Achieving clinical outcomes with benralizumab in severe eosinophilic asthma patients in a real-world setting: orbe II study.

BACKGROUND: The ORBE II study aimed to describe the characteristics and clinical outcomes of adult patients with severe eosinophilic asthma (SEA) treated with benralizumab in a real-world setting in Spain. METHODS: ORBE II (NCT04648839) was an observational, retrospective cohort study in adult SEA patients who had been prescribed benralizumab. Demographic and clinical data of 204 SEA patients were collected 12 months prior to benralizumab initiation (baseline) and at follow-up. Exacerbation rate, asthma symptoms, maintenance oral corticosteroid (OCS) use and lung function were evaluated, among other variables. RESULTS: A total of 204 SEA patients were evaluated. Mean (standard deviation, SD) age of the study population was 56.4 (12.4) years, 62.3% were women and mean (SD) duration of asthma was 15.1 (12.7) years. Median (Q1-Q3) follow-up duration was 19.5 (14.2-24.2) months. At baseline, 72.6% of the overall population (OP) presented blood eosinophil counts ≥ 300 cells/µL; 36.8% had comorbid chronic rhinosinusitis with nasal polyps (CRSwNP); 84.8% reported at least one severe exacerbation, and 29.1% were OCS-dependent. At 1 year of follow-up, patients receiving benralizumab treatment had a 85.6% mean reduction in exacerbations from baseline, and 81.4% of patients achieved zero exacerbations. We also found a clinically relevant mean (SD) increase in pre-bronchodilator (BD) FEV1 of 331 (413) mL, with 66.7% of patients achieving a pre-BD FEV1 increase ≥ 100 mL, and 46.3% of patients achieving a pre-BD FEV1 ≥ 80% of predicted. Regarding symptom control, 73.8% of the OP obtained an ACT score ≥ 20 points. After 1 year of follow-up, mean reduction in the daily OCS dose was 70.5%, and complete OCS withdrawal was achieved by 52.8% of the OCS-dependent patients. Almost half (43.7%) of the OP on benralizumab met all four criteria for clinical remission. Patients with concomitant CRSwNP obtained similar or enhanced outcomes. CONCLUSIONS: These data support the real-world benefits of benralizumab in SEA patients, and particularly in those with concomitant CRSwNP. TRIAL REGISTRATION: NCT04648839.

Long-term follow-up of HCV-infected patients with end-stage chronic kidney disease after sustained virological response with direct-acting antiviral therapy.

BACKGROUND AND AIM: Patients with chronic kidney disease (CKD) and hepatitis C infection can be safely and effectively treated with direct-acting antivirals (DAAs). However, there is scarce data on the long-term impact of hepatitis C cure on CKD. The aim of this study was to assess the long-term mortality, morbidity and hepatic/renal function outcomes in a cohort of HCV-infected individuals with CKD treated with DAAs. METHODS: 135 HCV patients with CKD stage 3b-5 who received ombitasvir/paritaprevir/ritonavir±dasabuvir in a multicenter study were evaluated for long-term hepatic and renal outcomes and their associated mortality. RESULTS: 125 patients achieved SVR and 66 were included. Prior to SVR, 53 were under renal replacement therapy (RRT) and 25 (37.8%) had liver cirrhosis. After a follow-up of 4.5 years, 25 (38%) required kidney transplantation but none combined liver-kidney. No changes in renal function were observed among the 51 patients who did not receive renal transplant although eGFR values improved in those with baseline CKD stage 3b-4. Three (5.6%) subjects were weaned from RRT. Eighteen (27.3%) patients died, mostly from cardiovascular events; 2 developed liver decompensation and 1 hepatocellular carcinoma. No HCV reinfection was observed. CONCLUSIONS: Long-term mortality remained high among end-stage CKD patients despite HCV cure. Overall, no improvement in renal function was observed and a high proportion of patients required kidney transplantation. However, in CKD stage 3b-4 HCV cure may play a positive role in renal function.

A 2-Step Strategy Combining FIB-4 With Transient Elastography and Ultrasound Predicted Liver Cancer After HCV Cure.

