Publications

OBJECTIVE

Dopamine, iron, and inflammatory pathways are considered important to the development of restless legs syndrome (RLS). Recent genetic studies support involvement of dopamine and iron; however, cytokine gene variation in the inflammatory component remains unexplored. A recent study reported a high prevalence of RLS among HIV-infected adults. We estimate occurrence of RLS in an ethnically diverse sample of HIV-infected adults and examine differences in demographic factors, clinical characteristics, and biomarkers relating to dopamine, iron, and inflammation between adults with and without RLS symptoms.

DESIGN

A prospective longitudinal study aimed at identifying biomarkers of RLS symptom experience among HIV-infected adults.

METHOD

316 HIV-positive adults were evaluated using International RLS Study Group criteria. Genes were chosen for hypothesized relationships to dopamine (NOS1, NOS2), iron (HFE) or inflammation-mediated by cytokine genes (interferon [IFN], interleukin [IL], nuclear factor kappa-B [NFKB], and tumor necrosis factor alpha [TNFA]).

RESULTS

Similar to general population estimates, 11% of the sample met all four RLS diagnostic criteria. Controlling for race, gender, and hemoglobin, carrying two copies of the minor allele for IL1B rs1143643, rs1143634, or rs1143633 or carrying the minor allele for IL17A rs8193036 was associated with increased likelihood of meeting RLS diagnostic criteria.

CONCLUSION

This study provides preliminary evidence of a genetic association between IL1B and IL17A genes and RLS.

Elucidating interrelations between prior affective experience, current affective state, and acute urge to smoke could inform affective models of addiction motivation and smoking cessation treatment development. This study tested the hypothesis that prior levels of positive (PA) and negative (NA) affect predict current smoking urge via a mediational pathway involving current state affect. We also explored if tobacco deprivation moderated affect-urge relations and compared the effects of PA and NA on smoking urge to one another. At a baseline session, smokers reported affect experienced over the preceding few weeks. At a subsequent experimental session, participants were randomly assigned to 12-hr tobacco deprived (n = 51) or nondeprived (n = 69) conditions and reported state affect and current urge. Results revealed a mediational pathway whereby prior NA reported at baseline predicted state NA at the experimental session, which in turn predicted current urge. This mediational pathway was found primarily for an urge subtype indicative of urgent need to smoke and desire to smoke for NA relief, was stronger in the deprived (vs. nondeprived) condition, and remained significant after controlling for PA. Prior PA and current state PA were inversely associated with current urge; however, these associations were eliminated after controlling for NA. These results cohere with negative reinforcement models of addiction and with prior research and suggest that: (a) NA plays a stronger role in smoking motivation than PA; (b) state affect is an important mechanism linking prior affective experience to current urge; and (c) affect management interventions may attenuate smoking urge in individuals with a history of affective disturbance.

OBJECTIVE

We report rates and risk factors for attrition in the first cohort of patients followed through all stages from HIV testing to antiretroviral therapy (ART) initiation.

DESIGN

Cohort study of all patients diagnosed with HIV between January and June 2009.

METHODS

We calculated the proportion of patients who completed CD4 cell counts and initiated ART or remained in pre-ART care during 2 years of follow-up and assessed predictors of attrition.

RESULTS

Of 1427 patients newly diagnosed with HIV, 680 (48%) either initiated ART or were retained in pre-ART care for the subsequent 2 years. One thousand eighty-three patients (76%) received a CD4 cell count, and 973 (90%) returned for result; 297 (31%) had CD4 cell count <200 cells per microliter, and of these, 256 (86%) initiated ART. Among 429 patients with CD4 >350 cells per microliter, 215 (50%) started ART or were retained in pre-ART care. Active tuberculosis was associated with not only lower odds of attrition before CD4 cell count [odds ratio (OR): 0.08; 95% confidence interval (CI): 0.03 to 0.25] but also higher odds of attrition before ART initiation (OR: 2.46; 95% CI: 1.29 to 4.71). Lower annual income (≤US $125) was associated with higher odds of attrition before CD4 cell count (OR: 1.65; 95% CI: 1.25 to 2.19) and before ART initiation among those with CD4 cell count >350 cells per microliter (OR: 1.74; 95% CI: 1.20 to 2.52). After tracking patients through a national database, the retention rate increased to only 57%.

