Recanalization and outcomes after cerebral venous thrombosis: a systematic review and meta-analysis.

Background: Recanalization in cerebral venous thrombosis (CVT) can begin as early as 1 week after initiating therapeutic anticoagulation. The clinical significance of recanalization remains uncertain. Objectives: We aimed to investigate the association between recanalization and functional outcomes and explored predictors of recanalization. Methods: A systematic literature search was conducted (EMBASE, MEDLINE, Cochrane library) to identify: (1) patients with CVT aged ≥18 years treated with anticoagulation only; (2) case series, cohort, or randomized controlled trial studies; and (3) reported recanalization rates and functional outcomes using either a modified Rankin Scale (mRS) or sequelae of CVT at last follow-up. Meta-analysis was performed using pooled odds ratios (ORs) with exploration of sex and age effects using meta-regression. Results: Twenty-three studies were eligible with 1418 individual patients in total. Timing of reimaging and clinical reassessment was variable. Absence of recanalization was associated with increased odds of an unfavorable functional outcome (mRS 2-6 versus 0-1; OR, 3.66; 95% CI, 1.73-7.74; p = 0.001), CVT recurrence (OR, 8.81; 95% CI, 1.63-47.7; p = 0.01), and chronic headache (OR, 2.78; 95% CI, 1.16-6.70; p = 0.02). On meta-regression, the relationship between recanalization and mRS differed by the proportion of female patients, where lower proportions of women were associated with higher likelihood of a worse outcome, but not by mean participant age. There was no incremental benefit of full compared with partial recanalization with respect to favorable mRS or recurrence, but odds of chronic headache were higher with partial versus full recanalization (OR, 3.80; 95% CI, 1.43-10.11; p = 0.008). Epilepsy and visual sequelae were not associated with recanalization. Conclusions: Absence of recanalization was associated with worse functional outcomes, CVT recurrence, and headache, but outcomes were modified by sex. The degree of recanalization was significant in relation to headache outcomes, where partial compared with complete recanalization resulted in a greater likelihood of residual headache. Prospective studies with common timing of repeat clinical-neuroimaging assessments will help to better ascertain the relationship and directionality between the degree of recanalization and outcomes.

Accurate classification of carotid endarterectomy indication using physician claims and hospital discharge data.

BACKGROUND AND PURPOSE: Studies of carotid endarterectomy (CEA) require stratification by symptomatic vs asymptomatic status because of marked differences in benefits and harms. In administrative datasets, this classification has been done using hospital discharge diagnosis codes of uncertain accuracy. This study aims to develop and evaluate algorithms for classifying symptomatic status using hospital discharge and physician claims data. METHODS: A single center's administrative database was used to assemble a retrospective cohort of participants with CEA. Symptomatic status was ascertained by chart review prior to linkage with physician claims and hospital discharge data. Accuracy of rule-based classification by discharge diagnosis codes was measured by sensitivity and specificity. Elastic net logistic regression and random forest models combining physician claims and discharge data were generated from the training set and assessed in a test set of final year participants. Models were compared to rule-based classification using sensitivity at fixed specificity. RESULTS: We identified 971 participants undergoing CEA at the Vancouver General Hospital (Vancouver, Canada) between January 1, 2008 and December 31, 2016. Of these, 729 met inclusion/exclusion criteria (n = 615 training, n = 114 test). Classification of symptomatic status using hospital discharge diagnosis codes was 32.8% (95% CI 29-37%) sensitive and 98.6% specific (96-100%). At matched 98.6% specificity, models that incorporated physician claims data were significantly more sensitive: elastic net 69.4% (59-82%) and random forest 78.8% (69-88%). CONCLUSION: Discharge diagnoses were specific but insensitive for the classification of CEA symptomatic status. Elastic net and random forest machine learning algorithms that included physician claims data were sensitive and specific, and are likely an improvement over current state of classification by discharge diagnosis alone.

Updates in Cerebral Venous Thrombosis.

