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Symptom response rate (≥50% reduction from baseline to EOC6 in total symptom score on the modified Myelofibrosis Symptom Assessment Form) was 27%. Grade 3-4 anemia and thrombocytopenia rates were 38% and 22%, respectively. Patients with advanced MF substantially pretreated with ruxolitinib attained robust spleen responses and reduced symptom burden with fedratinib. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.Romiplostim self-administration by patients or caregivers may offer time/cost savings to healthcare professionals (HCPs) and convenience for patients who avoid weekly clinic visits. We performed an integrated analysis of five clinical trials to evaluate the efficacy and safety of romiplostim self-administration. Data were analyzed from adults with immune thrombocytopenia (ITP) who received weekly romiplostim via self-administration or from an HCP. Patients who achieved a stable romiplostim dose for ≥3 weeks (HCP group ≥5 weeks to provide an appropriate index date to enable comparisons with the self-administration group) with platelet counts ≥50 × 109 /L were eligible. In the self-administration (n = 621) vs HCP (n = 133) groups, respectively, median age was 53 vs 58 years, median time since primary ITP diagnosis was 3.7 vs 2.5 years, and median baseline platelet count at ITP diagnosis was 19.0 vs 20.0 × 109 /L. In the self-administration and HCP-dosed groups, median romiplostim treatment duration was 89 vs 52 weeks and median total number of doses was 81 vs 50, respectively. In the self-administration and HCP groups, respectively 95.0% and 100.0% of patients achieved ≥1 platelet response (defined as weekly platelet count ≥50 × 109 /L without rescue medication in previous 4 weeks); the median percentage of weeks with a response was 94.5% and 95.9%; and rescue medication was used in 36.7% and 39.8% of patients. Self-administration did not adversely affect safety; duration-adjusted rates for all treatment-emergent adverse events (TEAEs) and bleeding TEAEs were numerically lower with self-administration. Romiplostim self-administration appears effective and well tolerated in eligible patients with ITP. © 2020 The Authors. American Journal of Hematology published by Wiley Periodicals, Inc.The diagnosis of primary plasma cell leukemia (pPCL) has been made by quantifying circulating plasma cells (cPCs) morphologically on a peripheral blood (PB) smear. However, this technique is not sufficiently sensitive. Multiparametric flow cytometry (MFC) provides a readily available and highly sensitive method to identify and quantify cPCs that could complement PB smear assessment. However, an optimal quantitative cutoff for cPCs by MFC to identify pPCL has not been established. Thus, a total of 591 patients newly diagnosed multiple myeloma (NDMM) patients who had their PB samples evaluated morphologically by PB smear and immunophenotypically by MFC prior to beginning therapy were evaluated. The presence of >200 cPCs/microliter (μL) by MFC (N = 25 or 5% of the total population) was chosen to identify patients with >5% cPCs by PB smear with a specificity of 99% and a sensitivity of 77%. AG1478 For patients with >200 cPCs/μL by MFC compared to the remainder of the cohort, the median TTNT was 18 vs. 30 months and the median OS was 38 vs. 70 months respectively. Thus, MFC assessment of PB can be utilized in conjunction with the morphological assessment of a PB smear to aid in improving the identification of pPCL among NDMM patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.This study aims to evaluate the clinical effectiveness in terms of sustained virological response (SVR), predictors of SVR and safety of available second-generation generic direct-acting antivirals in Pakistani chronic hepatitis C patients. This is a retrospective study conducted in multiple centers of Pakistan from January 2015 to January 2019. The samples include patients infected with chronic hepatitis C virus, regardless of virus genotype, cirrhosis, or prior treatment. A total of 993 patients were included in the present study, with the majority receiving sofosbuvir with daclatasvir (95%), sofosbuvir with daclatasvir and ribavirin (4%), and sofosbuvir with ribavirin (1%). There were 96% cases of chronic hepatitis, 3% cases compensated cirrhosis, and 1% cases of decompensated cirrhosis. Genotype 3 (99.6%) was the most common genotype. Overall SVR after 12 weeks was 98% for all treatment regimens. High SVR12 was observed with sofosbuvir in combination with daclatasvir (98.5%), then sofosbuvir in combination with daclatasvir and ribavirin (90.2%) and sofosbuvir in combination with ribavirin (75%). SVR rates were high in chronic hepatitis C patients (98.2%) as compared with cirrhotic patients (92.1%) and it was high in treatment-naive (98.8%) then interferon experienced patients (90.1%). In multivariate binary logistic regression analysis, patients' education status, treatment strategy, viral load, and alanine aminotransferase had a statistically significant association with SVR at 12 weeks. No major adverse events occurred which required treatment discontinuation. Generic oral direct acting antiviralss (sofosbuvir with daclatasvir) achieved higher SVR12 rates and were well tolerated in this large real-world cohort of genotype 3 infected patients. © 2020 Wiley Periodicals, Inc.The presence of a quasispecies in hepatitis E virus (HEV) infection has been documented, however, the implications of a quasispecies in HEV-host interaction are poorly understood. Here, we analyzed the whole genome sequences of a HEV 4d from the feces and liver biopsy of a patient during the icteric and convalescent phases in an acute hepatitis E infection. Viral RNAs were extracted, reversely transcribed and seven fragments encompassing