INTRODUCTION: Despite the direct-acting antiviral therapy has dramatically decreased the likelihood of having liver-related complications and extrahepatic outcomes, the risk of developing hepatocellular carcinoma (HCC) is not totally eliminated after sustained virological response (SVR). We aimed to develop an easy-to-apply strategy to be adopted in clinical practice for accurately classifying the HCC risk in hepatitis C virus patients after SVR. METHODS: Prospective and multicenter study enrolling hepatitis C virus patients with advanced fibrosis (transient elastography [TE] > 10 kPa) or cirrhosis by ultrasound showing SVR. They were followed up until HCC, liver transplantation, death, or until October 2020, which occurred first, with a minimum follow-up period of 6 months after SVR (follow-up: 49 [interquartile range 28-59] months). RESULTS: Patients with cirrhosis by ultrasound represented 58% (611/1,054) of the overall cohort. During the study, HCC occurrence was 5.3% (56/1,054). Multivariate analyses revealed that Fibrosis-4 (FIB-4) > 3.25 (hazard ratio [HR] 2.26 [1.08-4.73]; P = 0.030), TE (HR 1.02 [1.00-1.04]; P = 0.045) and cirrhosis by ultrasound (HR 3.15 [1.36-7.27]; P = 0.007) predicted HCC occurrence. Baseline HCC screening criteria (TE > 10 kPa or cirrhosis) identified patients at higher risk of HCC occurrence in presence of FIB-4 > 3.25 (8.8%; 44/498) vs FIB-4 < 3.25 (2.4%; 12/506), while those with only FIB > 3.25 had no HCC (0%; 0/50) (logRank 22.129; P = 0.0001). A combination of baseline FIB-4 > 3.25 and HCC screening criteria had an annual incidence >1.5 cases per 100 person-years, while the rest of the groups remained <1 case. Patients who maintained post-treatment FIB-4 > 3.25 and HCC screening criteria remained at the highest risk of HCC occurrence (13.7% [21/153] vs 4.9% [9/184]; logRank 7.396, P = 0.007). DISCUSSION: We demonstrated that a two-step strategy combining FIB-4, TE, and ultrasound could help stratify HCC incidence risk after SVR.

Effectiveness and safety of sofosbuvir/velpatasvir/voxilaprevir in patients with chronic hepatitis C previously treated with DAAs.

BACKGROUND & AIMS: Around 5% of patients with chronic hepatitis C virus (HCV) infection treated with direct-acting antiviral (DAA) agents do not achieve sustained virological response (SVR). The currently approved retreatment regimen for prior DAA failure is a combination of sofosbuvir, velpatasvir, and voxilaprevir (SOF/VEL/VOX), although there is little data on its use in clinical practice. The aim of this study was to analyse the effectiveness and safety of SOF/VEL/VOX in the real-world setting. METHODS: This was a prospective multicentre study assessing the efficacy of retreatment with SOF/VEL/VOX in patients who had experienced a prior DAA treatment failure. The primary endpoint was SVR 12 weeks after the completion of treatment (SVR12). Data on safety and tolerability were also recorded. RESULTS: A total of 137 patients were included: 75% men, 35% with liver cirrhosis. Most were infected with HCV genotype (GT) 1 or 3. The most common prior DAA combinations were sofosbuvir plus an NS5A inhibitor or ombitasvir/paritaprevir/r+dasabuvir. A total of 136 (99%) patients achieved undetectable HCV RNA at the end of treatment. Overall SVR12 was 95% in the 135 patients reaching this point. SVR12 was lower in patients with cirrhosis (89%, p = 0.05) and those with GT3 infection (80%, p <0.001). Patients with GT3 infection and cirrhosis had the lowest SVR12 rate (69%). Of the patients who did not achieve SVR12, 1 was reinfected and 7 experienced treatment failure (6 GT3, 1 GT1a). The presence of resistance-associated substitutions did not impact SVR12. Adverse effects were mild and non-specific. CONCLUSION: Real-world data show that SOF/VEL/VOX is an effective, safe rescue therapy for patients with prior DAA treatment failure despite the presence of resistance-associated substitutions. However, patients with liver cirrhosis infected by GT3 remain the most-difficult-to-treat group. LAY SUMMARY: Treatment with sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) for 12 weeks is the current recommendation for the 5% of patients infected with HCV who do not achieve eradication of the virus under treatment with direct-acting antivirals. In a Spanish cohort of 137 patients who failed a previous combination of direct-acting antivirals, a cure rate of 95% was achieved with SOF/VEL/VOX. Genotypic characteristics of the virus (genotype 3) and the presence of cirrhosis were factors that decreased the rate of cure. Treatment with SOF/VEL/VOX is an effective and safe rescue therapy due to its high efficacy and very good safety profile.