PURPOSE OF REVIEW: Cerebral venous thrombosis (CVT) is a rare cause of stroke that most commonly affects younger women. Here, we review new literature relevant to the management and prognosis of individuals with CVT and ongoing areas of uncertainty. RECENT FINDINGS: Direct-acting oral anticoagulants (DOACs) are being increasingly integrated into routine care but are not yet recommended by guidelines. Recent randomized clinical trials and available case series offer reassuring safety data. Routine use of endovascular therapy is not associated with improved outcomes. The relationship between recanalization and prognosis is uncertain. The evidence base for management of CVT continues to improve. Ongoing areas of uncertainty include duration of therapy and whether certain subgroups of patients may benefit from neurointervention or personalized approaches to antithrombotic strategy. The state of knowledge will continue to benefit from large collaborative international efforts, and integration of patient partnerships to identify research priorities.

Assessment of Prorated Scoring of an Abbreviated Protocol for the National Institutes of Health Toolbox Cognition Battery.

OBJECTIVE: To evaluate an abbreviated NIH Toolbox Cognition Battery (NIHTB-CB) protocol that can be administered remotely without any in-person assessments, and explore the agreement between prorated scores from the abbreviated protocol and standard scores from the full protocol. METHODS: Participant-level age-corrected NIHTB-CB data were extracted from six studies in individuals with a history of stroke, mild traumatic brain injury (mTBI), treatment-resistant psychosis, and healthy controls, with testing administered under standard conditions. Prorated fluid and total cognition scores were estimated using regression equations that excluded the three fluid cognition NIHTB-CB instruments which cannot be administered remotely. Paired t tests and intraclass correlations (ICCs) were used to compare the standard and prorated scores. RESULTS: Data were available for 245 participants. For fluid cognition, overall prorated scores were higher than standard scores (mean difference = +4.5, SD = 14.3; p < 0.001; ICC = 0.86). For total cognition, overall prorated scores were higher than standard scores (mean difference = +2.7, SD = 8.3; p < 0.001; ICC = 0.88). These differences were significant in the stroke and mTBI groups, but not in the healthy control or psychosis groups. CONCLUSIONS: Prorated scores from an abbreviated NIHTB-CB protocol are not a valid replacement for the scores from the standard protocol. Alternative approaches to administering the full protocol, or corrections to scoring of the abbreviated protocol, require further study and validation.

Glecaprevir/pibrentasvir+sofosbuvir: an optimal retreatment strategy in the setting of HCV NS5A resistance.

Some individuals do not achieve a cure of their hepatitis C virus (HCV) infection due to non-adherence or resistance associated substitutions. Salvage options that are optimised for resistance profiles are essential. We report a 56-year-old Caucasian man with fatigue, depression and confusion in the setting of untreated HCV genotype 3a infection. He received ruzasvir and uprifosbuvir for 12 weeks within a clinical trial. The patient relapsed 4 weeks after the end of treatment and at this time resistance testing showed multiple resistances including a NS5A Y93H mutation. Given that this mutation confers resistance to first line salvage options, sofosbuvir and glecaprevir/pibrentasvir was used for 12 weeks and the patient was cured of HCV infection 12 weeks after the end of treatment. This shows that sofosbuvir and glecaprevir/pibrentasvir is a viable, effective option for second line/salvage therapy of HCV infection in the setting of resistance to NS5A inhibitors with the Y93H mutation.

Low rate of reinfection among a cohort of people who use drugs successfully treated for hepatitis C virus infection in Vancouver, Canada.

INTRODUCTION: Concerns about reinfection may be limiting HCV treatment uptake among people who use drugs (PWUD), with rates of 17.1/100 person-years in some cohorts. The aim of this study was to evaluate reinfection following successful treatment for hepatitis C virus infection in a cohort of people who inject drugs in Vancouver, Canada. METHODS: We identified a cohort of HCV-infected PWUD treated at our centre. Following cure, patients were maintained in long-term follow-up in a multidisciplinary program to address their medical, psychological, social, and addiction-related needs. HCV RNA measurements were repeated every 6 months, and ongoing drug use was documented. The primary outcome of this analysis was the occurrence of reinfection. RESULTS: 243 recent PWUD (use within 6 months of treatment initiation) have achieved SVR and maintained in long-term follow-up. Ongoing drug use post-treatment was documented in 195 individuals. Key characteristics: mean age 53 years, 25% female, 78% treatment naïve, 17% cirrhotic. Reinfection occurred in 4 cases, all in patients with ongoing drug use. This incidence was 1.05/100 [95% 0.8-5.2] person years based on 379 person-years of follow-up in individuals currently using drugs. CONCLUSION: Approaches including long-term maintenance in multidisciplinary care may optimize long-term outcomes of HCV treatment in PWUD.

