Perampanel for the treatment of people with idiopathic generalized epilepsy in clinical practice.

OBJECTIVE: This study was undertaken to evaluate perampanel (PER) when used under real-world conditions to treat people with idiopathic generalized epilepsy (IGE) included in the PERaMpanel pooled analysIs of effecTiveness and tolerability (PERMIT) study. METHODS: The multinational, retrospective, pooled analysis PERMIT explored the use of PER in people with focal and generalized epilepsy treated in clinical practice across 17 countries. This subgroup analysis included PERMIT participants with IGE. Time points for retention and effectiveness measurements were 3, 6, and 12 months (last observation carried forward, defined as "last visit," was also applied to effectiveness). Effectiveness was evaluated by seizure type (total seizures, generalized tonic-clonic seizures [GTCS], myoclonic seizures, absence seizures) and included ≥50% responder rate and seizure freedom rate (defined as no seizures since at least the previous visit). Safety/tolerability was monitored throughout PER treatment and evaluated by documenting the incidence of adverse events (AEs), including psychiatric AEs and those leading to treatment discontinuation. RESULTS: The Full Analysis Set included 544 people with IGE (51.9% women, mean age = 33.3 years, mean epilepsy duration = 18.1 years). At 3, 6, and 12 months, 92.4%, 85.5%, and 77.3% of participants were retained on PER treatment, respectively (Retention Population, n = 497). At the last visit, responder and seizure freedom rates were, respectively, 74.2% and 54.6% (total seizures), 81.2% and 61.5% (GTCS), 85.7% and 66.0% (myoclonic seizures), and 90.5% and 81.0% (absence seizures) (Effectiveness Population, n = 467). AEs occurred in 42.9% of patients and included irritability (9.6%), dizziness/vertigo (9.2%), and somnolence (6.3%) (Tolerability Population, n = 520). Treatment discontinuation due to AEs was 12.4% over 12 months. SIGNIFICANCE: This subgroup analysis of the PERMIT study demonstrated the effectiveness and good tolerability of PER in people with IGE when administered under everyday clinical practice conditions. These findings are in line with clinical trial evidence, supporting PER's use as broad-spectrum antiseizure medication for the treatment of IGE.

The impact of epilepsy and antiseizure medications on sleep: Findings from a large European survey in adults with epilepsy and matched controls.

OBJECTIVE: To assess the impact of epilepsy and antiseizure medications (ASMs) on sleep quality in people with epilepsy (PWE). METHODS: An online survey was conducted in France, Germany, Italy, Spain and the UK among PWE taking >1 ASM and matched controls. Sleep quality was evaluated using the Pittsburgh Sleep Quality Index (PSQI). Associations between sleep quality (global PSQI) and overall quality of life (QoL; assessed using the 12-Item Short Form Survey [SF-12]) and sleep quality and depressive symptoms (assessed using the Neurological Disorders Depression Inventory for Epilepsy [NDDI-E]) were also evaluated. RESULTS: Overall, 500 PWE and 500 matched controls were included. PWE had significantly greater mean global PSQI scores than controls (9.32 vs 7.56; p < 0.0001), with 80% reporting a score >5 versus 66% of controls (p < 0.001). PWE experienced significantly more problems with most PSQI components than controls. Mean global PSQI scores in PWE receiving 2 versus ≥3 ASMs were 9.03 and 10.18, respectively (p < 0.004); global PSQI scores >5 were reported in 76% versus 90%, respectively (p = 0.001). Regimens containing lamotrigine or phenobarbital were associated with poorer sleep quality than those without these ASMs. In PWE, negative correlations were identified between global PSQI scores and both the SF-12 physical and mental components (Pearson's correlation coefficient [PCC], -0.61 and -0.40, respectively); NDDI-E and global PSQI scores were positively correlated (PCC, 0.6). CONCLUSIONS: PWE experience significantly worse sleep quality than people without epilepsy, with some ASMs contributing to poorer sleep. QoL and physical and mental health were all affected by sleep quality in PWE.

The impact of epilepsy on quality of life: Findings from a European survey.