Effectiveness and safety of elbasvir/grazoprevir therapy in patients with chronic HCV infection: Results from the Spanish HEPA-C real-world cohort.

In randomized controlled trials of patients with chronic HCV infection, elbasvir/grazoprevir (EBR/GZR) demonstrated high cure rates and a good safety profile. This study assessed the effectiveness and safety of EBR/GZR, with and without ribavirin, in a real-world HCV patient cohort. HEPA-C is a collaborative, monitored national registry of HCV patients directed by the Spanish Association for the Study of the Liver and the Networked Biomedical Research Centre for Hepatic and Digestive Diseases. Patients entered into HEPA-C between December 2016 and May 2017, and treated with EBR/GZR with at least end-of-treatment response data, were included. Demographic, clinical and virologic data were analysed, and adverse events (AEs) recorded. A total of 804 patients were included in the study. The majority were male (57.9%), with a mean age of 60 (range, 19-92) years. Genotype (GT) distribution was GT 1, 86.8% (1a, 14.3%; 1b, 72.5%); GT 4, 13.2% and 176 patients (21.9%) were cirrhotic. Overall, among 588 patients with available data, 570 (96.9%) achieved sustained virologic response at 12 weeks post-treatment (SVR12). SVR12 rates by genotype were GT 1a, 97.7%; GT 1b, 98.6%; and GT 4, 98.1%. No significant differences in SVR12 according to fibrosis stage were observed. Eighty patients experienced an AE, resulting in treatment discontinuation in three. In this large cohort of patients with chronic HCV managed in a real-world setting in Spain, EBR/GZR achieved high rates of SVR12, comparable to those observed in randomized controlled trials, with a similarly good safety profile.

Impact of comorbidities on patient outcomes after interferon-free therapy-induced viral eradication in hepatitis C.

BACKGROUND & AIMS: Patients with advanced liver fibrosis remain at risk of cirrhosis-related outcomes and those with severe comorbidities may not benefit from hepatitis C (HCV) eradication. We aimed to collect data on all-cause mortality and relevant clinical events within the first two years of direct-acting antiviral therapy, whilst determining the prognostic capability of a comorbidity-based model. METHODS: This was a prospective non-interventional study, from the beginning of direct-acting antiviral therapy to the event of interest (mortality) or up to two years of follow-up, including 14 Spanish University Hospitals. Patients with HCV infection, irrespective of liver fibrosis stage, who received direct-acting antiviral therapy were used to build an estimation and a validation cohort. Comorbidity was assessed according to Charlson comorbidity and CirCom indexes. RESULTS: A total of 3.4% (65/1,891) of individuals died within the first year, while 5.4% (102/1,891) died during the study. After adjusting for cirrhosis, platelet count, alanine aminotransferase and sex, the following factors were independently associated with one-year mortality: Charlson index (hazard ratio [HR] 1.55; 95% CI 1.29-1.86; p = 0.0001), bilirubin (HR 1.39; 95% CI 1.11-1.75; p = 0.004), age (HR 1.06 95% CI 1.02-1.11; p = 0.005), international normalized ratio (HR 3.49; 95% CI 1.36-8.97; p = 0.010), and albumin (HR 0.18; 95% CI 0.09-0.37; p = 0.0001). HepCom score showed a good calibration and discrimination (C-statistics 0.90), and was superior to the other prognostic scores (model for end-stage liver disease 0.81, Child-Pugh 0.72, CirCom 0.68) regarding one- and two-year mortality. HepCom score identified low- (≤5.7 points: 2%-3%) and high-risk (≥25 points: 56%-59%) mortality groups, both in the estimation and validation cohorts. The distribution of clinical events was similar between groups. CONCLUSIONS: The HepCom score, a combination of Charlson comorbidity index, age, and liver function (international normalized ratio, albumin, and bilirubin) enables detection of a group at high risk of one- and two-year mortality, and relevant clinical events, after starting direct-acting antiviral therapy. LAY SUMMARY: The prognosis of patients with severe comorbidities may not benefit from HCV viral clearance. An algorithm to decide who will benefit from the treatment is needed to manage the chronic HCV infection better.