CONCLUSIONS

Fewer than half of patients newly diagnosed with HIV initiate ART or remain in pre-ART care for 2 years in a clinic providing comprehensive services. Additional efforts to improve retention in pre-ART are critically needed.

AIM

Data from registration trials with highly selective patients have shown that hepatitis B envelope antigen (HBeAg)-positive patients with chronic hepatitis B respond well to entecavir (ETV) 0.5 mg daily, with an HBeAg seroconversion rate of 21% at 12 months. However, there are varying data on the treatment outcomes of ETV 0.5 mg daily in routine clinical settings, with seroconversion rates at 12 months ranging from 8 to 48% in studies limited to 44-90 patients from centers in Asia, Europe, and South America.

MATERIALS AND METHODS

In the present study, we examined long-term treatment efficacy and tolerability in 136 consecutive treatment-naive HBeAg-positive chronic hepatitis B patients treated between January 2005 and January 2011 with ETV 0.5 mg daily at community clinics and tertiary centers in the USA. The primary study end point was HBeAg seroconversion.

RESULTS

Sixty-one percent of HBeAg-positive patients were men, mean age 39 ± 12 years, median hepatitis B virus DNA 7.48 (3.7-9.8) log10 IU/ml, median alanine aminotransferase 67 (14-1077) U/l, and median treatment duration 18 (6-60) months. At months 12, 24, and 36, complete viral suppression rates were 41, 66, and 85% and HBeAg seroconversion rates were 4.8, 20, and 30%, respectively. No patients experienced adverse events or developed genotypic resistance to ETV.

CONCLUSION

In clinical settings, ETV is highly tolerable and potent at suppressing hepatitis B viremia; however, the rates of HBeAg seroconversion appear to be much lower than those reported, highlighting the importance of appropriate counseling and planning for long-term therapy.

OBJECTIVE

To evaluate long-term follow-up of a phase II trial of chemohormonal therapy in 62 men with prostate cancer biochemical relapse (BR).

METHODS

Treatment was 4 cycles of docetaxel (70 mg/m(2)) every 3 weeks and estramustine 280 mg three times a day (days 1-5) followed by 15 months of goserelin acetate/bicalutamide. The primary endpoint was the proportion with prostate-specific antigen (PSA) <0.1 with recovered testosterone 5 years after completion of therapy. Secondary endpoints included time to progression (TTP), time to reinitiate androgen deprivation therapy (ADT), the proportion with castration-resistant prostate cancer (CRPC), and overall survival (OS).

RESULTS

Median follow-up was 8.6 years (range 1.3-11.1 years). At 5 year follow-up, 7 patients (11%) had PSA <0.1 (5 undetectable); 8 (13%) had PSA >0.1 but without reinitiation of ADT (median PSA 0.37). Of the 15 (24%) men without reinitiation of ADT, and 14 have recovered testosterone to normal range. Median TTP for the complete cohort was 35.0 months (95% confidence interval [CI] 31.7-39.2). Baseline PSA <3.0 ng/dL, no prior ADT, and prostatectomy (vs radiation) were associated with longer TTP (P = .0001, P = .0055, and P = .0398, respectively). At the time of analysis, 42 men (68%) had restarted ADT, 23 men had CRPC (37%), and 11 (18%) had chemotherapy. Median time to reinitiation of ADT was 32.6 months (range 0-107.6 months). Median OS has not been reached; there were 15 deaths.

CONCLUSION

Chemotherapy plus ADT for BR resulted in durable (>5 years) complete responses (<0.1 ng/mL) in 7 men (11%). Twenty-four percent of men have not re-initiated ADT 5 years from completion of protocol therapy.