Addressing ADL ability in people with poststroke cognitive impairments: A Danish survey of clinical practice.

BACKGROUND: In Denmark, stroke represents a leading disability cause. While people with difficulties in performing activities of daily living (ADL) due to poststroke cognitive impairments are often referred to occupational therapy, limited knowledge is available on the nature of these services. AIM/OBJECTIVE: To explore how Danish occupational therapists describe their practice when addressing decreased ADL ability in people with poststroke cognitive impairments in hospital and municipality settings. MATERIAL AND METHODS: National, cross-sectorial, web-based public survey. RESULTS: 244 occupational therapists accessed the survey; 172 were included in the analysis. Most respondents could indicate the theory guiding their reasoning; half used standardised assessments. Regarding intervention, restorative and acquisitional models were preferred; specific strategies were identified. Intensity: 30-45 min 3-4 times/week in hospitals; 30-60 min 1-2 times/week in municipalities. CONCLUSIONS: Therapists report to be guided by theory in their reasoning. Standardised assessments are used to a higher extend than previously reported. Still, the results invite critical reflections on correct use of assessment instruments, content and intensity of interventions, and how therapists keep themselves updated. SIGNIFICANCE: The results document the need for practice improvements and may inform the definition of standard care in future trials.

Comprehensive Venous Outflow Predicts Functional Outcomes in Patients with Acute Ischemic Stroke Treated by Thrombectomy.

BACKGROUND AND PURPOSE: Cortical venous outflow has emerged as a robust measure of collateral blood flow in acute ischemic stroke. The addition of deep venous drainage to this assessment may provide valuable information to further guide the treatment of these patients. MATERIALS AND METHODS: We performed a multicenter retrospective cohort study of patients with acute ischemic stroke treated by thrombectomy between January 2013 and January 2021. The internal cerebral veins were scored on a scale of 0-2. This metric was combined with existing cortical vein opacification scores to create a comprehensive venous outflow score from 0 to 8 and stratify patients as having favorable-versus-unfavorable comprehensive venous outflow. Outcome analyses were primarily conducted using the Mann-Whitney U and χ2 tests. RESULTS: Six hundred seventy-eight patients met the inclusion criteria. Three hundred fifteen were stratified as having favorable comprehensive venous outflow (mean age, 73 years; range, 62-81 years; 170 men), and 363, as having unfavorable comprehensive venous outflow (mean age, 77 years; range, 67-85 years; 154 men). There were significantly higher rates of functional independence (mRS 0-2; 194/296 versus 37/352, 66% versus 11%, P < .001) and excellent reperfusion (TICI 2c/3; 166/313 versus 142/358, 53% versus 40%, P < .001) in patients with favorable comprehensive venous outflow. There was a significant increase in the association of mRS with the comprehensive venous outflow score compared with the cortical vein opacification score (-0.74 versus -0.67, P = .006). CONCLUSIONS: A favorable comprehensive venous profile is strongly associated with functional independence and excellent postthrombectomy reperfusion. Future studies should focus on patients with venous outflow status that is discrepant with the eventual outcome.

Validation of a suite of ERP and QEEG biomarkers in a pre-competitive, industry-led study in subjects with schizophrenia and healthy volunteers.

OBJECTIVE: Complexity and lack of standardization have mostly limited the use of event-related potentials (ERPs) and quantitative EEG (QEEG) biomarkers in drug development to small early phase trials. We present results from a clinical study on healthy volunteers (HV) and patients with schizophrenia (SZ) that assessed test-retest, group differences, variance, and correlation with functional assessments for ERP and QEEG measures collected at clinical and commercial trial sites with standardized instrumentation and methods, and analyzed through an automated data analysis pipeline. METHODS: 81 HV and 80 SZ were tested at one of four study sites. Subjects were administered two ERP/EEG testing sessions on separate visits. Sessions included a mismatch negativity paradigm, a 40 Hz auditory steady-state response paradigm, an eyes-closed resting state EEG, and an active auditory oddball paradigm. SZ subjects were also tested on the Brief Assessment of Cognition (BAC), Positive and Negative Syndrome Scale (PANSS), and Virtual Reality Functional Capacity Assessment Tool (VRFCAT). RESULTS: Standardized ERP/EEG instrumentation and methods ensured few test failures. The automated data analysis pipeline allowed for near real-time analysis with no human intervention. Test-retest reliability was fair-to-excellent for most of the outcome measures. SZ subjects showed significant deficits in ERP and QEEG measures consistent with published academic literature. A subset of ERP and QEEG measures correlated with functional assessments administered to the SZ subjects. CONCLUSIONS: With standardized instrumentation and methods, complex ERP/EEG testing sessions can be reliably performed at clinical and commercial trial sites to produce high-quality data in near real-time.

