissions in the National Cardiovascular Data Registry's (NCDR) ICD registry from 2006-2009 that could be linked to Centers for Medicare & Medicaid Services fee-for-service Medicare claims data. Patients were included if they received an ICD for primary prevention and did not have a documented indication for pacing.

MAIN OUTCOMES AND MEASURES

Adjusted risks of 1-year mortality, all-cause readmission, heart failure readmission, and device-related complications within 90 days were estimated with propensity-score matching based on patient, clinician, and hospital factors.

RESULTS

Among 32,034 patients, 12,246 (38%) received a single-chamber device and 19,788 (62%) received a dual-chamber device. In a propensity-matched cohort, rates of complications were lower for single-chamber devices (3.51% vs 4.72%; P < .001; risk difference, -1.20 [95% CI, -1.72 to -0.69]), but device type was not significantly associated with 1-year mortality (unadjusted rate, 9.85% vs 9.77%; hazard ratio [HR], 0.99 [95% CI, 0.91 to 1.07]; P = .79), 1-year all-cause hospitalization (unadjusted rate, 43.86% vs 44.83%; HR, 1.00 [95% CI, 0.97-1.04]; P = .82), or hospitalization for heart failure (unadjusted rate, 14.73% vs 15.38%; HR, 1.05 [95% CI, 0.99-1.12]; P = .19).

CONCLUSIONS AND RELEVANCE

Among patients receiving an ICD for primary prevention without indications for pacing, the use of a dual-chamber device compared with a single-chamber device was associated with a higher risk of device-related complications and similar 1-year mortality and hospitalization outcomes. Reasons for preferentially using dual-chamber ICDs in this setting remains unclear.

Patient-provider relationships influence diabetes care; less is known about their impact on online patient portal use. Diabetes patients rated provider communication and trust. In this study, we linked responses to electronic medical record data on being a registered portal user and using secure messaging (SM). We specified regression models to evaluate main effects on portal use, and subgroup analyses by race/ethnicity and age. 52% of subjects were registered users; among those, 36% used SM. Those reporting greater trust were more likely to be registered users (relative  risk (RR)=1.14) or SM users (RR=1.29). In subgroup analyses, increased trust was associated with being a registered user among white, Latino, and older patients, as well as SM use among white patients. Better communication ratings were also related to being a registered user among older patients. Since increased trust and communication were associated with portal use within subgroups, this suggests that patient-provider relationships encourage portal engagement.

RATIONALE

Lung infections caused by opportunistic or virulent pathogens are a principal cause of morbidity and mortality in HIV infection. It is unknown whether HIV infection leads to changes in basal lung microflora, which may contribute to chronic pulmonary complications that increasingly are being recognized in individuals infected with HIV.

OBJECTIVES

To determine whether the immunodeficiency associated with HIV infection resulted in alteration of the lung microbiota.

METHODS

We used 16S ribosomal RNA targeted pyrosequencing and shotgun metagenomic sequencing to analyze bacterial gene sequences in bronchoalveolar lavage (BAL) and mouths of 82 HIV-positive and 77 HIV-negative subjects.

MEASUREMENTS AND MAIN RESULTS

Sequences representing Tropheryma whipplei, the etiologic agent of Whipple's disease, were significantly more frequent in BAL of HIV-positive compared with HIV-negative individuals. T. whipplei dominated the community (>50% of sequence reads) in 11 HIV-positive subjects, but only 1 HIV-negative individual (13.4 versus 1.3%; P = 0.0018). In 30 HIV-positive individuals sampled longitudinally, antiretroviral therapy resulted in a significantly reduced relative abundance of T. whipplei in the lung. Shotgun metagenomic sequencing was performed on eight BAL samples dominated by T. whipplei 16S ribosomal RNA. Whole genome assembly of pooled reads showed that uncultured lung-derived T. whipplei had similar gene content to two isolates obtained from subjects with Whipple's disease.

CONCLUSIONS

Asymptomatic subjects with HIV infection have unexpected colonization of the lung by T. whipplei, which is reduced by effective antiretroviral therapy and merits further study for a potential pathogenic role in chronic pulmonary complications of HIV infection.

RATIONALE

Results from 16S rDNA-encoding gene sequence-based, culture-independent techniques have led to conflicting conclusions about the composition of the lower respiratory tract microbiome.

OBJECTIVES

To compare the microbiome of the upper and lower respiratory tract in healthy HIV-uninfected nonsmokers and smokers in a multicenter cohort.

METHODS

Participants were nonsmokers and smokers without significant comorbidities. Oral washes and bronchoscopic alveolar lavages were collected in a standardized manner. Sequence analysis of bacterial 16S rRNA-encoding genes was performed, and the neutral model in community ecology was used to identify bacteria that were the most plausible members of a lung microbiome.