INTRODUCTION: Epilepsy is a serious neurological disorder affecting the quality of life (QoL) of people with this condition. A survey was conducted in five European countries (France, Germany, Italy, Spain, and the UK) to understand the impact and burden of epilepsy and its treatment on the lives of people with epilepsy (PWE). METHODS: Five hundred PWE (taking >1 antiseizure medication [ASM]) and 500 matched controls completed a 30-minute online questionnaire. The 12-Item Short Form Survey (SF-12) was used to measure QoL and the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) was used to screen for major depressive disorder (MDD) symptoms. RESULTS: Comorbidities such as migraine, high cholesterol, osteoporosis, and Type 1 diabetes were reported more commonly in PWE, while anxiety disorders, high blood pressure, skin disorders, and mood disorders were more common in controls. However, compared to controls, a significantly higher percentage of PWE had an NDDI-E score of 15-24 (54% vs 35%; p < 0.0001), indicative of MDD symptoms. Significantly more PWE than controls were part-time employed (15% vs 11%; p = 0.03). People with epilepsy had a significantly lower total SF-12 score than controls across the physical and the mental components; compared to controls, a significantly higher proportion of PWE defined their general health as 'poor' or 'fair' and felt limited in carrying out daily and work activities. Among PWE, those taking ≥3 ASMs were more likely to experience difficulties in carrying out these activities than those on two ASMs. Ability to drive, mood, and level of self-esteem were reported as concerns for PWE. CONCLUSION: Epilepsy has a major impact on the physical and mental health of PWE, interfering with their daily and work activities and overall QoL, and its treatment might also contribute to a lower QoL. The impact of epilepsy on mood and mental health might be under-recognized.

Effectiveness, safety and tolerability of perampanel by age group when used to treat people with focal and generalized epilepsy in clinical practice: The PERMIT Extension study.

OBJECTIVE: To assess the effectiveness and safety/tolerability of perampanel (PER) in people with epilepsy (PWE) treated in everyday clinical practice for focal and generalized seizures, both in the total cohort and by age group. METHODS: The PERMIT Extension study was a pooled analysis of data from PWE included in two large previous clinical practice studies (PERMIT and PROVE). Retention was assessed over 12 months. Effectiveness was assessed based on total seizures and by seizure type (focal and generalized) after 3, 6, and 12 months of PER treatment and at final follow-up (last observation carried forward; "last visit"); assessments included responder rate (≥50% seizure frequency reduction from baseline) and seizure freedom rate (no seizures since at least the previous visit). Safety/tolerability was assessed throughout PER treatment by evaluating adverse events (AEs). All assessments were conducted for the total population and by age category (<12, ≥12 to <18, ≥18 to <65, and ≥65 years at baseline). RESULTS: Full Analysis Set included 6,822 PWE (51.1% female; mean age, 36.9 years; mean duration of epilepsy 21.4 years) with 6,433, 4,648, and 6,233 PWE assessed for retention, effectiveness, and safety/tolerability, respectively. The majority of PWE (81.1%) were aged 18-64 at baseline, with 4.5% aged <12 years, 8.4% aged 12-17 years, and 5.9% aged ≥65 years. In the overall population, retention rates at 3, 6, and 12 months were 88.0%, 77.6%, and 61.4%, respectively; responder rates at 12 months were 58.5% for total seizures, 54.6% for focal seizures, and 77.7% for generalized seizures, and corresponding seizure freedom rates were 23.6%, 19.0%, and 51.3%, respectively. PER was effective regardless of age category, although effectiveness was greatest in PWE aged ≥65 years, for both focal and generalized seizures. In the overall population, the incidence of AEs was 49.2% and the most frequent AEs (≥5% of PWE) were dizziness/vertigo (13.4%), somnolence (8.8%), irritability (7.3%), and behavioral disorders (5.3%); AEs led to treatment discontinuation in 18.3% of PWE over 12 months. The incidence of AEs and the discontinuation rate due to AEs increased with increasing age (55.0% and 23.9%, respectively, in PWE aged ≥65 years). CONCLUSION: In this study, the largest pooled analysis of PER clinical practice data conducted to date, PER was shown to be effective and generally well tolerated when used to treat people with focal or generalized epilepsy in everyday clinical practice, regardless of age category. No new or unexpected side effects emerged following long-term use in the real-world setting.

Association of Sexualized Drug Use Patterns with HIV/STI Transmission Risk in an Internet Sample of Men Who Have Sex with Men from Seven European Countries.