[The value of genetics in the era of hepatitis C triple therapy]. / Valor de la genética en la era de la terapia triple frente al virus de la hepatitis C.

Despite the introduction of protease inhibitors (PI) in the treatment of hepatitis C, the sensitivity of interferon continues to be essential to achieve a sustained virological response (SVR) and to eradicate the viral infection. Currently, pegylated interferon (PEG-IFN) and ribavirin (RBV) are required to avoid selection of PI-resistance mutations. The likelihood of obtaining an SVR with dual therapy in treatment-naïve patients with genotype 1 infection varies from 40% to 50%. That is, almost half of these patients would not require a PI, thus avoiding their adverse effects and considerably reducing the cost of the treatment. Identifying which patients could potentially respond to dual therapy is one of the main challenges in clinical practice. The genetic variability of the host is one of the main factors affecting the sensitivity of PEG-IFN and therefore in the response to current treatment. Other baseline factors related to the host, the virus and, especially, to intratreatment factors such as rapid virological response (RVR) are strongly associated with the probability of achieving an SVR. The evidence on the decision to prescribe dual or triple therapy according to the factors predictive of response is based on retrospective studies or post-hoc analyses of pivotal studies on PI. Study of the polymorphisms of the IFNL3 gene (IL28B), ITPA, IFN-stimulated genes (ISGs), TT/ΔG (ss469415590; IFNL4)) and RBV transporters could help in the decision to prescribe dual or triple therapy in treatment naïve patients.

Inhibition and working memory capacity modulate the mental space-time association.

This research aimed to investigate whether the mental space-time association of temporal concepts could be modulated by the availability of cognitive resources (in terms of working memory and inhibitory control capacities) and to explore whether access to this association could be an automatic process. To achieve this, two experiments were carried out. In Experiment 1, participants had to classify words with future and past meanings. The working memory load (high vs. low) was manipulated and the participants were grouped into quartiles according to their visuospatial working memory capacity (WMC). Temporal concepts were displayed subliminally (immediate masking) and supraliminally (delayed masking). The ANOVA showed a performance pattern consistent with the left-past right-future conceptual scheme, regardless of both the type of masking and the working memory load, except in high WMC participants, in which, interestingly, the space-time association effect was absent. In Experiment 2, participants were asked to respond to the colour of the font of the temporal words, and their attentional control capacity was assessed. The results indicated a timeline effect that was irrespective of the WM load and the type of perceptual processing, but not of the WM capacity or the inhibitory abilities. These findings partially endorse the automatic and implicit access to the mental space-time association and suggest the involvement of the availability of cognitive resources. Individual WMC differences appear to modulate the automatic nature of the effect rather than the processing conditions themselves.

Cognitive inhibition abilities explain inter-individual variability in gender-space associations.