Application of 89Zr-DFO*-immuno-PET to assess improved target engagement of a bispecific anti-amyloid-ß monoclonal antibody.

PURPOSE: The recent conditional FDA approval of Aducanumab (Adu) for treating Alzheimer's disease (AD) and the continued discussions around that decision have increased interest in immunotherapy for AD and other brain diseases. Reliable techniques for brain imaging of antibodies may guide decision-making in the future but needs further development. In this study, we used 89Zr-immuno-PET to evaluate the targeting and distribution of a bispecific brain-shuttle IgG based on Adu with transferrin receptor protein-1 (TfR1) shuttling mechanism, mAbAdu-scFab8D3, designated Adu-8D3, as a candidate theranostic for AD. We also validated the 89Zr-immuno-PET platform as an enabling technology for developing new antibody-based theranostics for brain disorders. METHODS: Adu, Adu-8D3, and the non-binding control construct B12-8D3 were modified with DFO*-NCS and radiolabeled with 89Zr. APP/PS1 mice were injected with 89Zr-labeled mAbs and imaged on days 3 and 7 by positron emission tomography (PET). Ex vivo biodistribution was performed on day 7, and ex vivo autoradiography and immunofluorescence staining were done on brain tissue to validate the PET imaging results and target engagement with amyloid-ß plaques. Additionally, [89Zr]Zr-DFO*-Adu-8D3 was evaluated in 3, 7, and 10-month-old APP/PS1 mice to test its potential in early stage disease. RESULTS: A 7-fold higher brain uptake was observed for [89Zr]Zr-DFO*-Adu-8D3 compared to [89Zr]Zr-DFO*-Adu and a 2.7-fold higher uptake compared to [89Zr]Zr-DFO*-B12-8D3 on day 7. Autoradiography and immunofluorescence of [89Zr]Zr-DFO*-Adu-8D3 showed co-localization with amyloid plaques, which was not the case with the Adu and B12-8D3 conjugates. [89Zr]Zr-DFO*-Adu-8D3 was able to detect low plaque load in 3-month-old APP/PS1 mice. CONCLUSION: 89Zr-DFO*-immuno-PET revealed high and specific uptake of the bispecific Adu-8D3 in the brain and can be used for the early detection of Aß plaque pathology. Here, we demonstrate that 89Zr-DFO*-immuno-PET can be used to visualize and quantify brain uptake of mAbs and contribute to the evaluation of biological therapeutics for brain diseases.

The effect of ketamine and D-cycloserine on the high frequency resting EEG spectrum in humans.

RATIONALE: Preclinical studies indicate that high-frequency oscillations, above 100 Hz (HFO:100-170 Hz), are a potential translatable biomarker for pharmacological studies, with the rapid acting antidepressant ketamine increasing both gamma (40-100 Hz) and HFO. OBJECTIVES: To assess the effect of the uncompetitive NMDA antagonist ketamine, and of D-cycloserine (DCS), which acts at the glycine site on NMDA receptors on HFO in humans. METHODS: We carried out a partially double-blind, 4-way crossover study in 24 healthy male volunteers. Each participant received an oral tablet and an intravenous infusion on each of four study days. The oral treatment was either DCS (250 mg or 1000 mg) or placebo. The infusion contained 0.5 mg/kg ketamine or saline placebo. The four study conditions were therefore placebo-placebo, 250 mg DCS-placebo, 1000 mg DCS-placebo, or placebo-ketamine. RESULTS: Compared with placebo, frontal midline HFO magnitude was increased by ketamine (p = 0.00014) and 1000 mg DCS (p = 0.013). Frontal gamma magnitude was also increased by both these treatments. However, at a midline parietal location, only HFO were increased by DCS, and not gamma, whilst ketamine increased both gamma and HFO at this location. Ketamine induced psychomimetic effects, as measured by the PSI scale, whereas DCS did not increase the total PSI score. The perceptual distortion subscale scores correlated with the posterior low gamma to frontal high beta ratio. CONCLUSIONS: Our results suggest that, at high doses, a partial NMDA agonist (DCS) has similar effects on fast neural oscillations as an NMDA antagonist (ketamine). As HFO were induced without psychomimetic effects, they may prove a useful drug development target.