Real-world Efficacy of Direct-Acting Antiviral Therapy for HCV Infection Affecting People Who Inject Drugs Delivered in a Multidisciplinary Setting.

BACKGROUND: Many clinicians and insurance providers are reluctant to embrace recent guidelines identifying people who inject drugs (PWID) as a priority population to receive hepatitis C virus (HCV) treatment. The aim of this study was to evaluate the efficacy of direct-acting antiviral (DAA) HCV therapy in a real-world population comprised predominantly of PWID. METHODS: A retrospective analysis was performed on all HCV-infected patients who were treated at the Vancouver Infectious Diseases Centre between March 2014 and December 2017. All subjects were enrolled in a multidisciplinary model of care, addressing medical, psychological, social, and addiction-related needs. The primary outcome was achievement of sustained virologic response (undetectable HCV RNA) 12 or more weeks after completion of HCV therapy (SVR-12). RESULTS: Overall, 291 individuals were enrolled and received interferon-free DAA HCV therapy. The mean age was 54 years, 88% were PWID, and 20% were HCV treatment experienced. At data lock, 62 individuals were still on treatment and 229 were eligible for evaluation of SVR by intent-to-treat (ITT) analysis. Overall, 207 individuals achieved SVR (90%), with 13 losses to follow-up, 7 relapses, and 2 premature treatment discontinuations. ITT SVR analysis show that active PWID and treatment-naïve patients were less likely to achieve SVR (P = .0185 and .0317, respectively). Modified ITT analysis of active PWID showed no difference in achieving SVR (P = .1157) compared with non-PWID. CONCLUSION: Within a multidisciplinary model of care, the treatment of HCV-infected PWID with all-oral DAA regimens is safe and highly effective. These data justify targeted efforts to enhance access to HCV treatment in this vulnerable and marginalized population.

Diagnosis and treatment of hepatitis C virus infection: a tool for engagement with people who inject drugs in Vancouver's Downtown Eastside.

Background: Vancouver's Downtown Eastside (DTES) faces the interrelated challenges of poverty, homelessness, mental health, addiction, and medical issues such as hepatitis C virus (HCV). This study evaluates a new model of engagement with people who inject drugs (PWID) in the DTES. Methods: Our centre has developed the community pop-up clinic (CPC) to engage vulnerable populations such as PWID. Rapid HCV testing is offered using the OraQuick saliva assay. If a test is positive, immediate medical consultation and an incentivized clinic appointment are offered. At this appointment, an HCV treatment plan is developed, along with a plan for engagement in multidisciplinary care. Results: In 12 months, 1,283 OraQuick tests were performed at 44 CPCs; 21% of individuals were found to be positive for HCV (68% of whom were PWID). Of individuals positive for HCV antibodies who consulted with the on-site doctor, 50% engaged in care in our clinic-61% of whom have initiated interferon-free directly acting antiviral (DAA) HCV therapy with 100% cured of HCV (per protocol). Individuals who did not engage in care were significantly more likely to be homeless (P < .0001). Conclusion: CPCs paired with a multidisciplinary model of care address the needs of vulnerable populations such as PWID, particularly in the management of HCV with interferon-free DAA therapies.

Repeated spontaneous clearance of hepatitis C virus infection in the setting of long-term non-progression of HIV infection.

Hepatitis C Virus (HCV) and human immunodeficiency virus (HIV) are global pandemics that affect 170 million and 35 million individuals, respectively. Up to 45% of individuals infected with HCV clear their infections spontaneously - correlating to factors like aboriginal descent and some host specific immune factors. HIV, however, establishes true latency in infected cells and cannot be cured. In the setting of longterm non-progressors (LTNPs) of HIV, a state of immune preservation and low circulating viral load is established. Regarding HIV/HCV co-infection, little is known about the relationship between spontaneous clearance of HCV infection and long-term control of HIV infection without medical intervention. We describe a case of a HIV-infected female defined as a LTNP in whom spontaneous clearance of HCV was documented on multiple occasions. Similar cases should be documented and identified in an effort to develop novel hypotheses about the natural control of these infections and inform research on immune-based interventions to control them.