There is a great deal of research describing the close association that exists between numerical and spatial representations, illustrating the SNARC (Spatial-Numerical Association of Response Code) effect. This effect signals the spatial mental representation of small numbers to the left and larger numbers to the right, coinciding with the direction of reading and writing. Subsequent research has found a similar spatial representation for other stimuli (e.g., size of objects and animals, and words associated with time). Some of these spatially represented stimuli are social in nature, even suggesting a spatial mental organization of stimuli based on gender (e.g., the upper part of a vertical axis for males and the lower part for females). The aim of the present study was threefold (1) to replicate and extend results on the existence of a mental gender line (as a function of response hand: female-left hand and male-right hand) when responding simply to gender of stimuli; (2) to explore the influence of inhibitory control; and, (3) to determine whether gender-space associations depend on the explicit or implicit nature of a gender task. Three experiments were designed to pursue these objectives. In Experiment 1, female, male and neutral faces and names were displayed, and the participants were asked to identify their gender. Experiment 2, which also included a Stroop task, followed the same procedure as Experiment 1, but displayed objects that could be designated as female or male and others not related to any gender. Finally, in Experiment 3, in which participants were asked to respond to the direction of an arrow, object gender was not relevant to the task. Consistent with previous research and confirming our hypotheses, the results showed a spatial mental representation of the stimuli based on gender in all three experiments, regardless of whether the stimulus was consciously perceived. Moreover, inhibitory ability showed a relationship with the gender-space line effect. The contributions and implications of this study are discussed, as are possible limitations and future lines of research.

Clockwise rotation of perspective view improves spatial recognition of complex environments in aging.

Deciphering the human spatial cognition system involves the development of simple tasks to assess how our brain works with shapes and forms. Prior studies in the mental rotation field disclosed a clockwise rotation bias on how basic stimuli are perceived and processed. However, there is a lack of a substantial scientific background for complex stimuli and how factors like sex or aging could influence them. Regarding the latter point, it is well known that our spatial skills tend to decline as we grow older. Hence, the hippocampal system is especially sensitive to aging. These neural changes underlie difficulties for the elderly in landmark orientation or mental rotation tasks. Thus, our study aimed to check whether the effect of clockwise and anticlockwise rotations in the spatial recognition of complex environments could be modulated by aging. To do so, 40 young adults and 40 old adults performed the ASMRT, a virtual spatial memory recognition test. Results showed that young adults outperformed old adults in all difficulty conditions (i.e., encoding one or three boxes positions). In addition, old adults were affected more than young adults by rotation direction, showing better performance in clockwise rotations. In conclusion, our study provides evidence that aging is particularly affected by the direction of rotation. We suggest that clockwise bias could be linked with the cognitive decline associated with aging. Future studies could address this with brain imaging measures.

Individual Differences in Working Memory Capacity Modulate Electrophysiological Correlates of Semantic Negative Priming From Single Words.

In the present study, event-related potentials (ERPs) were registered during a semantic negative priming (NP) task in participants with higher and lower working memory capacity (WMC). On each trial participants had to actively ignore a briefly presented single prime word, which was followed either immediately or after a delay by a mask. Thereafter, either a semantically related or an unrelated target word was presented, to which participants made a semantic categorization judgment. The ignored prime produced a behavioral semantic NP in delayed (but not in immediate) masking trials, and only for participants with a higher-WMC. Both masking type and WMC also modulated ERP priming effects. When the ignored prime was immediately followed by a mask (which impeded its conscious identification) a reliable N400 modulation was found irrespective of participants' WMC. However, when the mask onset following the prime was delayed (thus allowing its conscious identification), an attenuation of a late positive ERP (LPC) was observed in related compared to unrelated trials, but only in the higher-WMC group showing reliable behavioral NP. The present findings demonstrate for the first time that individual differences in WMC modulate both behavioral measures and electrophysiological correlates of semantic NP.

Spatial Recognition Memory: Differential Brain Strategic Activation According to Sex.

Human spatial memory research has significantly progressed since the development of computerized tasks, with many studies examining sex-related performances. However, few studies explore the underlying electrophysiological correlates according to sex. In this study event-related potentials were compared between male and female participants during the performance of an allocentric spatial recognition task. Twenty-nine university students took part in the research. Results showed that while general performance was similar in both sexes, the brain of males and females displayed a differential activation. Males showed increased N200 modulation than females in the three phases of memory process (encoding, maintenance, and retrieval). Meanwhile females showed increased activation of P300 in the three phases of memory process compared to males. In addition, females exhibited more negative slow wave (NSW) activity during the encoding phase. These differences are discussed in terms of attentional control and the allocation of attentional resources during spatial processing. Our findings demonstrate that sex modulates the resources recruited to performed this spatial task.