Healthcare cost variation in patients with heart failure: a nationwide study.

OBJECTIVE: Heart failure (HF) imposes a major economic burden; however, the individual management for patients varies, potentially leading to large cost heterogeneity. The aim of this study was to investigate the spectrum of health cost by patients with HF and factors associated with high direct health cost. STUDY DESIGN: This was a nationwide, retrospective longitudinal study. METHODS: Using Danish nationwide registries from 2012 to 2015, we identified all patients aged >18 years with a first-time diagnosis of HF. Total health costs were investigated using two perspectives-at index and during 3 years of follow-up. Patients were investigated by decile cost groups. A multivariable logistic regression was used to identify variables associated with being in the highest cost decile compared with the rest (90%). RESULTS: A total of 11,170 patients with HF were included, and those in the highest cost decile (n = 1117, 10%) were younger (69 vs. 75 years), fewer were females (34% vs. 43%), and more were inpatients (83% vs. 70%) compared with the rest of the patients with HF (n = 10,053, 90%). Patients in the highest cost decile (10%) incurred a 30 times higher cost with a mean total health cost in index year of €86,607 compared with €2893 for patients in lowest cost decile (10%). The results were similar for 3 years aggregated (€139,473 vs. €4086), corresponding to a 34 times higher cost. CONCLUSION: In patients with HF, a large total health cost heterogeneity exists with younger age, inpatient admittance, male sex, and comorbidities being associated with a higher likelihood of belonging to the highest cost group.

Tissue at Risk and Ischemic Core Estimation Using Deep Learning in Acute Stroke.

BACKGROUND AND PURPOSE: In acute stroke patients with large vessel occlusions, it would be helpful to be able to predict the difference in the size and location of the final infarct based on the outcome of reperfusion therapy. Our aim was to demonstrate the value of deep learning-based tissue at risk and ischemic core estimation. We trained deep learning models using a baseline MR image in 3 multicenter trials. MATERIALS AND METHODS: Patients with acute ischemic stroke from 3 multicenter trials were identified and grouped into minimal (≤20%), partial (20%-80%), and major (≥80%) reperfusion status based on 4- to 24-hour follow-up MR imaging if available or into unknown status if not. Attention-gated convolutional neural networks were trained with admission imaging as input and the final infarct as ground truth. We explored 3 approaches: 1) separate: train 2 independent models with patients with minimal and major reperfusion; 2) pretraining: develop a single model using patients with partial and unknown reperfusion, then fine-tune it to create 2 separate models for minimal and major reperfusion; and 3) thresholding: use the current clinical method relying on apparent diffusion coefficient and time-to-maximum of the residue function maps. Models were evaluated using area under the curve, the Dice score coefficient, and lesion volume difference. RESULTS: Two hundred thirty-seven patients were included (minimal, major, partial, and unknown reperfusion: n = 52, 80, 57, and 48, respectively). The pretraining approach achieved the highest median Dice score coefficient (tissue at risk = 0.60, interquartile range, 0.43-0.70; core = 0.57, interquartile range, 0.30-0.69). This was higher than the separate approach (tissue at risk = 0.55; interquartile range, 0.41-0.69; P = .01; core = 0.49; interquartile range, 0.35-0.66; P = .04) or thresholding (tissue at risk = 0.56; interquartile range, 0.42-0.65; P = .008; core = 0.46; interquartile range, 0.16-0.54; P < .001). CONCLUSIONS: Deep learning models with fine-tuning lead to better performance for predicting tissue at risk and ischemic core, outperforming conventional thresholding methods.

High prevalence of comorbidities and use of concomitant medication in treated people living with HIV in Germany - results of the BESIDE study.

