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1.  Tumor-Associated Macrophages Are a Useful Biomarker to Predict Recurrence After Surgical Resection of Non-Functional Pancreatic Neuroendocrine Tumors 
Annals of surgery  2014;260(6):1088-1094.
PMCID: PMC4312612  PMID: 25389924
pancreatic neoplasm; neuroendocrine tumors; tumor-associated macrophages; Ki-67 index
2.  Association of Recent Incarceration with Traumatic Injury, Substance Use Related Health Consequences, and Health Care Utilization 
Journal of addiction medicine  2014;8(1):66-72.
The higher risk of death among recently released inmates relative to the general population may be due to the higher prevalence of substance dependence among inmates or an independent effect of incarceration. We explored the effects of recent incarceration on health outcomes that may be intermediate markers for mortality.
Longitudinal multivariable regression analysis were conducted on interview data (baseline, 3, 6, and 12 month follow-up) from alcohol and/or drug dependent individuals (n=553) participating in a randomized clinical trial to test the effectiveness of chronic disease management for substance dependence in primary care. The main independent variable was recent incarceration (spending ≥1 night in jail or prison in the past 3 months). The three main outcomes of this study were: any traumatic injury; substance use-related health consequences; and health care utilization defined as hospitalization (excluding addiction treatment or detoxification) and/or emergency department visit.
Recent incarceration was not significantly associated with traumatic injury (adjusted odds ratio (AOR=0.98, 95%CI 0.65–1.49) or health care utilization (AOR=0.88, 95%CI: 0.64–1.20). However, recent incarceration was associated with higher odds for substance use-related health consequences (AOR=1.42, 95% CI: 1.02–1.98).
Among people with alcohol and/or drug dependence, recent incarceration was significantly associated with substance use-related health consequences but not injury or health care utilization after adjustment for covariates. These findings suggest that substance use related health consequences may be part of the explanation for the increased risk of death faced by former inmates.
PMCID: PMC3962184  PMID: 24365804
Incarceration; substance dependence; trauma; health care utilization
3.  Does experiencing homelessness affect women’s motivation to change alcohol or drug use?? 
Background and Objectives
Homeless women are at high risk of drug and alcohol dependence and may receive less opportunity for treatment. Our objective was to examine the association between experiencing homelessness and motivation to change drug or alcohol use.
Women (n=154) participants in a study of substance dependence at an urban medical center (69 with some homeless days in the last 90 days; 85 continuously housed at baseline) completed 6 items rating motivation to change alcohol or drug use (i.e., importance, readiness, and confidence) at baseline and in 3, 6, and 12-month follow up interviews. Unadjusted, and longitudinal analyses controlling for covariates (e.g., demographics, insurance status, substance use consequences, mental health status, and participation in treatment), were conducted.
There were no significant differences between women experiencing homeless days versus continuously housed women in the odds of reporting high motivation to change alcohol or drug use, either in unadjusted baseline analyses or longitudinal analyses adjusted for covariates. Covariates that were significantly associated with high importance, readiness or confidence to change behavior were higher life time consequences of substance use, and participation in 12-step programs.
Discussion and Conclusions
The findings suggest that clinicians should not make assumptions that homeless women have low motivation to change their substance use.
Scientific Significance and Future Directions
The same opportunities for addiction treatment should be offered to homeless as to housed women.
PMCID: PMC3857556  PMID: 24313245
Women; Homelessness; Motivation to Change; Alcohol Dependence; Drug Dependence
4.  No Detectable Association Between Frequency of Marijuana Use and Health or Healthcare Utilization Among Primary Care Patients Who Screen Positive for Drug Use 
Marijuana is the most commonly used illicit drug, yet its impact on health and healthcare utilization has not been studied extensively.
To assess the cross-sectional association between frequency of marijuana use and healthcare utilization (emergency department and hospitalization) and health (comorbidity, health status), we studied patients in an urban primary care clinic who reported any recent (past 3-month) drug use (marijuana, opioids, cocaine, others) on screening. Frequency of marijuana use in the past 3 months was the main independent variable [daily/ almost daily, less than daily and no use (reference group)]. Outcomes assessed were past 3-month emergency department or hospital utilization, the presence of medical comorbidity (Charlson index ≥ 1), and health status with the EuroQol. We used separate multivariable regression models adjusting for age, sex, tobacco and other substance use.
All 589 participants reported recent drug use: marijuana 84 % (29 % daily, 55 % less than daily), cocaine 25 %, opioid 23 %, other drugs 8 %; 58 % reported exclusive marijuana use. Frequency of marijuana use was not significantly associated with emergency department use {adjusted odds ratio [AOR] 0.67, [95 % confidence interval (CI) 0.36, 1.24] for daily; AOR 0.69 [95 % CI 0.40,1.18] for less than daily versus no use}, hospitalization [AOR 0.79 (95 % CI 0.35, 1.81) for daily; AOR 1.23 (95 % CI 0.63, 2.40) for less than daily versus no use], any comorbidity [AOR 0.62, (95 % CI 0.33, 1.18) for daily; AOR 0.67 (95 % CI 0.38, 1.17) for less than daily versus no use] or health status (adjusted mean EuroQol 69.1, 67.8 and 68.0 for daily, less than daily and none, respectively, global p = 0.78).
