Hepatitis C Testing,Status and Treatment among Marginalized People Who Use Drugs in an Inner City Setting: An Observational Cohort Study

Background: Chronic hepatitis C virus (HCV) infection is common among people who inject drugs (PWID) and is associated with morbidity and premature death. Although HCV can be cured, treatment may be inaccessible. We studied HCV testing, status and treatment among marginalized people who use drugs in Ottawa, Canada, a setting with universal insurance coverage for physician services.

Methods: We analyzed data from the Participatory Research in Ottawa: Understanding Drugs study, a cross-sectional, peer-administered survey of people who use drugs from 2012 to 2013. We linked responses to population-based health administrative databases and used multivariable Poisson regression to identify factors independently associated with self-reported HCV testing, self-reported positive HCV status, and database-determined engagement in HCV treatment. Results: Among 663 participants, 562 (84.8%) reported testing for HCV and 258 (45.9%) reported HCV-positive status. In multivariable analysis, HCV-positive status was associated with female gender (RR 1.27; 95%CI 1.04 to 1.55), advancing age (RR 1.03/year; 95%CI 1.02 to 1.04), receiving disability payments (RR 1.42; 95%CI 1.06 to 1.91), injecting drugs (RR 5.11; 95%CI 2.64 to 9.91), ever injecting with a used needle (RR 1.30; 95%CI 1.12 to 1.52), and ever having taken methadone (RR 1.26; 95%CI 1.05 to 1.52). Of HCV positive participants, 196 (76%) were engaged in primary care but only 23 (8.9%) had received HCV therapy. Conclusions/Importance: Although HCV testing and positive status rates are high among PWID in our study, few have received HCV treatment. Innovative initiatives to increase access to HCV treatment for PWID are urgently needed.     

Do Optic Canal Dimensions Measured on CT Influence the Degree of Papilloedema and Visual Dysfunction in Idiopathic Intracranial Hypertension?

A recent study found that increased optic canal area on magnetic resonance imaging was associated with worse papilloedema in idiopathic intracranial hypertension (IIH). We repeated this study using more accurate computerized tomography derived measurements. Optic canal dimensions were measured from 42 IIH patients and 24 controls. These were compared with papilloedema grade. There was no correlation between any of the optic canal measurements and papilloedema grade and no significant difference in optic canal measurements between patients and controls. Our results cast doubt on the existing literature regarding the association between optic canal size and the degree of papilloedema in IIH.

CT delineates bony anatomy more accurately than MRI and our CT-derived optic canal measurements cast doubt on the existing literature regarding the association between optic canal size and the degree of Papilloedema in IIH.     

Mental health disorder,pain, and pain treatment among long-term care residents: Evidence from the Minimum Data Set 3.0

Objective: This study evaluated: (a) associations between long-term care residents’ mental health disorder diagnoses and their pain self-reports and pain treatments, and (b) the extent to which communication, cognitive, and physical functioning problems help explain disparities in the pain and pain treatments of long-term care residents with and without mental health disorders.

Method: Minimum Data Set 3.0 records of 8,300 residents of Department of Veterans Affairs Community Living Centers were used to determine statistically unadjusted and adjusted cross-sectional associations between residents' mental health diagnoses and their pain and pain treatments.

Results: Residents diagnosed with dementia and serious mental illness (SMI) were less likely, and those diagnosed with depressive disorder, post-traumatic stress disorder (PTSD), and substance use disorder (SUD) were more likely, to report recent, severe, and debilitating pain. Among residents affirming recent pain, those with dementia or SMI diagnoses were twice as likely to obtain no treatment for their pain and significantly less likely to receive as-needed pain medication and non-pharmacological pain treatments than were other residents. Those with either depressive disorder or PTSD were more likely, and those with SUD less likely, to obtain scheduled pain medication. In general, these associations remained even after statistically adjusting for residents' demographic characteristics, other mental health disorder diagnoses, and functioning.

Conclusion: Long-term care residents with mental health disorders experience disparities in pain and pain treatment that are not well-explained by their functioning deficits. They may benefit from more frequent, thorough pain assessments and from more varied and closely tailored pain treatment approaches.     

Macular buckle without vitrectomy for myopic macular schisis: a Canadian case series

Objective

To determine the effectiveness of a macular buckle procedure without vitrectomy for the treatment of symptomatic myopic macular schisis.