Due to demographic changes in people living with HIV (PLHIV), physicians are challenged with age-related comorbidities and their management. In the absence of comprehensive data collection, the burden of comorbidities and co-medication in addition to antiretroviral therapy (ART) remains unclear for the German real-world setting. BESIDE was an observational, cross-sectional study evaluating the prevalence of comorbidities and use of co-medication in treated PLHIV. Regional distribution of study centers (n = 20), consecutive patient recruitment, and age-stratified sampling in alignment with national epidemiologic data aimed to ensure a representative sample (n = 453). The overall prevalence of comorbidities was 91.2%; 31.6% of patients had ≥4 comorbidities. The most common diagnoses were vitamin D deficiency (29.1%), depressive episode (27.8%), arterial hypertension (16.3%), and hypercholesterolemia (10.8%). 83.7% of patients were on co-medication; 21.2% taking ≥4 medications. The most common medications or supplements were vitamins (31.6%), anti-inflammatory agents (16.1%), renin-angiotensin system agents (12.1%), acid suppressants (11.7%), lipid modifying agents (10.8%); 1.3% of patients were on co-medication that should not be co-administered with ART, 41.5% on co-medication with potential for drug-drug interactions. The prevalence of comorbidities and use of co-medication among treated PLHIV in Germany is consistently high and increases across age groups, illustrating the complexity of HIV care involving appropriate ART selection.

A versatile Johansson-type tender x-ray emission spectrometer.

We present a high energy resolution x-ray spectrometer for the tender x-ray regime (1.6-5.0 keV) that was designed and operated at Stanford Synchrotron Radiation Lightsource. The instrument is developed on a Rowland geometry (500 mm of radius) using cylindrically bent Johansson analyzers and a position sensitive detector. By placing the sample inside the Rowland circle, the spectrometer operates in an energy-dispersive mode with a subnatural line-width energy resolution (∼0.32 eV at 2400 eV), even when an extended incident x-ray beam is used across a wide range of diffraction angles (∼30° to 65°). The spectrometer is enclosed in a vacuum chamber, and a sample chamber with independent ambient conditions is introduced to enable a versatile and fast-access sample environment (e.g., solid/gas/liquid samples, in situ cells, and radioactive materials). The design, capabilities, and performance are presented and discussed.

Absence of colon as the predominant risk factor for liver fibrosis in adults requiring home parenteral nutrition.

BACKGROUND: Liver fibrosis is a well-known complication of long-term use of parenteral nutrition in patients with intestinal failure associated to the nutrient composition in parenteral nutrition. This study investigates the prevalence of significant liver fibrosis and identifies risk factors for liver fibrosis. METHODS: This was a retrospective study of 35 parenteral nutrition-dependent patients with intestinal failure and 54 patients with intestinal insufficiency and oral nutrition only with a valid liver stiffness measurement obtained with transient elastography from November 2016 to August 2018. Clinical and demographic parameters including age, fat mass index and fat-free mass index, intact colon or colectomy, and nutritional management were analyzed for their association with liver stiffness. RESULTS: A prevalence for liver fibrosis (liver stiffness >7.0 kPa) was established at 37.1% in parenteral nutrition-dependent patients and at 22.2% in patients on oral nutrition. Several factors were significantly and independently associated with liver fibrosis including lipids in home parenteral nutrition (OR 10.66, p = 0.010) and colectomies (OR 3.24, p = 0.036). CONCLUSION: More than a third of patients receiving home parenteral nutrition have liver fibrosis. Several risk factors were demonstrated such as the amount of lipids and performed colectomies despite current international guidelines for lipids are followed. Our findings emphasize suggest a new perspective to prevent significant hepatic complications: colectomies.

Synergistic effects of a cremophor EL drug delivery system and its U0126 cargo in an ex vivo model.

Neuroprotection has proven clinically unsuccessful in subarachnoid hemorrhage. We believe that this is because the major component in the early damage pathway, the vascular wall, has not been given the necessary focus. U0126 is a potent inhibitor of vascular phenotypical changes, exemplified by functional endothelin B (ETB) receptor upregulation. The current study aimed to determine the optimal dose of U0126 ex vivo and test the toxicology of this dose in vivo. To find the optimal dose and test a suitable in vivo delivery system, we applied an ex vivo model of blood flow cessation and investigated functional ETB receptor upregulation (using a specific agonist) as the primary endpoint. The secondary endpoint was depolarization-induced contractility assessed by 60 mM K+ stimuli. Furthermore, an in vivo toxicology study was performed on the optimal selected doses. U0126 (10 µM) had a strong effect on the prevention of functional ETB receptor contractility, combined with minimal effect on the depolarization-induced contractility. When cremophor EL was chosen for drug delivery, it had an inhibitory and additive effect (combined with U0126) on the ETB receptor contractility. Hence, 10 µM U0126 in 0.5% cremophor EL seems to be a dose that will be close to the maximal inhibition observed ex vivo on basilar arteries, without exhibiting side effects in the toxicology studies. U0126 and cremophor EL are well tolerated at doses that have effect on ETB receptor upregulation. Cremophor EL has an additional positive effect, preventing functional ETB receptor upregulation, making it suitable as a drug delivery system.