Among adults in primary care who screen positive for any recent illicit or non-medical prescription drug use, we were unable to detect an association between frequency of marijuana use and health, emergency department use, or hospital utilization.
PMCID: PMC3889953  PMID: 24048656
marijuana; primary care; health status; health service utilization
5.  Chronic Hepatitis C Virus Infection is Associated with All-Cause and Liver-Related Mortality in a Cohort of HIV-Infected Patients with Alcohol Problems 
Addiction (Abingdon, England)  2013;109(1):62-70.
To assess the association between hepatitis C virus (HCV) infection and overall and liver-related death in human immunodeficiency virus (HIV)-infected patients with alcohol problems.
We analyzed data from a cohort of HIV-infected adults with current or past alcohol problems enrolled between 2001 and 2003, searching for causes of death until 2010 using the National Death Index.
Setting and participants
Participants were HIV-infected adults with current or past alcohol problems, recruited in Boston, MA from HIV clinics at two hospitals, homeless shelters, drug treatment programs, subject referrals, flyers, and another cohort study with comparable recruitment sites.
The primary and secondary outcomes were all-cause and liver-related mortality, respectively. The main independent variable was HCV RNA status (positive vs. negative). Mortality rates and Kaplan-Meier survival curves were calculated by HCV status for both overall and liver-related mortality. Cox proportional hazards models were used to assess the association between HCV infection and overall and liver-related death, adjusting for alcohol and drug use over time.
397 adults (50% HCV-infected) were included. As of December 31, 2009, 83 cohort participants had died (60 HCV-infected, 23 HCV-uninfected; log rank test p<0.001), and 26 of those deaths were liver-related (21 HCV-infected, 5 HCV-uninfected; log rank test p<0.001). All-cause and liver-related mortality rates were 4.68 and 1.64 deaths per 100 person-years for HCV-infected patients and 1.65 and 0.36 per 100 person-years for those without HCV, respectively. In the fully adjusted Cox model, HCV infection was associated with both overall [HR 2.55 (95%CI:1.50–4.33), p<0.01], and liver-related mortality [HR 3.24 (95%CI:1.18–8.94), p=0.02].
Hepatitis C virus infection is independently associated with all-cause and liver-related mortality in human immunodeficiency virus-infected patients with alcohol problems, even when accounting for alcohol and other drug use.
PMCID: PMC3947001  PMID: 24112091
6.  Is cannabis use associated with HIV drug and sex risk behaviors among Russian HIV-infected risky drinkers? 
Drug and alcohol dependence  2013;132(0):74-80.
While cannabis use has been associated with increased HIV drug and sex risk behaviors, its impact on risk behaviors among HIV-infected individuals has not yet been established.
This study examined data from Russian HIV-infected risky drinkers enrolled in a randomized controlled trial of a behavioral intervention. The primary independent variable was cannabis use (current [past 30 days use], recent past [use but not in past 30 days] vs. no past year use). Primary outcomes were needle sharing and number of unprotected sexual episodes. Secondary outcomes were drug injection, number of injections, and multiple sex partners. Longitudinal regression analyses controlled for age, gender, marital status, education, CD4 count, ART use, risky alcohol use, other drug use, depressive symptoms and randomization group.
Cannabis use was common with 20% current and 26% recent past use at baseline. In longitudinal analyses current, but not recent past, cannabis consumption was significantly associated with needle sharing (AOR 2.23 current vs. none, 95% CI: 1.46, 3.36), drug injection (AOR 3.05 current vs. none, 95% CI: 2.06, 4.53) and number of injections (adjusted IRR 1.50 current vs. none, 95% CI: 1.19, 1.89). Current and recent past cannabis use were significantly associated with multiple sex partners but not with number of unprotected sex episodes.
Cannabis use was associated with drug and sex risk behaviors among Russian HIV-infected risky drinkers. Inquiry about cannabis use among HIV-infected patients may reveal a patient group at higher risk for sex and drug use behaviors that lead to HIV transmission.
PMCID: PMC3726566  PMID: 23410616
Cannabis use; HIV; sex risk behavior; drug risk behavior; Russia
7.  Impact of lifetime alcohol use on liver fibrosis in a population of HIV-infected patients with and without hepatitis C coinfection 
The effect of alcohol on liver disease in HIV infection has not been well characterized.
We performed a cross-sectional multivariable analysis of the association between lifetime alcohol use and liver fibrosis in a longitudinal cohort of HIV-infected patients with alcohol problems. Liver fibrosis was estimated with two non-invasive indices, “FIB-4”, which includes platelets, liver enzymes, and age; and “APRI”, which includes platelets and liver enzymes. FIB-4<1.45 and APRI<0.5 defined absence of liver fibrosis. FIB-4>3.25 and APRI>1.5 defined advanced liver fibrosis. The main independent variable was lifetime alcohol consumption (<150 kg, 150–600kg, >600 kg).