the entire viral genome were amplified and cloned. By sequencing multiple colonies of each cloned viral genome amplicon with Sanger sequencing, we verified the existence of the HEV quasispecies or intra-host genetic variations within the fecal and liver biopsy samples. There were broader genetic variations in the HEV ORF1 region including the PCP, HPX, and RdRp regions during the convalescent phase whereas more genetic variations in the ORF2 P domain during the icteric phase. The quasispecies dynamics might reflect host immune pressure during viral clearance. © 2020 Wiley Periodicals, Inc.Motor actions can be suppressed with varying degrees of success, but this variability is not often captured as responses are typically represented as binary (response vs. no-response). Although the Stop/No-go P300 has been implicated as an index of inhibitory-control, it is unclear how the range of motor outputs relates to the P300. We examined the nature of this association in two experiments using an Anticipatory Timing and a Go/No-go Task, while measuring peak force, movement onset time, and P300. In both experiments, our results showed that trial-by-trial P300 amplitude on Failed Inhibitions were continuously related to peak force, where higher force (reflecting a greater degree of error) was associated with smaller P300 amplitude. Compared to Successful Inhibitions, P300 amplitude and onset latency on Failed Inhibitions were significantly reduced and delayed. Although the binary categorization of inhibition-success (Successful vs. Failed) accounts for significant variance in the P300, it misses a reliable linear relationship that can be captured by continuous measures of motor output. Overall, the results provide evidence that P300 may reflect the continuously varying engagement of inhibitory-control. We present an activation model to visualize the P300-force association and to illustrate how motor output might be modeled in the context of inhibitory-control. Our results highlight the relevance of P300 amplitude and the importance of studying the spectrum of motor output and the need for future models to account for motor output. © 2020 Society for Psychophysiological Research.BACKGROUND Tobacco smoking in pregnancy causes serious health problems for the developing fetus and mother. When used by non-pregnant smokers, pharmacotherapies (nicotine replacement therapy (NRT), bupropion, and varenicline) are effective for increasing smoking cessation, however their efficacy and safety in pregnancy remains unknown. Electronic cigarettes (ECs) are becoming widely used, but their efficacy and safety when used for smoking cessation in pregnancy are also unknown. OBJECTIVES To determine the efficacy and safety of smoking cessation pharmacotherapies and ECs used during pregnancy for smoking cessation in later pregnancy and after childbirth, and to determine adherence to smoking cessation pharmacotherapies and ECs for smoking cessation during pregnancy. SEARCH METHODS We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (20 May 2019), trial registers, and grey literature, and checked references of retrieved studies. SELECTION CRITERIA Randomised controlled trials (RCTs) conpopulation. Further research evidence on the efficacy and safety of pharmacotherapy and EC use for smoking cessation in pregnancy is needed, ideally from placebo-controlled RCTs that achieve higher adherence rates and that monitor infants' outcomes into childhood. Future RCTs of NRT should investigate higher doses than those tested in the studies included in this review. Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.The present study examined the role of attention in unconscious inhibitory visuomotor processes in three experiments that employed a mixed paradigm including a spatial cueing task and masked prime task. Spatial attention to the prime was manipulated. Specifically, the valid-cue condition (in which the prime obtained more attentional resources) and invalid-cue condition (in which the prime obtained fewer attentional resources) were included. The behavioral results showed that the negative compatibility effect (a behavioral indicator of inhibitory visuomotor processing) in the valid-cue condition was larger than that in the invalid-cue condition. Most importantly, lateralized readiness potential results indicated that the prime-related activation was stronger in the valid-cue condition than in the invalid-cue condition and that the followed inhibition in the compatible trials was also stronger in the valid-cue condition than in the invalid-cue condition. In line with the proposed attentional modulation model, unconscious visuomotor inhibitory processing is modulated by attentional resources. © 2020 Society for Psychophysiological Research.BACKGROUND Epilepsy is a common neurological disorder. In approximately 30% of epilepsy cases, seizures are uncontrolled by one antiepileptic drug (AED). These people require treatment with a combination of multiple AEDs and are described as having drug-resistant epilepsy. Oxcarbazepine is a keto-analogue of carbamazepine, an established AED, and can be used as an add-on treatment for drug-resistant epilepsy. OBJECTIVES To assess the efficacy and tolerability of oxcarbazepine as an add-on treatment for people with drug-resistant focal epilepsy. SEARCH METHODS The following databases were searched on 24 September 2018 Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy Group Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL); Medline (Ovid) 1946 to 21 September 2018; ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). Originally, we also searched SCOPUS as a substitute for Embase, but this is no longer necessary, because randomised and quasi-randomised controlled trials in Embase are now included in CENTRAL.