Assessment of range and quality of neck movement using a smartphone-based application.

This study had the objective of measuring the validity of using a smartphone-based application to measure range of motion (ROM) and quality of movement (QOM) of neck motion by comparing it with 3D-motion capture analysis. METHODS: Thirty healthy volunteers participated in this cross-sectional study. A helmet fitted with markers for motion capture analysis and a smartphone were fastened to the head of the participants. The smartphone recorded data using a beta version of Balancy (MEDEI, Denmark). Assessments of full active movement in transverse and sagittal planes were performed. Recordings were made simultaneously with the camera system and the smartphone. ROM and jerkiness were compared with a repeated measures ANOVA and a Pearson product moment was calculated to compare the outcomes from the different applications. Bland-Altman plots were generated to determine the levels of agreement. RESULTS: No difference was found between modalities when comparing measurements of jerkiness or ROM. An excellent Pearson product moment was found for the outcomes of the two modalities for ROM (Pearson's r: 0.83 - 0.96) and jerkiness (Pearson's r: 0.86 - 0.95). The Bland-Altman plot revealed a systemic offset where the phone consistently measured higher values for ROM and lower values for jerkiness. CONCLUSIONS: This study demonstrated that a smartphone-based application can be used to accurately measure ROM and jerkiness during neck movements. These results indicate the utility of using a smartphone-based application to assess neck movement in humans. The findings have implications for assessment of neck movement in research and clinical practice.

Reviewing research priorities in weed ecology, evolution and management: a horizon scan.

Weedy plants pose a major threat to food security, biodiversity, ecosystem services and consequently to human health and wellbeing. However, many currently used weed management approaches are increasingly unsustainable. To address this knowledge and practice gap, in June 2014, 35 weed and invasion ecologists, weed scientists, evolutionary biologists and social scientists convened a workshop to explore current and future perspectives and approaches in weed ecology and management. A horizon scanning exercise ranked a list of 124 pre-submitted questions to identify a priority list of 30 questions. These questions are discussed under seven themed headings that represent areas for renewed and emerging focus for the disciplines of weed research and practice. The themed areas considered the need for transdisciplinarity, increased adoption of integrated weed management and agroecological approaches, better understanding of weed evolution, climate change, weed invasiveness and finally, disciplinary challenges for weed science. Almost all the challenges identified rested on the need for continued efforts to diversify and integrate agroecological, socio-economic and technological approaches in weed management. These challenges are not newly conceived, though their continued prominence as research priorities highlights an ongoing intransigence that must be addressed through a more system-oriented and transdisciplinary research agenda that seeks an embedded integration of public and private research approaches. This horizon scanning exercise thus set out the building blocks needed for future weed management research and practice; however, the challenge ahead is to identify effective ways in which sufficient research and implementation efforts can be directed towards these needs.

Exploring the metabolic variation between domesticated and wild tetraploid wheat genotypes in response to corn leaf aphid infestation.

Infestation of Triticum (wheat) plants by their pest Rhopalosiphum maidis (corn leaf aphid) causes severe vegetative damage. Despite the agro-economic importance of wheat, the metabolic diversity of Triticum turgidum (tetraploid wheat) in response to aphid attack has not been sufficiently addressed. In this study, we compared the metabolic diversity of two tetraploid wheat genotypes, domesticated and wild emmer. The plants were grown in a control growth room and infested with aphids for 96 h. Our untargeted metabolic analysis performed on plants with and without aphids revealed massive differences between the two genotypes. The targeted metabolic analysis highlighted the differences in the biosynthesis of phytohormones. The aphid progeny was lower in the cultivated durum wheat than in the wild emmer wheat. Overall, these observations emphasize the potential of using the natural diversity of wheat species to better understand the metabolic responses to pest damage.

Intensive care doctors' preferences for arterial oxygen tension levels in mechanically ventilated patients.

