Housing Stability and Hepatitis C Infection for Young Adults Who Inject Drugs: Examining the Relationship of Consistent and Intermittent Housing Status on HCV Infection Risk.

Housing status affects drug using behaviors, but less is known about the relationship between housing patterns and hepatitis C virus (HCV) infection. HCV-negative young people who inject drugs (PWID) were enrolled into a prospective cohort (2003-2019) with quarterly study visits. We used Cox regression to estimate the independent association of recent housing status (housed vs. unhoused, housing stability, and housing trajectory) on HCV incidence. Among 712 participants, 245 incident HCV infections occurred over 963.8 person-years (py) (cumulative incidence 24.4/100 py). An inverse relationship between time housed and HCV incidence was observed (always unhoused 45.0/100 py, 95% confidence interval (CI) 37.1, 54.5; variably housed 18.0/100 py, 95% CI 15.0, 21.3; and always housed 7.0/100 py, 95% CI 3.0, 17.3). In Cox regression models controlling for confounders, those unhoused versus housed at baseline had a 1.9-fold increased infection risk (95% CI 1.4, 2.6). Those always unhoused versus always housed had a 1.5 times greater risk of HCV (95% CI 1.0, 2.3), and those spending a portion of time in stable housing a lower risk (adjusted relative hazard 0.05, 95% CI 0.3, 0.9) with a similar trend for those being housed for less time. Young adult PWID experiencing both recent and chronic states of being unhoused are at elevated risk for HCV infection. Importantly for this group of PWID, our findings indicate that some frequency of residential housing significantly reduces HCV infection risk.

External Validation of the STONE Score, a Clinical Prediction Rule for Ureteral Stone: An Observational Multi-institutional Study.

STUDY OBJECTIVE: The STONE score is a clinical decision rule that classifies patients with suspected nephrolithiasis into low-, moderate-, and high-score groups, with corresponding probabilities of ureteral stone. We evaluate the STONE score in a multi-institutional cohort compared with physician gestalt and hypothesize that it has a sufficiently high specificity to allow clinicians to defer computed tomography (CT) scan in patients with suspected nephrolithiasis. METHODS: We assessed the STONE score with data from a randomized trial for participants with suspected nephrolithiasis who enrolled at 9 emergency departments between October 2011 and February 2013. In accordance with STONE predictors, we categorized participants into low-, moderate-, or high-score groups. We determined the performance of the STONE score and physician gestalt for ureteral stone. RESULTS: Eight hundred forty-five participants were included for analysis; 331 (39%) had a ureteral stone. The global performance of the STONE score was superior to physician gestalt (area under the receiver operating characteristic curve=0.78 [95% confidence interval {CI} 0.74 to 0.81] versus 0.68 [95% CI 0.64 to 0.71]). The prevalence of ureteral stone on CT scan ranged from 14% (95% CI 9% to 19%) to 73% (95% CI 67% to 78%) in the low-, moderate-, and high-score groups. The sensitivity and specificity of a high score were 53% (95% CI 48% to 59%) and 87% (95% CI 84% to 90%), respectively. CONCLUSION: The STONE score can successfully aggregate patients into low-, medium-, and high-risk groups and predicts ureteral stone with a higher specificity than physician gestalt. However, in its present form, the STONE score lacks sufficient accuracy to allow clinicians to defer CT scan for suspected ureteral stone.

Phase II study of high-dose [131I]metaiodobenzylguanidine therapy for patients with metastatic pheochromocytoma and paraganglioma.