MEASUREMENTS AND MAIN RESULTS

Sixty-four participants were enrolled. Most bacteria identified in the lung were also in the mouth, but specific bacteria such as Enterobacteriaceae, Haemophilus, Methylobacterium, and Ralstonia species were disproportionally represented in the lungs compared with values predicted by the neutral model. Tropheryma was also in the lung, but not the mouth. Mouth communities differed between nonsmokers and smokers in species such as Porphyromonas, Neisseria, and Gemella, but lung bacterial populations did not.

CONCLUSIONS

This study is the largest to examine composition of the lower respiratory tract microbiome in healthy individuals and the first to use the neutral model to compare the lung to the mouth. Specific bacteria appear in significantly higher abundance in the lungs than would be expected if they originated from the mouth, demonstrating that the lung microbiome does not derive entirely from the mouth. The mouth microbiome differs in nonsmokers and smokers, but lung communities were not significantly altered by smoking.

OBJECTIVE

We examined the short-term and long-term associations of serum albumin with mortality and cardiovascular disease among HIV-infected veterans.

DESIGN

Retrospective cohort analysis using a national database of US veterans with HIV infection.

METHODS

This analysis evaluated all HIV-infected veterans in the Department of Veterans Affairs HIV Clinical Case Registry (CCR), a national database consisting of demographic, clinical, laboratory, pharmaceutical, and viral status data. There were 25 522 patients enrolled between 1986 and 2007. We evaluated the associations of baseline and time-updated serum albumin levels with all-cause mortality, atherosclerotic cardiovascular disease, and heart failure by multivariate proportional hazards models.

RESULTS

Over 21 years, there were 10 869 deaths; the cumulative mortality was 73.2 per 1000 person-years. After multivariate adjustment for covariates measured at baseline, the lowest category of serum albumin (<2.5 g/dl) was associated with a higher mortality risk compared with the highest category (>4 g/dl; hazard ratio 3.00; 2.67-3.37). When analyzed as a time-dependent model, the association strengthened substantially (15.1; 14.0-16.4). Findings were similar for atherosclerotic cardiovascular disease and heart failure. We stratified the baseline mortality model by year of follow-up and found that albumin was more strongly associated with deaths that occurred within 1 year of baseline (9.29; 7.85-11.0) than in the second (1.66; 1.18-2.33) or third (1.22; 0.77-1.96) year after measurement.

CONCLUSION

Among ambulatory HIV-infected patients, lower serum albumin levels are strongly predictive of mortality risk, particularly within 1 year.

BACKGROUND

The genes FTO and GNB3 are implicated in essential hypertension but their interaction remains to be explored. This study investigates the role of interaction between the two genes in the pathophysiology of essential hypertension.

METHODS/PRINCIPAL FINDINGS

In a case-control study comprising 750 controls and 550 patients, interaction between the polymorphisms of FTO and GNB3 was examined using multifactor dimensionality reduction (MDR). The influence of interaction on clinical phenotypes like systolic and diastolic blood pressure, mean arterial pressure and body mass index was also investigated. The 3-locus MDR model comprising FTO rs8050136C/A and GNB3 rs1129649T/C and rs5443C/T emerged as the best disease conferring model. Moreover, the interacted-genotypes having either 1, 2, 3, 4 or 5 risk alleles correlated with linearly increasing odds ratios of 1.91 (P = 0.027); 3.93 (P = 2.08E-06); 4.51 (P = 7.63E-07); 7.44 (P = 3.66E-08) and 11.57 (P = 1.18E-05), respectively, when compared with interacted-genotypes devoid of risk alleles. Furthermore, interactions among haplotypes of FTO (H1-9) and GNB3 (Ha-d) differed by >1.5-fold for protective-haplotypes, CTGGC+TC [H2+Ha] and CTGAC+TC [H4+Ha] (OR = 0.39, P = 0.003; OR = 0.22, P = 6.86E-05, respectively) and risk-haplotypes, AAAGC+CT [H3+Hc] and AAAGC+TT [H3+Hd] (OR = 2.91, P = 9.98E-06; OR = 2.50, P = 0.004, respectively) compared to individual haplotypes. Moreover, the effectiveness of gene-gene interaction was further corroborated with a 1.29-, 1.25- and 1.38-fold higher SBP, MAP and BMI, respectively, in patients having risk interacted-haplotype H3+Hc and 2.48-fold higher SBP having risk interacted-haplotype H3+Hd compared to individual haplotypes.

CONCLUSION

Interactions between genetic variants of FTO and GNB3 influence clinical parameters to augment hypertension.