We estimated the prevalence of overall sexualized drug use (SDU) and of chemsex in particular, assessed patterns of drug use, and identified subpopulations of men who have sex with men (MSM) where SDU and chemsex are more frequent. Using data from an online survey of 9407 MSM recruited during 2016 in 7 European countries, we calculated the proportion of participants who reported SDU and chemsex (mephedrone, methamphetamine, and/or GHB/GBL) in the last 12 months. We grouped the different drug-use combinations in patterns and described sexual risk behaviors, sexually transmitted infections (STI), and HIV seropositivity for each one of them. Factors associated with SDU and chemsex were assessed with two logistic regression models. SDU was reported by 17.7% and chemsex by 5.2%. Risk indicators increased through the different SDU patterns but were higher within those including chemsex drugs. In the multivariate analysis, chemsex was independently associated with living in Slovenia. Both SDU and chemsex were independently associated with living in Spain; being < 50 years old; living in cities of > 500,000 inhabitants; being open about their sex life; reporting transactional sex; condomless anal intercourse; having received an STI diagnosis and with being HIV positive or having been tested ≤ 12 months ago. Magnitude of associations was higher in the chemsex model. One in five participants reported SDU, but prevalence of chemsex was notably lower. However, the risk profiles and higher prevalence of HIV/STIs among those involved in chemsex suggest the existence of a subpopulation of MSM that could be playing a relevant role in the HIV and STI epidemics, especially in very large cities of some countries.

Lisbon's COVID 19 response: harm reduction interventions for people who use alcohol and other drugs in emergency shelters.

Four emergency shelters were instituted in Lisbon during COVID-19, and are still in operation. Between March and August 2020, they served over 600 people. The shelters host a diverse population, including people experiencing homelessness, foreigners, LGBTI + people, those with reduced mobility, couples, those with pets, and People Who Use Drugs, including alcohol (henceforth PWUD). Individuals are provided care regardless of their immigration or residence status. In order to ensure continuity of care in the shelters and to bring in clients who usually refuse to be sheltered, a range of social and health interventions are integrated into the shelters. Harm reduction services ensure that the most vulnerable populations, PWUD and people experiencing homelessness, have access to the services they need. Innovations in service provision maximize the services impacts and pave the way for the future inclusion and development of these services.

Correction to: Wnt3a induces exosome secretion from primary cultured rat microglia.

Following the publication of this article [1], it has been noted by the authors that an image of the same cell nuclei has been used in error twice, in Fig. 8, parts A and B. These images are redundant in this figure as the images in parts D and E show Wnt3a treated and control cells stained with both Hoechst 33342 (as in parts A and B) and fluorescein diacetate. The data from multiple repetitions of the Hoechst 33342 stain experiment are presented in graph C. Thus, the duplicated images (in Fig. 8A and B) add no additional data and do not change the results or conclusions reached in the article. The authors apologize for any confusion this may have caused.

Potential of HIV Self-Sampling to Increase Testing Frequency Among Gay, Bisexual, and Other Men Who Have Sex With Men, and the Role of Online Result Communication: Online Cross-Sectional Study.

BACKGROUND: Late HIV diagnosis remains frequent among the gay, bisexual, and other men who have sex with men (GBMSM) population across Europe. HIV self-sampling could help remove barriers and facilitate access to testing for this high-risk population. OBJECTIVE: We assessed the capacity of HIV self-sampling to increase the testing frequency among GBMSM living in Denmark, Germany, Greece, Portugal, Romania, and Spain, and evaluated the role of new technologies in the result communication phase. METHODS: We analyzed a convenience sample of 5019 GBMSM with prior HIV testing experience who were recruited during 2016 through gay dating websites. We estimated the proportion of GBMSM who reported that the availability of self-sampling would result in an increase of their current testing frequency. We constructed a Poisson regression model for each country to calculate prevalence ratios and 95% CIs of factors associated with an increase of testing frequency as a result of self-sampling availability. RESULTS: Overall, 59% (between country range 54.2%-77.2%) of the participants considered that they would test more frequently for HIV if self-sampling was available in their country. In the multivariate analysis, the increase of testing frequency as a result of self-sampling availability was independently associated with reporting a higher number of unprotected anal intercourse events in all countries except for Greece. Independent associations were also observed among GBMSM who were not open about their sex life in Germany, Greece, Portugal, and Spain; those with a lower number of previous HIV tests in Denmark, Greece, Portugal, and Spain; and for those that took their last test more than 3 months previously in Germany, Portugal, Romania, and Spain. In addition, 58.4% (range 40.5%-73.6%) of the participants indicated a preference for learning their result through one-way interaction methods, mainly via email (25.6%, range 16.8%-35.2%) and through a secure website (20.3%, range 7.3%-23.7%). Almost two thirds (65%) of GBMSM indicated preferring one of these methods even if the result was reactive. CONCLUSIONS: Availability of HIV self-sampling kits as an additional testing methodology would lead to a much-needed increase of testing frequency, especially for the hidden, high-risk, and undertested GBMSM population. Online-based technologies without any personal interaction were preferred for the communication of the results, even for reactive results.