Subjects (n=308) were 73% male, mean age 43 years, 49% with hepatitis C virus (HCV) infection, 60% on antiretroviral therapy, 49% with an HIV RNA load<1000 copies/mL, and 18.7% with a CD4 count<200 cells/mm3. Forty-five percent had lifetime alcohol consumption >600 kg, 32.7% 150–600 kg, and 22.3% <150 kg; 33% had current heavy alcohol use, and 69% had >9 years of heavy episodic drinking. Sixty-one percent had absence of liver fibrosis and 10% had advanced liver fibrosis based on FIB-4. In logistic regression analyses controlling for age, gender, HCV infection, and CD4 count, no association was detected between lifetime alcohol consumption and absence of liver fibrosis (FIB-4<1.45) [adjusted odds ratio (AOR)=1.12 (95%CI:0.25–2.52) for 150–600 kg versus <150 kg; AOR=1.11 (95%CI:0.52–2.36) for >600 kg vs. <150 kg; global p=0.95]. Additionally, no association was detected between lifetime alcohol use and advanced liver fibrosis (FIB-4>3.25). Results were similar using APRI, and among those with and without HCV infection.
In this cohort of HIV-infected patients with alcohol problems, we found no significant association between lifetime alcohol consumption and absence of liver fibrosis or the presence of advanced liver fibrosis, suggesting that alcohol may be less important than other known factors that promote liver fibrosis in this population.
PMCID: PMC3758457  PMID: 23647488
alcohol; HIV; Hepatitis C virus; liver fibrosis
8.  Interleukin-6 Is Associated with Noninvasive Markers of Liver Fibrosis in HIV-Infected Patients with Alcohol Problems 
AIDS Research and Human Retroviruses  2013;29(8):1110-1116.
Both HIV and hepatitis C virus (HCV) cause chronic inflammation and alterations in serum inflammatory cytokines. The impact of inflammatory cytokines on liver fibrosis is not well understood. We studied the association between interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α and liver fibrosis in HIV-infected patients with current or past alcohol problems (CAGE ≥2 or physician investigator diagnosis). Liver fibrosis was estimated with FIB-4 (FIB-4 <1.45 defined the absence of liver fibrosis and FIB-4 >3.25 defined advanced fibrosis). Logistic regression was used to assess the association between cytokines and fibrosis, adjusting for age, sex, CD4, HIV RNA, current antiretroviral therapy, body mass index, and HCV. Secondary analyses explored whether the association between HCV and liver fibrosis was mediated by these cytokines. Participants (n=308) were all HIV-infected; 73% were male with a mean age of 42 years; half had detectable HCV-RNA, 60.7% had an absence of liver fibrosis, and 10.1% had advanced fibrosis. In models that adjusted for each cytokine separately, higher levels of IL-6 were significantly associated with an absence of fibrosis [adjusted OR (95% CI): 0.43 (0.19, 0.98), p=0.05] and were borderline significant for advanced fibrosis [adjusted OR (95% CI): 8.16 (0.96, 69.54), p=0.055]. In the final model, only higher levels of IL-6 remained significantly associated with advanced liver fibrosis [adjusted OR (95% CI): 11.78 (1.17, 118.19), p=0.036]. Adjustment for inflammatory cytokines attenuated the adjusted OR for the association between HCV and fibrosis in the case of IL-6 [for the absence of fibrosis from 0.32 (0.17, 0.57) p<0.01 to 0.47 (0.23, 0.96) p=0.04; and for advanced fibrosis from 7.22 (2.01, 25.96) p<0.01 to 6.62 (1.20, 36.62) p=0.03], suggesting IL-6 may be a partial mediator of the association between HCV and liver fibrosis. IL-6 was strongly and significantly associated with liver fibrosis in a cohort of HIV-infected patients with alcohol problems. IL-6 may be a useful predictive marker for liver fibrosis for HIV-infected patients.
PMCID: PMC3715787  PMID: 23601055
9.  Punitive policing and associated substance use risks among HIV-positive people in Russia who inject drugs 
Drug law enforcement is part of the HIV risk environment among people who inject drugs (PWID). Punitive policing practices such as extrajudicial arrests for needle possession and police planting of drugs have been described anecdotally in Russia, but these experiences and their associations with risky drug behaviours have not been quantified. This study aims to quantify the burden of extrajudicial police arrests among a cohort of HIV-positive PWID in Russia and to explore its links to drug-related health outcomes.
In a cross-sectional study of 582 HIV-positive people with lifetime injection drug use (IDU) in St. Petersburg, Russia, we estimated the prevalence of self-reported extrajudicial police arrests. We used multiple logistic regression to evaluate associations between arrests and the following outcomes: overdose, recent IDU and receptive needle sharing.
