Publications

BACKGROUND

Depression affects 20%-30% of people with HIV. Randomized controlled trials (RCTs) have demonstrated the effectiveness of interventions to improve depression among HIV-infected adults, but typically have highly selected populations which may limit generalizability. Inverse probability of sampling weights (IPSW) is a recently proposed method to transport (or standardize) findings from RCTs to a specific external target population.

METHODS

We used IPSW to transport the 6-month effect of the Measurement-Based Care (MBC) intervention on depression from the SLAM DUNC trial to a population of HIV-infected, depressed adults in routine care in the United States between 2010 and 2014.

RESULTS

In the RCT, MBC was associated with an improvement in depression at 6 months of 3.6 points on the Hamilton Depression Rating scale [95% confidence interval (CI): -5.9 to -1.3]. When IPSW were used to standardize results from the trial to the target population, the intervention effect was attenuated by 1.2 points (mean improvement 2.4 points; 95% CI: -6.1 to 1.3).

CONCLUSIONS

If implemented among HIV-infected, depressed adults in routine care, MBC may be less effective than in the RCT but can still be expected to reduce depression. Attenuation of the intervention effect among adults in routine care reflects the fact that the trial enrolled a larger proportion of individuals for whom the intervention was more effective. Given the burden of depression among HIV-infected adults, more effective interventions to improve depression are urgently needed. However, examining the transportability of trial findings is essential to understand whether similar effects can be expected if interventions are scaled-up.

BACKGROUND

Poor retention in HIV care is associated with worse clinical outcomes and increased HIV transmission. We examined the relationship between self-reported alcohol use, a potentially modifiable behavior, and retention.

METHODS

A total of 9694 people living with HIV from 7 participating US HIV clinical sites (the Centers for AIDS Research Network of Integrated Clinical Systems) contributed 23,225 observations from January 2011 to June 2014. The retention outcomes were (1) Institute of Medicine (IOM) retention: 2 visits within 1 year at least 90 days apart and (2) visit adherence [proportion of kept visits/(scheduled + kept visits)]. Alcohol use was measured with Alcohol Use Disorders Identification Test-C, generating drinking (never, moderate, and heavy) and binge frequency (never, monthly/less than monthly, weekly/daily) categories. Adjusted multivariable logistic models, accounting for repeat measures, were generated.

RESULTS

Of our sample, 82% was men, 46% white, 35% black, and 14% Hispanic. At first assessment, 37% of participants reported never drinking, 38% moderate, and 25% heavy, and 89% of the patients were retained (IOM retention measure). Participants' mean (SD) visit adherence was 84% (25%). Heavy alcohol use was associated with inferior IOM-defined retention (adjusted odds ratio 0.78, 95% confidence interval: 0.69 to 0.88), and daily/weekly binge drinking was associated with lower visit adherence (adjusted odds ratio = 0.90, 95% confidence interval: 0.82 to 0.98).

CONCLUSIONS

Both heavy drinking and frequent binge drinking were associated with worse retention in HIV care. Increased identification and treatment of heavy and binge drinking in HIV clinical care settings may improve retention in HIV care, with downstream effects of improved clinical outcomes and decreased HIV transmission.

OBJECTIVE

The Rheumatology Informatics System for Effectiveness (RISE) is a national electronic health record (EHR)-enabled registry. RISE passively collects data from EHRs of participating practices, provides advanced quality measurement and data analytic capacities, and fulfills national quality reporting requirements. Here we report the registry's architecture and initial data, and we demonstrate how RISE is being used to improve the quality of care.

METHODS

RISE is a certified Centers for Medicare and Medicaid Services Qualified Clinical Data Registry, allowing collection of data without individual patient informed consent. We analyzed data between October 1, 2014 and September 30, 2015 to characterize initial practices and patients captured in RISE. We also analyzed medication use among rheumatoid arthritis (RA) patients and performance on several quality measures.

RESULTS

Across 55 sites, 312 clinicians contributed data to RISE; 72% were in group practice, 21% in solo practice, and 7% were part of a larger health system. Sites contributed data on 239,302 individuals. Among the subset with RA, 34.4% of patients were taking a biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD) at their last encounter, and 66.7% were receiving a nonbiologic DMARD. Examples of quality measures include that 55.2% had a disease activity score recorded, 53.6% a functional status score, and 91.0% were taking a DMARD in the last year.

CONCLUSION

RISE provides critical infrastructure for improving the quality of care in rheumatology and is a unique data source to generate new knowledge. Data validation and mapping are ongoing and RISE is available to the research and clinical communities to advance rheumatology.