Brain-relevant antibodies in first-episode psychosis: a matched case-control study.

BACKGROUND: There has been much recent excitement about the possibility that some cases of psychosis may be wholly due to brain-reactive antibodies, with antibodies to N-methyl-D-aspartate receptor (NMDAR) and the voltage-gated potassium channel (VGKC)-complex reported in a few patients with first-episode psychosis (FEP). METHODS: Participants were recruited from psychiatric services in South London, UK, from 2009 to 2011 as part of the Genetics and Psychosis study. We conducted a case-control study to examine NMDAR and VGKC-complex antibody levels and rates of antibody positivity in 96 patients presenting with FEP and 98 controls matched for age and sex. Leucine-rich glioma inactiviated-1 (LGI1) and contactin-associated protein (CASPR) antibodies were also measured. Notably, patients with suspicion of organic disease were excluded. RESULTS: VGKC-complex antibodies were found in both cases (n = 3) and controls (n = 2). NMDAR antibody positivity was seen in one case and one control. Either LGI1-Abs or CASPR2-Abs were found in three cases and three controls. Neuronal antibody staining, consistent with the above results or indicating potential novel antigens, was overall positive in four patients but also in six controls. Overall, antibody positivity was at low levels only and not higher in cases than in controls. CONCLUSIONS: This case-control study of the prevalence of antibodies in FEP does not provide evidence to support the hypothesis that FEP is associated with an immune-mediated process in a subgroup of patients. Nevertheless, as other bio-clinical factors may influence the effect of such antibodies in a given individual, and patients with organic neurological disease may be misdiagnosed as FEP, the field requires more research to put these findings in context.

Economic evaluation of HIV testing for men who have sex with men in community-based organizations - results from six European cities.

The non-decreasing incidence of HIV among men who have sex with men (MSM) has motivated the emergence of Community Based Voluntary Counselling and Testing (CBVCT) services specifically addressed to MSM. The CBVCT services are characterized by facilitated access and linkage to care, a staff largely constituted by voluntary peers, and private not-for-profit structures outside the formal health system institutions. Encouraging results have been measured about their effectiveness, but these favourable results may have been obtained at high costs, questioning the opportunity to expand the experience. We performed an economic evaluation of HIV testing for MSM at CBVCT services, and compared them across six European cities. We collected retrospective data for six CBVCT services from six cities (Copenhagen, Paris, Lyon, Athens, Lisbon, and Ljubljana), for the year 2014, on the number of HIV tests and HIV reactive tests, and on all expenditures to perform the testing activities. The total costs of CBVCTs varied from 54,390€ per year (Ljubljana) to 245,803€ per year (Athens). The cost per HIV test varied from to 41€ (Athens) to 113€ (Ljubljana). The cost per HIV reactive test varied from 1966€ (Athens) to 9065€ (Ljubljana). Our results show that the benefits of CBVCT services are obtained at an acceptable cost, in comparison with the literature (values, mostly from the USA, range from 1600$ to 16,985$ per HIV reactive test in clinical and non-clinical settings). This result was transversal to several European cities, highlighting that there is a common CBVCT model, the cost of which is comparable regardless of the epidemiological context and prices. The CBVCT services represent an effective and "worth it" experience, to be continued and expanded in future public health strategies towards HIV.

Risk-taking behaviours and HIV infection among sex workers in Portugal: results from a cross-sectional survey.