This cohort's mean age was 29.8 years, 60.8% were male; 75.3% reported non-fatal drug overdose, 50.3% recent IDU and 47.3% receptive needle sharing. Extrajudicial arrests were reported by more than half (60.5%, 95% confidence interval [CI]: 56.5–64.5) and were associated with higher odds of non-fatal drug overdose (AOR 1.52, 95% CI: 1.02–2.25) but not with recent IDU (AOR 1.17, arrests were associated with receptive needle sharing (AOR 1.84, 95% CI: 1.09–3.09).
Extrajudicial police arrests were common among this cohort of Russian HIV-positive PWID and associated with non-fatal overdose and, among those with recent IDU, receptive needle sharing. As a part of the HIV risk environment of PWIDs, these practices might contribute to HIV transmission and overdose mortality. Further research is needed to relate these findings to the operational environment of law enforcement and to better understand how police interventions among PWIDs can improve the HIV risk environment.
PMCID: PMC4093768  PMID: 25014321
human rights; police involvement; PLHA; injection drug use; key populations; Russian Federation
10.  Pain is Associated with Heroin Use over Time in HIV-Infected Russian Drinkers 
Addiction (Abingdon, England)  2013;108(10):1779-1787.
This study evaluated whether pain was associated with increased risk of using heroin, stimulants or cannabis among HIV-infected drinkers in Russia.
Secondary analysis of longitudinal data from the HERMITAGE study, a behavioral randomized controlled trial, with data collected at baseline, 6 month and 12 month visits.
Recruitment occurred at HIV and addiction treatment sites in St. Petersburg, Russian Federation.
Six-hundred and ninety-nine HIV-infected adult drinkers.
The primary outcome was past month illicit drug use; secondary outcomes examined each drug (heroin, stimulants and cannabis) separately. The main predictor was pain that at least moderately interfered with daily living. General estimating equations (GEE) logistic regression models were used to evaluate the association between pain and subsequent illicit drug use adjusting for potential confounders.
Participants reporting pain appeared to have higher odds of using illicit drugs, although the results did not reach statistical significance (adjusted Odds Ratio [OR]=1.32; 95% CI: 0.99, 1.76, p=0.06). There was a significant association between pain and heroin use (OR=1.54; 95% CI: 1.11 to 2.15, p=0.01) but not other drugs (OR=0.75; 95% CI: 0.40 to 1.40, p=0.35 for stimulants and OR=0.70; 95% CI: 0.45 to 1.07, p=0.09 for cannabis).
HIV-infected Russian drinkers who reported pain were more likely to use heroin over time. Pain may be an unrecognized risk factor for persistent heroin use with implications for HIV transmission in Russia.
PMCID: PMC4012755  PMID: 23773361
Pain; HIV; substance use; heroin
11.  Associations between Partner Violence Perpetration and History of STI among HIV-infected Substance Using Men in Russia 
AIDS care  2012;25(5):646-651.
Studies document a significant association between victimization from intimate partner violence (IPV) and sexually transmitted infections (STI) and HIV among substance using women in Russia and elsewhere, but no study has examined IPV perpetration and STI among Russian men or HIV-infected men in Eastern Europe. This study was designed to assess the association between lifetime history of IPV perpetration and STI (lifetime and current) among substance using HIV-infected men in Russia. Cross-sectional analyses were conducted with baseline data from 415 male participants enrolled in a randomized HIV intervention clinical trial [the HERMITAGE Study]. Participants were HIV-infected men reporting recent heavy alcohol use and unprotected sex in St. Petersburg, Russia. Baseline surveys assessed demographics, IPV perpetration, risk behaviors, and STI history. Current STI was assessed via blood testing for syphilis and urine testing for gonorrhea, Chlamydia and trichomonas. Multiple logistic regression analyses were used to assess the association between history of IPV with lifetime and current STI. Participants were aged 20–57 years. Almost half of participants (46%) reported a history of IPV perpetration; 81% reported past 30-day binge alcohol use, and 43% reported past 30-day injection drug use. Past and current STI was 41% and 12%, respectively. Men reporting a history of IPV perpetration had significantly higher odds of reporting ever having an STI (AOR=1.6, 95% CI=1.1, 2.4) but lower odds of testing positive for a current STI (AOR=0.50, 95% CI=0.26, 0.96). These findings demonstrate that a history of male IPV perpetration is common in HIV-infected Russian men and associated with a history of STI. Programmatic work toward IPV prevention is needed in Russia and may be beneficial in mitigating STIs, but more research is needed to understand how and why the association between IPV and STI changes over time in this population.
PMCID: PMC3582729  PMID: 22971088
12.  Chronic Care Management for Dependence on Alcohol and Other Drugs: The AHEAD Randomized Trial 
People with substance dependence have health consequences, high healthcare utilization and frequent comorbidity but often receive poor quality care overall and for dependence. Chronic care management has been proposed as an approach to improve care and outcomes.
To determine whether chronic care management (CCM) for alcohol and other drug (AOD) dependence improves substance use outcomes compared to usual primary care.