OBJECTIVE

Numerous factors can impede or facilitate patients' medication decision-making and adherence to physicians' recommendations. Little is known about how patients and physicians jointly view issues that affect the decision-making process. Our objective was to derive an empirical framework of patient-identified facilitators to lupus medication decision-making from key stakeholders (including 15 physicians, 5 patients/patient advocates, and 8 medical professionals) using a patient-centered cognitive mapping approach.

METHODS

We used nominal group patient panels to identify facilitators to lupus treatment decision-making. Stakeholders independently sorted the identified facilitators (n = 98) based on their similarities and rated the importance of each facilitator in patient decision-making. Data were analyzed using multidimensional scaling and hierarchical cluster analysis.

RESULTS

A cognitive map was derived that represents an empirical framework of facilitators for lupus treatment decisions from multiple stakeholders' perspectives. The facilitator clusters were 1) hope for a normal/healthy life, 2) understand benefits and effectiveness of taking medications, 3) desire to minimize side effects, 4) medication-related data, 5) medication effectiveness for "me," 6) family focus, 7) confidence in physician, 8) medication research, 9) reassurance about medication, and 10) medication economics.

CONCLUSION

Consideration of how different stakeholders perceive the relative importance of lupus medication decision-making clusters is an important step toward improving patient-physician communication and effective shared decision-making. The empirically derived framework of medication decision-making facilitators can be used as a guide to develop a lupus decision aid that focuses on improving physician-patient communication.

It has long been known that aging, at both the cellular and organismal levels, contributes to the development and progression of the pathology of many chronic diseases. However, much less research has examined the inverse relationship-the contribution of chronic diseases and their treatments to the progression of aging-related phenotypes. Here, we discuss the impact of three chronic diseases (cancer, HIV/AIDS, and diabetes) and their treatments on aging, putative mechanisms by which these effects are mediated, and the open questions and future research directions required to understand the relationships between these diseases and aging.

OBJECTIVES

We sought to describe blood pressure (BP) changes after antiretroviral therapy (ART) initiation and evaluate the association of markers of inflammation with incident hypertension in a cohort of HIV-infected individuals in Uganda.

METHODS

We used mixed effects linear regression to model changes in systolic BP over time among a cohort of HIV-infected individuals initiating ART in Uganda. After exclusion of participants with preexisting hypertension, we identified participants with normal BP throughout follow-up (controls) and those with elevated BP on ≥3 consecutive visits (cases). Before ART initiation, participants had testing for interleukin 6, kynurenine/tryptophan ratio, lipopolysaccharide, soluble CD14, soluble CD163, and D-dimer and those with viral suppression at 6 months during ART had repeat tests. We fit logistic regression models to estimate associations between biomarkers and risk of incident hypertension.

RESULTS

In the entire cohort, systolic BP increased by 9.6 mm Hg/yr (95% CI: 7.3 to 11.8) in the first 6 months of ART, then plateaued. Traditional factors: male gender (adjusted odds ratio (AOR) 2.76, 95% CI: 1.34 to 5.68), age (AOR 1.09, 95% CI: 1.04 to 1.13), overweight (AOR 4.48, 95% CI: 1.83 to 10.97), and a CD4 count <100 cells (AOR 3.08, 95% CI: 1.07 to 8.89) were associated with incident hypertension. After adjusting for these, D-dimer levels at month 6 were inversely associated with incident hypertension (AOR 0.61, 95% CI: 0.37 to 0.99). Although not significant, similar associations were seen with sCD14 and kynurenine/tryptophan ratio.

CONCLUSION

BP increases early after ART initiation in Ugandans. Traditional risk factors, rather than immune activation, were associated with incident hypertension in this population.

BACKGROUND

Asthma disproportionately affects minority populations and is associated with psychosocial stress such as racial/ethnic discrimination. We aimed to examine the association of perceived discrimination with asthma and poor asthma control in African American and Latino youth.

METHODS

We included African American (n = 954), Mexican American (n = 1,086), other Latino (n = 522), and Puerto Rican Islander (n = 1,025) youth aged 8 to 21 years from the Genes-Environments and Admixture in Latino Americans study and the Study of African Americans, Asthma, Genes, and Environments. Asthma was defined by physician diagnosis, and asthma control was defined based on the National Heart, Lung, and Blood Institute guidelines. Perceived racial/ethnic discrimination was assessed by the Experiences of Discrimination questionnaire, with a focus on school, medical, and public settings. We examined the associations of perceived discrimination with each outcome and whether socioeconomic status (SES) and global African ancestry modified these associations.