PURPOSE: To evaluate the safety and efficacy of high-dose [(131)I]metaiodobenzylguanidine ([(131)I]MIBG) in the treatment of malignant pheochromocytoma (PHEO) and paraganglioma (PGL). METHODS: Fifty patients with metastatic PHEO or PGL, age 10 to 64 years, were treated with [(131)I]MIBG doses ranging from 492 to 1,160 mCi (median, 12 mCi/kg). Cumulative [(131)I]MIBG administered ranged from 492 to 3,191 mCi. Autologous hematopoietic stem cells were collected and cryopreserved before treatment with [(131)I]MIBG greater than 12 mCi/kg or with a total dose greater than 500 mCi. Sixty-nine [(131)I]MIBG infusions were given, which included infusions to 35 patients treated once and infusions to 15 patients who received two or three treatments. Response was evaluated by [(123)I]MIBG scans, computed tomography/magnetic resonance imaging, urinary catecholamines/metanephrines, and chromogranin A. RESULTS: The overall complete response (CR) plus partial response (PR) rate in 49 evaluable patients was 22%. Additionally, 35% of patients achieved a CR or PR in at least one measure of response without progressive disease, and 8% of patients maintained stable disease for greater than 12 months. Thirty-five percent of patients experienced progressive disease within 1 year after therapy. The estimated 5-year overall survival rate was 64%. Toxicities included grades 3 to 4 neutropenia (87%) and thrombocytopenia (83%). Grades 3 to 4 nonhematologic toxicity included acute respiratory distress syndrome (n = 2), bronchiolitis obliterans organizing pneumonia (n = 2), pulmonary embolism (n = 1), fever with neutropenia (n = 7), acute hypertension (n = 10), infection (n = 2), myelodysplastic syndrome (n = 2), and hypogonadism (n = 4). CONCLUSION: Although serious toxicity may occur, the survival and response rates achieved with high-dose [(131)I]MIBG suggest its utility in the management of selected patients with metastatic PHEO and PGL.

Analyzing Direct Effects in Randomized Trials with Secondary Interventions: An Application to HIV Prevention Trials.

The Methods for Improving Reproductive Health in Africa (MIRA) trial is a recently completed randomized trial that investigated the effect of diaphragm and lubricant gel use in reducing HIV infection among susceptible women. 5,045 women were randomly assigned to either the active treatment arm or not. Additionally, all subjects in both arms received intensive condom counselling and provision, the "gold standard" HIV prevention barrier method. There was much lower reported condom use in the intervention arm than in the control arm, making it difficult to answer important public health questions based solely on the intention-to-treat analysis. We adapt an analysis technique from causal inference to estimate the "direct effects" of assignment to the diaphragm arm, adjusting for condom use in an appropriate sense. Issues raised in the MIRA trial apply to other trials of HIV prevention methods, some of which are currently being conducted or designed.

Interleukin-2 therapy restores CD8 cell non-cytotoxic anti-HIV responses in primary infection subjects receiving HAART.

OBJECTIVE: To determine the effect of interleukin-2 (IL-2) therapy on immunologic and virologic responses in subjects with acute or recent HIV infection already receiving highly active antiretroviral therapy (HAART). METHODS: The effect of IL-2 therapy on immunologic and virologic responses was studied in 21 acutely infected individuals who had been receiving HAART for 48 weeks following acute or recent HIV infection. Nine subjects receiving no therapy served as controls. Viral loads, as well as CD4 and CD8 cell counts were monitored and the CD8 cell non-cytotoxic anti-HIV response (CNAR) was measured. RESULTS: IL-2 therapy led to significant increases in CD4 cell numbers (P = 0.005) that were maintained for 6 months after discontinuation of the IL-2 treatment. No effect of IL-2 was observed on viral loads or the CD8 cell numbers as compared to subjects receiving HAART alone. CNAR activity was restored among subjects receiving HAART and IL-2 whereas CNAR declined among those receiving HAART alone and in untreated infected subjects. The percentage of HAART subjects with CD8 cells showing at least 50% suppression of HIV replication increased significantly following IL-2 therapy (P = 0.02) and persisted for 6 months. CONCLUSIONS: In primary HIV infection administering IL-2 concomitant with HAART following 1 year of treatment with HAART gives a significant increase in CD4 cells and a previously unrecognized beneficial effect on the CD8 cell non-cytotoxic anti-HIV response.

Risk of HIV infection attributable to oral sex among men who have sex with men and in the population of men who have sex with men.

We examined HIV infection and estimated the population-attributable risk percentage (PAR%) for HIV associated fellatio among men who have sex with other men (MSM). Among 239 MSM who practised exclusively fellatio in the past 6 months, 50% had three partners, 98% unprotected; and 28% had an HIV-positive partner; no HIV was detected. PAR%, based on the number of fellatio partners, ranges from 0.10% for one partner to 0.31% for three partners. The risk of HIV attributable to fellatio is extremely low.