Design, Setting, and Participants
The AHEAD study was a randomized trial in people with AOD dependence, not necessarily seeking treatment, at a Boston hospital-based primary care practice. Of the 655 eligible participants, 563 (86%) were randomized. Study participants were recruited from September 2006 to September 2008 from a free-standing residential detoxification unit (74%) and referrals from an urban teaching hospital and advertisements (26%). Participants were randomized to CCM (n=282) or no CCM (n=281).
CCM included longitudinal care coordinated with a primary care clinician, motivational enhancement therapy, relapse prevention counseling, and on-site medical, addiction and psychiatric treatment, social work assistance and referrals (including mutual help). The no CCM group received a primary care appointment, and a list of treatment resources including a phone number to arrange counseling.
Main Outcome and Measure
The primary outcome was self-reported abstinence from opioids, stimulants or heavy drinking. Biomarkers were secondary outcomes. We employed longitudinal analyses for data from 3, 6 and 12 months (last interview January 21, 2010).
Of 563 participants, 95% completed 12-month follow-up. Baseline characteristics of the study participants were similar across randomization groups, but differed significantly for race and depressive symptoms. There was no significant difference in abstinence from opioids, stimulants or heavy drinking between the CCM (44%) and control (42%) groups (adjusted odds ratio 0.84; 95% confidence interval (CI) 0.65–1.10; p=0.21). No significant differences were found for secondary outcomes: addiction severity, health-related quality of life or drug problems. No subgroup effects were found except among those with alcohol dependence in whom CCM was associated with fewer alcohol problems (mean 10 vs. 13, incidence rate ratio 0.85, 95% CI 0.72–1.00, p=0.048).
Conclusions and Relevance
Among persons with AOD dependence, CCM compared with a primary care appointment but no CCM did not increase self-reported abstinence over 12 months. Whether more intensive or longer duration CCM is effective would require further investigation.
PMCID: PMC3902022  PMID: 24045740
13.  Gender-Based Disparities in Infant and Child Mortality Based on Maternal Exposure to Spousal Violence 
To examine associations between intimate partner violence (IPV) against Indian women and risk of death among their infants and children, as well as related gender-based disparities.
Analyses of nationally representative data to estimate adjusted hazard ratios (aHRs) and attributable risks for infant and child mortality based on child gender and on IPV against mothers.
Women aged 15 to 49 years (n=59 467) across all 29 Indian states participating in the Indian National Family Health Survey 3 provided information about 158 439 births and about infant and child mortality occurring during the 20 years before the survey.
Main Outcome Measures
Maternal IPV and infant and child (<5 years) mortality among boy vs girl children.
Infant mortality was greater among infants whose mothers experienced IPV (79.2 of 1000 births) vs those whose mothers did not experience IPV (59.1 of 1000 births) (aHR, 1.09; 95% confidence interval [CI], 1.03–1.15); this effect was significant only for girls (1.15; 1.07–1.24; for boys, 1.04; 0.97–1.11). Child mortality was also greater among children whose mothers experienced IPV (103.6 of 1000 births) vs those whose mothers did not experience IPV (74.8 per 1000 births) (aHR, 1.10; 95% CI, 1.05–1.15); again, this effect was significant only for girls (1.14; 1.07–1.21; for boys, 1.05; 0.99–1.12). An estimated 58 021 infant girl deaths and 89 264 girl child deaths were related to spousal violence against wives annually, or approximately 1.2 million female infant deaths and 1.8 million girl deaths in India between December 1985 and August 2005.
Intimate partner violence against women should be considered an urgent priority within programs and policies aimed at maximizing survival of children in India, particularly those attempting to increase the survival of girls 5 years and younger.
PMCID: PMC3940346  PMID: 21199976
14.  The Short Inventory of Problems—Modified for Drug Use (SIP-DU): Validity in a Primary Care Sample 
Primary care physicians can help drug-dependent patients mitigate adverse drug use consequences; instruments validated in primary care to measure these consequences would aid in this effort. This study evaluated the validity of the Short Inventory of Problems—Alcohol and Drugs modified for Drug Use (SIP-DU) among subjects recruited from a primary care clinic (n = 106). SIP-DU internal consistency was evaluated using Cronbach’s alphas, convergent validity by correlating the total SIP-DU score with the DAST-10, and construct validity by analyzing the factor structure. The SIP-DU demonstrated high internal consistency (Cronbach’s alpha for overall scale .95, subscales .72–.90) comparable with other SIP versions and correlated well with the DAST-10 (r = .70). Confirmatory factor analysis suggested an unacceptable fit of previously proposed factors; exploratory factor analyses suggested a single factor of drug use consequences. The SIP-DU offers primary care clinicians a valid and practical assessment tool for drug use consequences.