OBJECTIVES: Sex workers (SW) are key populations at an increased risk of HIV infection. This study aimed to characterise risk-taking behaviours and assess HIV prevalence among SW in Portugal. METHODS: A cross-sectional survey was conducted with 1040 SW using a participatory research approach. SW were recruited in sex-work locations and community-based organisation offices. Data were collected through a questionnaire with trained interviewers. An HIV rapid test was performed in 213 respondents. RESULTS: Reported HIV prevalence was 8%: 17.6% of man-to-woman transgenders, 7.4% of women and 5% of men. Of SW reportedly living with HIV, 52.2% reported ever injecting drug use. Inconsistent condom use with clients in the last month was higher among male SW (26.5%) and with non-paying partners in the last year was higher among women (71.3%). Among reported HIV-positive SW, the proportions of inconsistent condom use were high. In multivariate regression analysis, reported HIV infection remained significantly higher among transgenders (OR 6.4; 95% CI 1.7 to 24.3), those older (OR 5.1; 95% CI 1.3 to 21.1), working outdoors (OR 5.4; 95% CI 1.9 to 15.6), having ever used psychoactive substances (OR 4.1; 95% CI 2.2 to 7.7) and earning ≤€1000 per month (OR 2.6; 95% CI 1.2 to 5.9). Of those who had an HIV rapid test, 8.9% were reactive; 73.7% were unaware of their seropositivity. CONCLUSIONS: The HIV infection burden in SW is high. Efforts to promote HIV testing must be sustained in order to reduce undiagnosed infection. The diverse risk profiles of SW must be addressed in targeted HIV interventions. Prevention interventions should be systematically implemented within most-at-risk subgroups of SW.

Perampanel for Treatment of People with a Range of Epilepsy Aetiologies in Clinical Practice: Evidence from the PERMIT Extension Study.

INTRODUCTION: It is important to assess the effectiveness of an antiseizure medication in treating different epilepsy aetiologies to optimise individualised therapeutic approaches. Data from the PERaMpanel pooled analysIs of effecTiveness and tolerability (PERMIT) Extension study were used to assess the effectiveness and safety/tolerability of perampanel (PER) when used to treat individuals with a range of epilepsy aetiologies in clinical practice. METHODS: A post hoc analysis was conducted of PERMIT Extension data from individuals with a known aetiology. Retention was assessed after 3, 6 and 12 months. Effectiveness was assessed after 3, 6 and 12 months and at the last visit (last observation carried forward). Effectiveness assessments included responder rate (≥ 50% seizure frequency reduction) and seizure freedom rate (no seizures since at least the prior visit). Safety/tolerability was assessed by evaluating adverse events (AEs) and AEs leading to discontinuation. RESULTS: PERMIT Extension included 1945 individuals with structural aetiology, 1012 with genetic aetiology, 93 with an infectious aetiology, and 26 with an immune aetiology. Retention rates at 12 months were 61.1% (structural), 65.9% (genetic), 56.8% (infectious) and 56.5% (immune). At the last visit, responder rates (total seizures) were 43.3% (structural), 68.3% (genetic), 37.0% (infectious) and 20.0% (immune), and corresponding seizure freedom rates were 15.8%, 46.5%, 11.1% and 5.0%, respectively. AE incidence rates were 58.0% (structural), 46.5% (genetic), 51.1% (infectious) and 65.0% (immune), and corresponding rates of discontinuation due to AEs over 12 months were 18.9%, 16.4%, 18.5% and 21.7%, respectively. The types of AEs reported were generally consistent across aetiology subgroups, with no idiosyncratic AEs emerging. CONCLUSION: Although PER was effective and generally well tolerated when used to treat individuals with a range of epilepsy aetiologies in clinical practice, variability in its effectiveness and tolerability across the subgroups indicates that PER may be particularly useful for individuals with specific epilepsy aetiologies.

Perampanel for the treatment of epilepsy with genetic aetiology: Real-world evidence from the PERMIT Extension study.