BACKGROUND: Oxygen is liberally administered in intensive care units (ICUs). Nevertheless, ICU doctors' preferences for supplementing oxygen are inadequately described. The aim was to identify ICU doctors' preferences for arterial oxygenation levels in mechanically ventilated adult ICU patients. METHODS: In April to August 2016, an online multiple-choice 17-part-questionnaire was distributed to 1080 ICU doctors in seven Northern European countries. Repeated reminder e-mails were sent. The study ended in October 2016. RESULTS: The response rate was 63%. When evaluating oxygenation 52% of respondents rated arterial oxygen tension (PaO2 ) the most important parameter; 24% a combination of PaO2 and arterial oxygen saturation (SaO2 ); and 23% preferred SaO2 . Increasing, decreasing or not changing a default fraction of inspired oxygen of 0.50 showed preferences for a PaO2 around 8 kPa in patients with chronic obstructive pulmonary disease, a PaO2 around 10 kPa in patients with healthy lungs, acute respiratory distress syndrome or sepsis, and a PaO2 around 12 kPa in patients with cardiac or cerebral ischaemia. Eighty per cent would accept a PaO2 of 8 kPa or lower and 77% would accept a PaO2 of 12 kPa or higher in a clinical trial of oxygenation targets. CONCLUSION: Intensive care unit doctors preferred PaO2 to SaO2 in monitoring oxygen treatment when peripheral oxygen saturation was not included in the question. The identification of PaO2 as the preferred target and the thorough clarification of preferences are important when ascertaining optimal oxygenation targets. In particular when designing future clinical trials of higher vs lower oxygenation targets in ICU patients.

The E3 ubiquitin ligase SMURF1 regulates cell-fate specification and outflow tract septation during mammalian heart development.

Smad ubiquitin regulatory factor 1 (SMURF1) is a HECT-type E3 ubiquitin ligase that plays a critical role in vertebrate development by regulating planar cell polarity (PCP) signaling and convergent extension (CE). Here we show that SMURF1 is involved in mammalian heart development. We find that SMURF1 is highly expressed in outflow tract cushion mesenchyme and Smurf1-/- mouse embryos show delayed outflow tract septation. SMURF1 is expressed in smooth muscle cells of the coronary arteries and great vessels. Thickness of the aortic smooth muscle cell layer is reduced in Smurf1-/- mouse embryos. We show that SMURF1 is a negative regulator of cardiomyogenesis and a positive regulator of smooth muscle cell and cardiac fibroblast differentiation, indicating that SMURF1 is important for cell-type specification during heart development. Finally, we provide evidence that SMURF1 localizes at the primary cilium where it may regulate bone morphogenetic protein (BMP) signaling, which controls the initial phase of cardiomyocyte differentiation. In summary, our results demonstrate that SMURF1 is a critical regulator of outflow tract septation and cell-type specification during heart development, and that these effects may in part be mediated via control of cilium-associated BMP signaling.

High efficacy of sofosbuvir/velpatasvir and impact of baseline resistance-associated substitutions in hepatitis C genotype 3 infection.

BACKGROUND: Twelve weeks of the pangenotypic direct-acting antiviral (DAA) combination sofosbuvir/velpatasvir (SOF/VEL) was highly efficient in patients with hepatitis C virus (HCV) genotype 3 (GT3) infection in the ASTRAL-3 approval study. However, presence of resistance-associated substitutions (RASs) in the HCV nonstructural protein 5A (NS5A) was associated with lower treatment response. AIM: To assess the efficacy and safety of SOF/VEL ± ribavirin (RBV) and the impact of NS5A RASs and RBV use on treatment outcome in HCV GT3 infection in a real-world setting. METHODS: In this multicentre cohort study, GT3 patients from ten treatment centres across Germany were included. Sustained virological response was assessed 12 weeks after end-of-treatment (SVR12) in modified intention-to-treat (mITT) and per-protocol analysis (PP). NS5A RASs were tested by population-based sequencing. RESULTS: A total of 293 GT3 patients were included. The median age was 48 years, 70% were male, 25.3% were cirrhotic, 9.2% were HCV/HIV co-infected and 21.8% were treatment-experienced, including 4.1% with DAA experience. Baseline NS5A RASs (Y93H, A30K, L31M) were detected in 11.2%. RBV was added in 5% of noncirrhotic and 58.9% of cirrhotic patients, respectively. SVR12 rates for SOF/VEL±RBV were 95.9% (mITT) and 99.5% (PP), respectively. Only 1 virological relapse occurred in a cirrhotic patient previously treated with SOF/RBV. No treatment-related major adverse events occurred. CONCLUSION: Twelve weeks of SOL/VEL±RBV was safe and highly efficient in HCV GT3 across a diverse patient population. Baseline NS5A RASs were rarely observed and presence did not seem to impact SVR, regardless of the use of RBV.