RESULTS

African American children reporting any discrimination had a 78% greater odds of experiencing asthma (OR, 1.78; 95% CI, 1.33-2.39) than did those not reporting discrimination. Similarly, African American children faced increased odds of poor asthma control with any experience of discrimination (OR, 1.97; 95% CI, 1.42-2.76) over their counterparts not reporting discrimination. These associations were not observed among Latino children. We observed heterogeneity of the association between reports of discrimination and asthma according to SES, with reports of discrimination increasing the odds of having asthma among low-SES Mexican American youth (interaction P = .01) and among high-SES other Latino youth (interaction P = .04).

CONCLUSIONS

Perceived discrimination is associated with increased odds of asthma and poorer control among African American youth. SES exacerbates the effect of perceived discrimination on having asthma among Mexican American and other Latino youth.

Natural products (NPs) are compounds that are derived from natural sources such as plants, animals, and micro-organisms. Therapeutics has benefited from numerous drug classes derived from natural product sources. The Biopharmaceutics Drug Disposition Classification System (BDDCS) was proposed to serve as a basis for predicting the importance of transporters and enzymes in determining drug bioavailability and disposition. It categorizes drugs into one of four biopharmaceutical classes according to their water solubility and extent of metabolism. The present paper reviews 109 drugs from natural product sources: 29% belong to class 1 (high solubility, extensive metabolism), 22% to class 2 (low solubility, extensive metabolism), 40% to class 3 (high solubility, poor metabolism), and 9% to class 4 (low solubility, poor metabolism). Herein we evaluated the characteristics of NPs in terms of BDDCS class for all 109 drugs as wells as for subsets of NPs drugs derived from plant sources as antibiotics. In the 109 NPs drugs, we compiled 32 drugs from plants, 50% (16) of total in class 1, 22% (7) in class 2 and 28% (9) in class 3, none found in class 4; Meantime, the antibiotics were found 5 (16%) in class 2, 22 (71%) in class 3, and 4 (13%) in class 4; no drug was found in class 1. Based on this classification, we anticipate BDDCS to serve as a useful adjunct in evaluating the potential characteristics of new natural products.

PURPOSE

The management of advanced or recurrent prostate cancer is limited in part by the lack of effective imaging agents. Metabolic changes in prostate cancer have previously been exploited for imaging, culminating in the recent US FDA approval of [C]choline for the detection of subclinical recurrent disease after definitive local therapy. Despite this milestone, production of [C]choline requires an on-site cyclotron, limiting the scope of medical centers at which this scan can be offered. In this pilot study, we tested whether prostate cancer could be imaged with positron emission tomography (PET) using [Ga]citrate, a radiotracer that targets iron metabolism but is produced without a cyclotron.

PROCEDURES

Eight patients with castrate-resistant prostate cancer were enrolled in this single-center feasibility study. All patients had evidence of metastatic disease by standard of care imaging [X-ray computed tomography (CT), bone scan, or magnetic resonance imaging (MRI)] prior to PET with [Ga]citrate. Patients were intravenously injected with increasing doses of [Ga]citrate (136.9 to a maximum of 259 MBq). Uptake time was steadily increased from 1 h to approximately 3.5 h for the final 4 patients, and all patients were imaged with a PET/MRI. Qualitative and semi-quantitative (maximum standardized uptake value (SUV)) assessment of the metastatic lesions was performed and compared to the standard of care imaging.

RESULTS

At 1- and 2-h imaging times post injection, there were no detectable lesions with [Ga]citrate PET. At 3- to 4-h uptake time, there were a total of 71 [Ga]citrate-positive lesions (67 osseous, 1 liver, and 3 lymph node). Of these, 65 lesions were visible on the standard of care imaging (CT and/or bone scan). One PET-avid osseous vertebral body metastasis was not apparent on either CT or bone scan. Twenty-five lesions were not PET-avid but seen on CT and bone scan (17 bone, 6 lymph node, 1 pleural, and 1 liver). The average of the maximum SUVs for bone or soft tissue metastases for patients treated at higher doses and uptake time was statistically higher than the corresponding parameter in normal liver, muscle, and bone. Visually obvious blood pool activity was observed even 3-4 h post injection, suggesting that further optimization of the [Ga]citrate imaging protocol is required to maximize signal-to-background ratios.

CONCLUSIONS

Our preliminary results support that PET with [Ga]citrate may be a novel tool for imaging prostate cancer. Future studies are needed to determine the optimal imaging protocol, the clinical significance of [Ga]citrate uptake, and its role in therapeutic decisions.