Genetic factors contribute to the aetiology of epilepsy in >50% of cases, and information on the use of antiseizure medications in people with specific aetiologies will help guide treatment decisions. The PERMIT Extension study pooled data from two real-world studies (PERMIT and PROVE) to investigate the effectiveness and safety/tolerability of perampanel (PER) when used to treat people with focal and generalised epilepsy in everyday clinical practice. This post-hoc analysis of PERMIT Extension explored the use of PER when used to treat individuals presumed to have epilepsy with a genetic aetiology. Assessments included retention rate (evaluated at 3, 6 and 12 months), effectiveness (responder and seizure freedom rates; evaluated at 3, 6, 12 months and the last visit [last observation carried forward) and tolerability (adverse events [AEs]). Of the 6822 people with epilepsy included in PERMIT Extension, 1012 were presumed to have a genetic aetiology. The most common genetic aetiologies were idiopathic generalised epilepsy (IGE; 58.2%), tuberous sclerosis (1.1%), Dravet syndrome (0.8%) and genetic epilepsy with febrile seizures plus (GEFS+; 0.5%). Retention rates at 3, 6 and 12 months in the total genetic aetiology population were 89.3%, 79.7% and 65.9%, respectively. In the total genetic aetiology population, responder rates at 12 months and the last visit were 74.8% and 68.3%, respectively, and corresponding seizure freedom rates were 48.9% and 46.5%, respectively. For the specific aetiology subgroups, responder rates at 12 months and the last visit were, respectively: 90.4% and 84.4% (IGE), 100% and 57.1% (tuberous sclerosis), 100% and 71.4% (Dravet syndrome), and 33.3% and 20.0% (GEFS+). Corresponding seizure freedom rates were, respectively: 73.1% and 64.6% (IGE), 33.3% and 22.2% (tuberous sclerosis), 20.0% and 28.6% (Dravet syndrome), and 0% and 0% (GEFS+). The incidence of AEs was 46.5% for the total genetic aetiology population, 48.8% for IGE, 27.3% for tuberous sclerosis, 62.5% for Dravet syndrome, and 20% for GEFS+. Tolerability findings were consistent with PER's known safety profile. PER was effective and generally well tolerated when used in individuals with a presumed genetic epilepsy aetiology in clinical practice. PER was effective across a wide range of genetic aetiologies.

Problemas ligados ao álcool em centros de emergência (PLACE)-People experiencing homelessness with alcohol-related problems in Lisbon's emergency shelters during the COVID-19 pandemic: a description and analysis of a harm reduction intervention.

Introduction: Alcohol-related problems disproportionally affect people experiencing homelessness. As the first wave of the COVID-2019 pandemic spread in 2020, a number of emergency shelters were opened in Lisbon. Increased difficulties in obtaining alcohol could have led to an increased incidence of alcohol withdrawal. Therefore, a low-threshold harm reduction intervention was introduced to these emergency shelters. This consisted of a fixed medication treatment, made available immediately for those with specific conditions, without the need for a medical evaluation or abstinence from alcohol, together with an offer of subsequent access to specialized addiction centers. The Problemas Ligados ao Álcool em Centros de Emergência (PLACE) study (alcohol-related problems in emergency shelters) is a retrospective mixed-methods observational study. It describes the demographic, health, and social characteristics of shelter users participating in the program and aims to evaluate the intervention as well as the experience of the patients, professionals, and decision-makers involved. Results: A total of 69 people using shelters self-reported alcohol-related problems. Among them, 36.2% of the people accepted a pharmacological intervention, and 23.2% selected an addiction appointment. The take-up of the intervention was associated with better housing outcomes. A description of an individual's trajectory after leaving the shelter is provided. Discussion: This study suggests that non-abstinence-focused interventions can be useful and well-tolerated in treating addiction in this population.

Unmet needs of people with epilepsy: A qualitative study exploring their journey from presentation to long-term management across five European countries.

Introduction: Epilepsy is a neurological disease that can negatively impact a person's physical, psychological, social, and emotional well-being. The aim of this study was to provide insights into the experiences of people with epilepsy on polytherapy (i.e., people on a combination of two or more anti-seizure medications [ASMs]), with an emphasis on their emotional journey. Methods: Market research was conducted with 40 people with epilepsy from France, Germany, Italy, Spain, and the United Kingdom. Semi-structured interviews were analyzed using both a content and framework analysis approach. A content analysis of participants' expressed emotions was used to illustrate the changes of emotions experienced by people with epilepsy from presentation through to monitoring and follow-up stages. Results: In each stage of the journey, themes and subthemes were identified under the overarching headings: Stage 1: Presentation - Life is turned upside down; Stage 2: Diagnosis - Period of learning; Stage 3: Treatment - Aspirations and experimentation; and Stage 4: Monitoring and follow-up - Feeling "out on a limb". The research identified key unmet needs and opportunities for people with epilepsy to improve their subjective experiences at different stages of their disease journey, namely: (1) establish and promote support networks from presentation through to monitoring and follow-up stages; (2) accelerate pathway to diagnosis; (3) provide opportunities to discuss the diagnosis with patients; (4) clarify treatment-change guidelines for patients; and (5) develop a shared treatment decision-making/empowerment tool. Discussion: The research findings and recommendations have the potential to drive change at an individual level, as well as at a healthcare level.