PMCID: PMC3889861  PMID: 22494228
15.  OTX2 loss causes rod differentiation defect in CRX-associated congenital blindness 
Leber congenital amaurosis (LCA) encompasses a set of early-onset blinding diseases that are characterized by vision loss, involuntary eye movement, and nonrecordable electroretinogram (ERG). At least 19 genes are associated with LCA, which is typically recessive; however, mutations in homeodomain transcription factor CRX lead to an autosomal dominant form of LCA. The mechanism of CRX-associated LCA is not understood. Here, we identified a spontaneous mouse mutant with a frameshift mutation in Crx (CrxRip). We determined that CrxRip is a dominant mutation that results in congenital blindness with nonrecordable response by ERG and arrested photoreceptor differentiation with no associated degeneration. Expression of LCA-associated dominant CRX frameshift mutations in mouse retina mimicked the CrxRip phenotype, which was rescued by overexpression of WT CRX. Whole-transcriptome profiling using deep RNA sequencing revealed progressive and complete loss of rod differentiation factor NRL in CrxRip retinas. Expression of NRL partially restored rod development in CrxRip/+ mice. We show that the binding of homeobox transcription factor OTX2 at the Nrl promoter was obliterated in CrxRip mice and ectopic expression of OTX2 rescued the rod differentiation defect. Together, our data indicate that OTX2 maintains Nrl expression in developing rods to consolidate rod fate. Our studies provide insights into CRX mutation-associated congenital blindness and should assist in therapeutic design.
PMCID: PMC3904630  PMID: 24382353
16.  Nondisclosure of HIV Infection to Sex Partners and Alcohol’s Role: A Russian Experience 
AIDS and behavior  2013;17(1):390-398.
Nondisclosure of one’s HIV infection to sexual partners obviates safer sex negotiations and thus jeopardizes HIV transmission prevention. The role of alcohol use in the disclosure decision process is largely unexplored. This study assessed the association between alcohol use and recent nondisclosure of HIV serostatus to sex partners by HIV-infected risky drinkers in St. Petersburg, Russia. Approximately half (317/605; 52.4 %) reported not having disclosed their HIV serostatus to all partners since awareness of infection. Using three separate GEE logistic regression models, we found no significant association between alcohol dependence, risky alcohol use (past 30 days), or alcohol use at time of sex (past 30 days) with recent (past 3 months) nondisclosure (AOR [95 %CI] 0.81 [0.55, 1.20], 1.31 [0.79, 2.17], 0.75 [0.54, 1.05], respectively). Alcohol use at time of sex was associated with decreased odds of recent nondisclosure among seroconcordant partners and among casual partners. Factors associated with nondisclosure were relationship with a casual partner, a serodiscordant partner, multiple sex partners, awareness of HIV diagnosis less than 1 year, and a lifetime history of sexually transmitted disease. Nondisclosure of HIV status to sex partners is common among HIV-infected Russians, however alcohol does not appear to be a predictor of recent disclosure.
PMCID: PMC3634358  PMID: 22677972
Nondisclosure; Disclosure; HIV; Russia; Alcohol
17.  Prevalence and Correlates of Non-Disclosure of HIV Serostatus to Sex partners among HIV-Infected Female Sex Workers and HIV-infected Male Clients of Female Sex Workers in India 
AIDS and behavior  2013;17(1):399-406.
This study examines non-disclosure of HIV serostatus to sex partners among HIV-infected adults involved with transactional sex in Mumbai, India. Surveys were conducted with HIV-infected female sex workers (n = 211) and infected male clients (n = 205) regarding HIV knowledge, awareness of sex partners’ HIV serostatus, alcohol use, transactional sex involvement post-HIV diagnosis and non-disclosure of HIV serostatus. Gender-stratified multiple logistic regression models were used for analysis. Non-disclosure of one’s serostatus to all sex partners was reported by almost three-fifths of females and two-fifths of males. Predictors of non-disclosure included lack of correct knowledge about HIV and no knowledge of sex partners’ HIV serostatus. Among females, recent alcohol consumption also predicted non-disclosure. Among males, 10 + paid sexual partners in the year following HIV diagnosis predicted non-disclosure. Secondary HIV prevention efforts in India require greater focus on HIV disclosure communication and integrated alcohol and sexual risk reduction.
PMCID: PMC3634359  PMID: 22810892
HIV serostatus non-disclosure; Female sex workers; Male clients; Alcohol use; India
We examinedthe effect ofthe quality of primary care-basedchronic disease management (CDM)for alcohol and/or other drug (AOD) dependenceonaddiction outcomes.We assessed qualityusing 1)avisit frequencybased measure and 2) a self-reported assessment measuring alignment with the chronic care model. The visit frequency based measure had no significant association with addiction outcomes. Theself-reported measure of care - when care was at a CDM clinic - was associated with lower drug addiction severity.The self-reported assessment of care from any healthcare source (CDM clinic or elsewhere)was associated with lower alcoholaddiction severity and abstinence.These findings suggest that high quality CDM for AOD dependence may improve addiction outcomes.Quality measuresbased upon alignment with the chronic care model may better capture features of effective CDM care than a visitfrequency measure.
PMCID: PMC3507538  PMID: 22840687
19.  Methadone Dose, Take Home Status and Hospital Admission among Methadone Maintenance Patients 
Journal of addiction medicine  2012;6(3):186-190.