A randomized cross-over trial to define neurophysiological correlates of AV-101 N-methyl-d-aspartate receptor blockade in healthy veterans

The kynurenine pathway (KP) is a strategic metabolic system that combines regulation of neuronal excitability via glutamate receptor function and neuroinflammation via other KP metabolites. This pathway has great promise in treatment of depression and suicidality. The KP modulator AV-101 (4-chlorokynurenine, 4-Cl-KYN), an oral prodrug of 7-chlorokynurenic acid (7-Cl-KYNA), an N-methyl-d-aspartate receptor (NMDAR) glycine site antagonist, and of 4-chloro-3-hydroxyanthranilic acid (4-Cl-3-HAA), a suppressor of NMDAR agonist quinolinic acid (QUIN), is a promising potential antidepressant that targets glutamate functioning via the KP. However, a recent placebo-controlled clinical trial of AV-101 in depression found negative results. This raises the question of whether AV-101 can penetrate the brain and engage the NMDAR and KP effectively. To address this problem, ten healthy US military veterans (mean age = 32.6 years ± 6.11; 1 female) completed a phase-1 randomized, double-blind, placebo-controlled, crossover study to examine dose-related effects of AV-101 (720 and 1440 mg) on NMDAR engagement measured by γ-frequency band auditory steady-state response (40 Hz ASSR) and resting EEG. Linear mixed models revealed that 1440 mg AV-101, but not 720 mg, increased 40 Hz ASSR and 40 Hz ASSR γ-inter-trial phase coherence relative to placebo. AV-101 also increased 4-Cl-KYN, 7-Cl-KYNA, 4-Cl-3-HAA, 3-HAA, and KYNA in a dose-dependent manner, without affecting KYN and QUIN. AV-101 was safe and well tolerated. These results corroborate brain target engagement of 1440 mg AV-101 in humans, consistent with blockade of interneuronal NMDAR blockade. Future studies should test higher doses of AV-101 in depression. Suicidal behavior, which has been associated with high QUIN and low KYNA, is also a potential target for AV-101.Subject terms: Biomarkers, Neurophysiology, Neuroscience     

Investigation of Solid Dosage Form Components Interaction Using Orthogonal Techniques- Discovery of New Forms of Sodium Stearyl Fumarate

Physical or chemical interactions between drug product (DP) components can occur during manufacturing and/or upon storage; and may alter DP shelf life and performance. In this work a new Powder X-ray Diffraction (PXRD) peak was observed in DP under accelerated storage conditions. Due to the complex drug product matrix (including API, polymer, fillers, super disintegrant and lubricant), it was challenging to pinpoint the component(s) responsible for the new peak. In addition to PXRD, other orthogonal techniques including Differential Scanning Calorimetry (DSC), thermogravimetric analysis (TGA), dynamic vapor sorption (DVS), Solid State Nuclear Magnetic Resonance (SSNMR) and Infrared (IR) spectroscopy were employed in this investigation to understand the root cause mechanistically. Specifically, multi nuclei SSNMR (¹H, ²³Na, ¹³C) was instrumental in delineating the components of the matrix. We identified the root cause to be an acid base reaction occurring in the DP, whereby sodium ion in sodium stearyl fumarate (SSF) is replaced by proton leading to SSF form conversion. We also identified commercially available SSF to be a hydrate that can dehydrate to an anhydrous form upon heating. In general, the same techniques can be used to investigate interactions of any multi component solid dosage forms.     

Smoking cessation during alcohol treatment: a randomized trial of combination nicotine patch plus nicotine gum

Aims   The primary aim was to compare the efficacy of smoking cessation treatment using a combination of active nicotine patch plus active nicotine gum versus therapy consisting of active nicotine patch plus placebo gum in a sample of alcohol-dependent tobacco smokers in an early phase of out-patient alcohol treatment. A secondary aim was to determine whether or not there were any carry-over effects of combination nicotine replacement on drinking outcomes.
Design   Small-scale randomized double-blind placebo-controlled clinical trial with 1-year smoking and drinking outcome assessment.
Setting   Two out-patient substance abuse clinics provided a treatment platform of behavioral alcohol and smoking treatment delivered in 3 months of weekly sessions followed by three monthly booster sessions.
Participants   Participants were 96 men and women with a diagnosis of alcohol abuse or dependence and smoking 15 or more cigarettes per day.
Intervention   All participants received open-label transdermal nicotine patches and were randomized to receive either 2 mg nicotine gum or placebo gum under double-blind conditions.
Findings   Analysis of 1-year follow-up data revealed that patients receiving nicotine patch plus active gum had better smoking outcomes than those receiving patch plus placebo gum on measures of time to smoking relapse and prolonged abstinence at 12 months. Alcohol outcomes were not significantly different across medication conditions.
Conclusions   Results of this study were consistent with results of larger trials of smokers without alcohol problems, showing that combination therapy (nicotine patch plus gum) is more effective than monotherapy (nicotine patch) for smoking cessation.