Perampanel outcomes at different stages of treatment in people with focal and generalized epilepsy treated in clinical practice: Evidence from the PERMIT study.

Introduction: The PERMIT study is the largest pooled analysis of perampanel (PER) clinical practice data conducted to date. Methods: This post-hoc analysis of PERMIT investigated the effectiveness, safety and tolerability of PER when used as early add-on therapy (after failure of one or two previous antiseizure medications) in comparison with late add-on therapy (after failure of three or more previous antiseizure medications). Retention and effectiveness were assessed after 3, 6, and 12 months, and at the last visit (last observation carried forward). Effectiveness was assessed by seizure type (total seizures, focal seizures, generalized tonic-clonic seizures [GTCS]) and assessments included seizure freedom rate and responder rate. Safety and tolerability were assessed by evaluating adverse events (AEs) and discontinuation due to AEs. Results: The Full Analysis Set included 1184 and 2861 PWE treated with PER as early and late add-on therapy, respectively. Compared to the late add-on subgroup, the early add-on subgroup was characterized by later mean age at epilepsy onset, shorter mean duration of epilepsy, lower rates of intellectual disability and psychiatric comorbidity, and lower frequency of seizures per month, suggesting a less severe form of epilepsy in this subgroup. After 12 months, retention was significantly higher in the early versus late add-on subgroup (67.7% vs. 62.4%; p = 0.004). At the last visit, responder rates in the early versus late add-on subgroup were significantly higher for total seizures (68.2% vs. 39.3%; p < 0.001), focal seizures (65.0% vs. 36.8%; p < 0.001) and GTCS (83.7% vs. 67.2%; p < 0.001), as were seizure freedom rates (total seizures, 35.9% vs. 11.9% [p < 0.001]; focal seizures, 29.4% vs. 8.7% [p < 0.001]; GTCS, 69.0% vs. 48.1% [p < 0.001]). Incidence of AEs was significantly lower in the early versus late add-on subgroup (42.1% vs. 54.7%; p < 0.001), as was the rate of discontinuation due to AEs over 12 months (15.0% vs. 18.1%; p = 0.031). Discussion: This study demonstrated that PER was effective and generally well tolerated when initiated as early or late add-on therapy, but it was significantly more effective and better tolerated when initiated early. These findings support PER's use as a broad-spectrum, early add-on therapy for use in PWE with focal and generalized seizures.

Wnt3a induces exosome secretion from primary cultured rat microglia.

BACKGROUND: Microglia, the immune effector cells of the CNS and the signaling molecule Wnt, both play critical roles in neurodevelopment and neurological disease. Here we describe the inducible release of exosomes from primary cultured rat microglia following treatment with recombinant carrier-free Wnt3a. RESULTS: Wnt3a was internalised into microglia, being detectable in early endosomes, and secreted in exosomes through a GSK3-independent mechanism. Electron microscopy demonstrated that exosomes were elliptical, electron-dense (100 nm) vesicles that coalesced with time in vitro. In contrast to microglia, primary cortical neurons released exosomes constitutively and the quantity of exosomes released was not altered by Wnt3a treatment. The proteomic profile of the microglial-derived exosomes was characterised using liquid chromatography-tandem mass spectrometry (LC/MS/MS) and the vesicles were found to be associated with proteins involved in cellular architecture, metabolism, protein synthesis and protein degradation including ß-actin, glyceraldehyde-3-phosphate dehydrogenase, ribosomal subunits and ubiquitin (45 proteins in total). Unlike lipopolysaccharide, Wnt3a did not induce a neurotoxic, pro-inflammatory phenotype in primary microglia. CONCLUSION: These findings reveal a novel mechanism through which Wnt3a signals in microglia resulting in the release of exosomes loaded with proteinaceous cargo.