Role of Leptin in Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD), which affects about a quarter of the global population, poses a substantial health and economic burden in all countries, yet there is no approved pharmacotherapy to treat this entity, nor well-established strategies for its diagnosis. Its prevalence has been rapidly driven by increased physical inactivity, in addition to excessive calorie intake compared to energy expenditure, affecting both adults and children. The increase in the number of cases, together with the higher morbimortality that this disease entails with respect to the general population, makes NAFLD a serious public health problem. Closely related to the development of this disease, there is a hormone derived from adipocytes, leptin, which is involved in energy homeostasis and lipid metabolism. Numerous studies have verified the relationship between persistent hyperleptinemia and the development of steatosis, fibrinogenesis and liver carcinogenesis. Therefore, further studies of the role of leptin in the NAFLD spectrum could represent an advance in the management of this set of diseases.

Schizotypal personality traits and the social learning of fear.

Schizotypy can be defined as a combination of traits qualitatively similar to those found in schizophrenia, but milder in their expression, that can be found in clinical and non-clinical populations. In this research, we explore, to our knowledge, for the first time, whether schizotypal personality traits may affect the acquisition of conditioned fear by social means only. Apart from being an essential capacity to ensure learning in safe environments, social fear learning shares important characteristics with direct fear acquisition, which also makes it a great candidate for developing successful extinction procedures. Undergraduate students (n = 72) performed a task of social fear learning. In this task, participants watched a video of a person that simulated to receive electric shocks (unconditioned stimulus; US) paired with a coloured square (conditioned stimulus plus; CS+), while another coloured square was never paired (conditioned stimulus minus; CS-) with the shock. After that, they were presented with a similar sequence of coloured screens. Their Skin Conductance Responses (SCRs) were registered during the whole process. Once they finished, they completed the Schizotypal Personality Questionnaire (SPQ). Our results revealed that participants with a low score in the Cognitive-Perceptual factor of the SPQ exhibited higher SCRs when they saw the US than when they saw the CS- (all ps < 0.01) during the learning phase. Nevertheless, those with higher scores did not present any difference in their SCRs toward both stimuli (all ps > 0.05), a pattern that has been similarly found in schizophrenia. During the final trials of the test phase, participants with the highest scores in the Disorganized factor were the only ones that maintained a higher SCR towards the CS+ than towards the CS- (p = 0.006), which could be associated with an impairment in their extinction processes.

Electrophysiological correlates of the differential outcomes effect in visual short-term memory.

The differential outcomes procedure (DOP) consists in applying a specific outcome after each discriminative stimulus-correct response pairing, leading to improved performance in both memory and learning tasks (faster acquisition and/or higher response accuracy), compared to the non-differential outcomes procedure (NOP). The main aim of this study was to explore the electrophysiological correlates (ERPs) of the DOP in a visual short-term memory task, and to test whether a differential activation pattern would be observed depending on the outcomes condition (DOP vs. NOP). The ERP signals showed differences between both outcomes condition in all three phases of the short-term memory task: encoding, maintenance and retrieval. Our results are in accordance with the view that in the DOP condition the probe stimulus triggers a representation of the unique outcome, which remains active over the maintenance period (prospective process). In the NOP condition, in contrast, a representation of the probe stimulus is maintained (retrospective process). In addition, these results suggested that stimuli associated with unique outcomes captured attention involuntary at retrieval, decreasing the interference from distractor stimuli in the retrieval phase.

Implicit outcomes expectancies shape memory process: Electrophysiological evidence.