Among patients receiving methadone maintenance treatment (MMT) for opioid dependence, receipt of unobserved dosing privileges (take homes) and adequate doses (i.e. ≥ 80mg) are each associated with improved addiction treatment outcomes, but the association with acute care hospitalization is unknown. We studied whether take-home dosing and adequate doses (i.e. ≥ 80 mg) were associated with decreased hospital admission among patients in a MMT program.
We reviewed daily electronic medical records of patients enrolled in one MMT program to determine receipt of take home doses, methadone dose ≥ 80mg and hospital admission date. Non-linear mixed effects logistic regression models were used to evaluate whether take home doses or dose ≥ 80mg on a given day were associated with hospital admission on the subsequent day. Covariates in adjusted models included age, gender, race/ethnicity, HIV status, medical illness, mental illness, and polysubstance use at program admission.
Subjects (n=138) had the following characteristics: mean age 43 years; 52% female; 17% HIV-infected; 32% medical illness; 40% mental illness; and 52% polysubstance use. During a mean follow-up of 20 months, 42 patients (30%) accounted for 80 hospitalizations. Receipt of take homes was associated with significantly lower odds of a hospital admission (AOR 0.26; 95%CI: 0.11-0.62), whereas methadone dose ≥ 80mg was not (AOR 1.01; 95% CI: 0.56-1.83).
Among MMT patients, receipt of take homes, but not dose of methadone, was associated with decreased hospital admission. Take home status may reflect not only patients’ improved addiction outcomes, but also reduced healthcare utilization.
PMCID: PMC3416958  PMID: 22694929
Methadone maintenance treatment; dose; take home status; hospital admission
20.  Human immunodeficiency virus, hepatitis C, and inflammatory biomarkers in individuals with alcohol problems: a cross-sectional study 
BMC Infectious Diseases  2013;13:399.
Assessing whether hepatitis C (HCV) co-infection with human immunodeficiency virus (HIV) is associated with increased inflammation is complex. The liver, integral to inflammatory biomarker synthesis, is compromised by HCV and alcohol abuse. Using single liver-synthesized biomarkers (e.g. C-reactive protein) to represent inflammation may not be appropriate in HIV/HCV co-infection. We hypothesized that 1) detectable HIV/HCV RNA was independently associated with increased inflammation; 2) a composite inflammation measure describes inflammation differently from single inflammatory biomarkers.
We compared inflammation by HIV/HCV group in a cohort of 361 HIV infected participants from the HIV-Longitudinal Interrelationships of Viruses and Ethanol study. Inflammatory biomarkers >75th percentile were considered elevated. Associations between HIV/HCV group and elevated biomarkers were analyzed as a composite measure (inflammatory burden) or individually. We defined inflammatory burden as number of concurrently elevated biomarkers. Biomarkers included interleukin-6 (IL-6), C-reactive protein (CRP), cystatin C, serum amyloid-A (SAA), tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10). Covariates: alcohol, liver fibrosis, comorbidities, CD4 count, antiretroviral therapy, substance use.
Detectable HIV and HCV RNA (OR = 2.49; 95% CI = 1.05–5.89) and detectable HCV RNA alone (2.95; 1.08–8.01) were independently associated with increased odds of having a greater inflammatory burden compared to undetectable viremia. Elevated IL-10 (7.79; 1.90–31.97) and TNF-α (7.70; 1.42–41.83) were independently associated with detectable HIV and HCV RNA. Elevated IL-10 was also associated with detectable HCV RNA alone (5.51; 1.17, 25.84).
Detectable HIV and HCV replication versus undetectable replication was associated with inflammatory burden and certain inflammatory biomarkers independently of alcohol consumption, liver fibrosis and other comorbidities.
PMCID: PMC3848623  PMID: 23987993
HIV; HCV; Inflammation; Alcohol; Liver; Comorbidity
21.  History of Intimate Partner Violence is Associated with Sex Work but not STI among HIV- positive Female Drinkers in Russia 
This paper assesses the associations between intimate partner violence (IPV) and STIs and sexual risks among HIV-positive female drinkers in St. Petersburg, Russia. Survey and STI data were analyzed from 285 women in HERMITAGE, a secondary prevention study with HIV-positive heavy drinkers. Logistic and Poisson regression analyses assessed associations of IPV with STI and risky sex. Most women (78%) experienced IPV and 19% were STI-positive; 15% sold sex. IPV was not significantly associated with STI, but was with selling sex (AOR=3.56, 95% CI=1.02–12.43). In conclusion, IPV is common and associated with sex trade involvement among Russian HIV-positive female drinkers.
PMCID: PMC3752703  PMID: 23970660
Russia; sex work; substance use; HIV-positive; sexually transmitted infections (STI); intimate partner violence (IPV)
23.  Hepatitis C Virus Infection is Associated with Painful Symptoms in HIV-infected Adults 
AIDS Care  2012;24(7):820-827.