Sexual behaviour patterns and STI risk: results of a cluster analysis among men who have sex with men in Portugal.

OBJECTIVES: Portugal has the highest HIV incidence rate in Western Europe. The proportion assigned to sexual contact between men recently increased to more than 30% of all HIV infections. Men who have sex with men (MSM) are vulnerable to the acquisition of other sexually transmitted infections (STIs), increasing the per-contact risk of HIV infection. Building on syndemic theory, the aim of this analysis was to identify patterns of current sexual behaviour in MSM, and explore their relationship with self-reported current, past STI diagnoses and HIV positive serostatus. DESIGN: A cross-sectional behavioural survey was conducted in Portugal among MSM, using a community-based participatory research approach. Hierarchical cluster analysis was used to identify patterns including behavioural and demographic factors. RESULTS: The analysis resulted in six clusters. Three clusters showed higher rates of current STI diagnosis (ranging from 11.7% to 17.1%), past STI diagnosis (ranging from 25.5% to 41.5%) and HIV positive serostatus (ranging from 13.0% to 16.7%). From the three clusters scoring lower on current and past STI and HIV diagnoses, one was characterised by a high number of sexual partners (62% had more than 12 partners in the last year), a high proportion (94.6%) of frequent visits to gay venues to meet sexual partners and high alcohol use (46.1%). The other two clusters scored lower on high risk sexual behaviour. CONCLUSION: Factors other than sexual behaviour appear to reinforce the vulnerability to STIs and HIV of some MSM in this study, suggesting a syndemic of STIs, HIV and other adverse conditions. More research is needed to better understand the drivers of the STI/HIV epidemic in Portuguese MSM, using a concept that goes beyond risk behaviour, to develop effective combination prevention interventions.

Preference towards HIV Self-Testing above Other Testing Options in a Sample of Men Who Have Sex with Men from Five European Countries.

We analyzed men who have sex with men (MSM) from Denmark, Germany, Greece, Portugal and Spain to identify who would choose HIV self-testing as their preferred testing method and assessed their preferred setting to acquire a self-testing kit and to confirm a reactive result. In 2016, we recruited an online sample of 3725 HIV-negative MSM. We used Poisson regression to identify factors associated with choosing self-testing as the preferred testing option. For those choosing it as their preferred option, we assessed the preferred settings to acquire a self-testing kit and to confirm a reactive result. Not being open about one's sexual behaviors with men was associated with choosing self-testing as the preferred option, except in Greece; older age in Greece and Spain; reporting condomless anal intercourses (CAI) in Germany and Portugal; reporting one previous test in Greece; between 2 and 5 in Spain and with having been tested ≥ 12 months ago in Germany, Portugal and Spain. The internet (32.8%) was the preferred place to acquire a self-testing kit and primary care (34.0%) for confirmation purposes. Self-testing was highly valued, especially among individuals who were not open about their sexual behaviors with men. In certain countries, it was also associated with older age, CAI and being undertested.

Smoked cocaine in socially-depressed areas.

BACKGROUND: The main objectives of this study are to describe the smoked cocaine user's profile in socially-depressed areas and their needs from a harm-reduction perspective, to investigate their use of smoking crack and compare the acute effects between injecting and smoking consumption. METHODS: The study took place in SAPS, Barcelona, Spain. Two focus group sessions were undertaken with a total of 8 drug users. Secondly, the 8 participants answered a structured questionnaire and in the course of the sessions, as a snowball activity, were trained to survey 6 other crack smokers. RESULTS: We obtained 56 questionnaires. The majority of participants were from non-European Community countries (62.69%), 70.2% of participants referred to sharing the smoking equipment. The most frequent symptoms reported during smoked cocaine were mydriasis (83.33%)), perspiration (72.92%) and compulsive object search (70.83%) During the group sessions, participants said that smoked cocaine is much more addictive than injected cocaine and causes more anxiety. Participants also reported the difficulty of changing from injected use to smoked use, due to the larger amount of cocaine needed to reach the same effects as when having injected. CONCLUSIONS: We can conclude that the research, focused on achieving greater knowledge of the smoked cocaine user's profile, their usage of smoking crack, consumption patterns and acute effects, should be incorporated into substance misuse interventions.