The simple manipulation of pairing specific outcomes with the sample stimuli strongly affects discriminative learning and memory processes. This procedure has been named the Differential Outcomes Procedure (DOP) and is usually compared to a control condition (the non-differential procedure, NOP) consisting in the random administration of the outcomes after each correct response. Recent research has revealed that the DOP effect arises even under unconscious conditions. In this study, we explored the temporal dynamics of short-term memory processes in both the DOP and the NOP in the absence of awareness of either the outcome (Experiment 1A) or the initial sample stimulus (Experiment 1B) through the evoked-related potentials technique. Results showed distinctive electrophysiological activation patterns in the DOP compared with the NOP at encoding, maintenance and retrieval phases. The present findings provide electrophysiological evidence of implicit-prospective processes involved in the DOP. They elucidate the processes that result in improved visual recognition memory.

Enhanced learning and retention of medical information in Alzheimer's disease after differential outcomes training.

BACKGROUND: Adherence to treatment is a crucial factor for patients who have chronic illnesses or multiple morbidities and polypharmacy, which is frequently found in older adults. The non-adherence to medications has important economic and social consequences as well as impacts on the health of the patients. One of the reasons that can explain the low adherence to treatment, is the memory deficits that are characteristics of this population and that are even more evident in cases that involve neurodegenerative diseases. METHODS AND FINDINGS: In this study, we explore whether the differential outcomes procedure (DOP), which has been shown to be useful in improving discriminative learning and memory in different populations, may facilitate learning and retention of medical recommendations in older adults who have been diagnosed with Alzheimer's disease. The results demonstrate that when this procedure was applied, the patients showed improvements in learning and long-term retention of two pill/time of day associations in a situation that simulates adherence to medical prescriptions. CONCLUSIONS: These findings contribute new data about the potential benefits of the DOP in patients with neurodegenerative disorders, highlighting the important role that this procedure could play in addressing important issues related to the health and quality of life of older adults, with or without neurodegenerative diseases, such as low adherence to medical treatments.

Semantic Negative Priming From an Ignored Single-Prime Depends Critically on Prime-Mask Inter-Stimulus Interval and Working Memory Capacity.

The aim of this study is to examine the link between working memory capacity and the ability to exert cognitive control. Here, participants with either high or low working memory capacity (WMC) performed a semantic negative priming (NP) task as a measure of cognitive control. They were required to ignore a single prime word followed by a pattern mask appearing immediately or after a delay. The prime could be semantically related or unrelated to an upcoming target word where a forced-choice categorization was required. Each type of mask (immediate vs. delayed) appeared randomly from trial to trial. Results demonstrated that, when the ignored prime was immediately followed by the mask, neither of the groups (high or low WMC) showed reliable NP. In clear contrast, when the mask onset was delayed responses latencies were reliably slower for semantically related trials than for unrelated trials (semantic NP), but only for the high WMC group. The present results clearly demonstrate that semantic NP from single ignored primes depends on both the masking pattern that follows the prime (immediate vs. delayed mask), and on working memory capacity.

Assessing Pharmacists' Preferences towards Efficacy Attributes of Disease-Modifying Therapies in Relapsing-Remitting Multiple Sclerosis.

Introduction: Hospital pharmacists are increasingly playing a critical role in the care of patients with multiple sclerosis (MS). However, little is known about their preferences and perspectives towards different attributes of disease-modifying therapies (DMTs). The objective of this research was to assess pharmacists´ preferences for DMT efficacy attributes. Methods: A multicenter, non-interventional, cross-sectional, web-based study was conducted. Preventing relapses, delaying disease progression, controlling radiological activity, and preserving health-related quality of life (HRQoL) and cognition were the attributes selected based on a literature review and a focus group with six hospital pharmacists. Conjoint analysis was used to determine preferences in eight hypothetical treatment scenarios, combining different levels of each attribute and ranking them from most to least preferred. Results: Sixty-five hospital pharmacists completed the study (mean age: 43.5 ± 7.8 years, 63.1% female, mean years of professional experience: 16.1 ± 7.4 years). Participants placed the greatest preference on delaying disease progression (35.7%) and preserving HRQoL (21.6%) and cognition (21.6%). Importance was consistent in all groups of pharmacists stratified according to demographic characteristics, experience, research background, and volume of patients seen per year. Conclusions: Understanding which treatment characteristics are meaningful to hospital pharmacists may help to enhance their synergistic role in the multidisciplinary management of patients with MS.