The study aim was to assess whether HCV was associated with painful symptoms among patients with HIV. Using data from a prospective cohort of HIV-infected adults with alcohol problems we assessed the effects of HCV on pain that interfered with daily living and painful symptoms (muscle/joint pain, headache and peripheral neuropathy). Exploratory analyses assessed whether depressive symptoms and inflammatory cytokines mediated the relationship between HCV and pain. HCV-infected participants (n=200) had higher odds of pain that interfered with daily living over time (adjusted odds ratio [AOR] 1.43; 95% CI 1.02 to 2.01; p=0.04) compared to those not infected with HCV. HIV/HCV co-infected participants had higher odds of muscle or joint pain (AOR 1.45; 95% CI 1.06 to 1.97; p=0.02) and headache (AOR 1.57; 95% CI: 1.18 to 2.07; p<0.01). The association between HCV and peripheral neuropathy did not reach statistical significance (AOR 1.33; 0.96 to 1.85; p=0.09). Depressive symptoms and inflammatory cytokines did not appear to mediate the relationship between HCV and pain. Adults with HIV who are also co-infected with HCV are more likely to experience pain that interfered with daily living, muscle or joint pain, and headaches compared to those not co-infected. Research is needed to explore the association between HCV infection and pain, and to determine whether HCV treatment is an effective intervention.
PMCID: PMC3370099  PMID: 22272656
Pain; hepatitis C; cytokines; symptoms; peripheral neuropathy
24.  Substance abuse treatment utilization among adults living with HIV/AIDS and alcohol or drug problems 
A prospective cohort study to identify factors associated with receipt of substance abuse treatment (SAT) among adults with alcohol problems and HIV/AIDS. Data from the Human Immunodeficiency Virus-Longitudinal Interrelationships of Viruses and Ethanol (HIV-LIVE) study were analyzed. Generalized estimating equation logistic regression models were fit to identify factors associated with any service utilization. An alcohol dependence diagnosis had a negative association with SAT (adjusted odds ratio [AOR] = 0.36; 95% confidence interval [95% CI] = 0.19, 0.67), as did identifying as a sexual orientation other than heterosexual (AOR = 0.46; CI = 0.29, 0.72), and having social supports that use alcohol/drugs (AOR = 0.62; CI = 0.45, 0.83). Positive associations with SAT include: presence of hepatitis C antibody (AOR = 3.37; CI = 2.24, 5.06), physical or sexual abuse (AOR = 2.12; CI = 1.22, 3.69), social supports that help with sobriety (AOR = 1.92; CI = 1.28, 2.87), homelessness (AOR = 2.40; CI = 1.60, 3.62) drug dependence diagnosis (AOR = 2.64; CI = 1.88, 3.70), and clinically important depressive symptoms (AOR = 1.52, CI = 1.08, 2.15). While reassuring that factors indicating need for SAT among people with HIV and alcohol problems (e.g. drug dependence) are associated with receipt, non-need factors (e.g. sexual orientation, age) that should not decrease likelihood of receipt of treatment were identified.
PMCID: PMC3634563  PMID: 21700412
Substance abuse; treatment; addiction; HIV/AIDS; alcohol
25.  Factors associated with attendance in 12-step groups (Alcoholics Anonymous/Narcotics Anonymous) among adults with alcohol problems living with HIV/AIDS 
Drug and alcohol dependence  2010;113(2-3):165-171.
Despite the value of 12-step meetings, few studies have examined factors associated with attendance among those living with HIV/AIDS, such as the impact of HIV disease severity and demographics.
This study examines predisposing characteristics, enabling resources and need on attendance at Alcoholic Anonymous (AA) and Narcotics Anonymous (NA) meetings among those living with HIV/AIDS and alcohol problems.
Secondary analysis of prospective data from the HIV-Longitudinal Interrelationships of Viruses and Ethanol study, a cohort of 400 adults living with HIV/AIDS and alcohol problems. Factors associated with AA/NA attendance were identified using the Anderson model for vulnerable populations. Generalized estimating equation logistic regression models were fit to identify factors associated with self-reported AA/NA attendance.
At study entry, subjects were 75% male, 12% met diagnostic criteria for alcohol dependence, 43% had drug dependence and 56% reported attending one or more AA/NA meetings (past six months). In the adjusted model, female gender negatively associated with attendance, as were social support systems that use alcohol and/or drugs, while presence of HCV antibody, drug dependence diagnosis, and homelessness associated with higher odds of attendance.
Non-substance abuse related barriers to AA/NA group attendance exist for those living with HIV/AIDS, including females and social support systems that use alcohol and/or drugs. Positive associations of homelessness, HCV infection and current drug dependence were identified. These findings provide implications for policy makers and treatment professionals who wish to encourage attendance at 12-step meetings for those living with HIV/AIDS and alcohol or other substance use problems.
PMCID: PMC3603575  PMID: 20832197
HIV-infection; alcohol addiction disorder; substance-related disorders; 12 step groups; HIV/AIDS

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