Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

Different aspects of illegal substance use in Catalonia : suicide, violence and evaluation of a preventive action

In Catalonia certain gaps of knowledge about health consequences related to contextual factors of illegal drug use have been identified and there is the need to assess health prevention activities implemented in the last decade. The present study aims to assess suicidal behaviors and violence among subjects using illegal substances, and to evaluate the coverage of overdose prevention programs implemented recently. Suicide risk behavior and violence were highly prevalent. Drug-scene contextual factors, including illegal/marginal income generation activities, were associated with suicidal ideation and plans (drug traffic in men and sentenced to prison in women) and violence (prison history in men and drug traffic in women). Having experienced traumatic experiences was associated with suicidal ideation and plans for both genders. Early illegal drug use was associated with victimization and offending for both genders. Overdose prevention programs coverage was considered high. Such health related problems ought to be detected in drug treatment facilities, promoting development of prevention and treatment programs.A Catalunya s'han identificat certs buits de coneixement respecte als factors contextuals de consum de drogues il·legals, i les seves conseqüències en la salut, i s’ha vist la necessitat d'avaluar activitats de prevenció implementades en l'última dècada. El present estudi té com a objectiu avaluar els comportaments suïcides i la violència entre les persones que consumeixen substàncies il·legals, i avaluar la cobertura dels programes de prevenció de sobredosi posats en marxa recentment. El risc del comportament suïcida i la violència eren altament prevalents. Els factors contextuals de les drogues, incloent les activitats de generació d'ingressos il·legals i/o marginals, es van associar amb idees i plans suïcides (el tràfic de drogues en els homes i estar condemnat a la presó en les dones) i amb la violència (estar condemnat a la presó en els homes i el tràfic de drogues a les dones). Haver patit experiències traumàtiques es va associar amb la ideació i els plans suïcides per a tots dos gèneres. El consum de drogues il·legals precoç es va associar amb la victimització i la perpetració per a tots dos generes. La cobertura dels programes de prevenció es va considerar alta. Aquest tipus de problemes de salut han de ser detectats en els centres de tractament de drogues, promocionant el desenvolupament de programes de prevenció i de tractament

Different aspects of illegal substance use in Catalonia : suicide, violence and evaluation of a preventive action

In Catalonia certain gaps of knowledge about health consequences related to contextual factors of illegal drug use have been identified and there is the need to assess health prevention activities implemented in the last decade. The present study aims to assess suicidal behaviors and violence among subjects using illegal substances, and to evaluate the coverage of overdose prevention programs implemented recently. Suicide risk behavior and violence were highly prevalent. Drug-scene contextual factors, including illegal/marginal income generation activities, were associated with suicidal ideation and plans (drug traffic in men and sentenced to prison in women) and violence (prison history in men and drug traffic in women). Having experienced traumatic experiences was associated with suicidal ideation and plans for both genders. Early illegal drug use was associated with victimization and offending for both genders. Overdose prevention programs coverage was considered high. Such health related problems ought to be detected in drug treatment facilities, promoting development of prevention and treatment programs.A Catalunya s'han identificat certs buits de coneixement respecte als factors contextuals de consum de drogues il·legals, i les seves conseqüències en la salut, i s’ha vist la necessitat d'avaluar activitats de prevenció implementades en l'última dècada. El present estudi té com a objectiu avaluar els comportaments suïcides i la violència entre les persones que consumeixen substàncies il·legals, i avaluar la cobertura dels programes de prevenció de sobredosi posats en marxa recentment. El risc del comportament suïcida i la violència eren altament prevalents. Els factors contextuals de les drogues, incloent les activitats de generació d'ingressos il·legals i/o marginals, es van associar amb idees i plans suïcides (el tràfic de drogues en els homes i estar condemnat a la presó en les dones) i amb la violència (estar condemnat a la presó en els homes i el tràfic de drogues a les dones). Haver patit experiències traumàtiques es va associar amb la ideació i els plans suïcides per a tots dos gèneres. El consum de drogues il·legals precoç es va associar amb la victimització i la perpetració per a tots dos generes. La cobertura dels programes de prevenció es va considerar alta. Aquest tipus de problemes de salut han de ser detectats en els centres de tractament de drogues, promocionant el desenvolupament de programes de prevenció i de tractament

Coverage of overdose prevention programs for opiate users and injectors: a cross-sectional study

Background. The use of opiates, particularly heroin, remains an important cause of morbidity and mortality. Half of the deaths among heroin consumers are attributed to overdose. In response to this problem, overdose prevention programs (OPPs) were designed. The objective of our study was to assess coverage of OPPs among the target population in a specific Spanish region (Catalonia) and to identify characteristics related to attendance./nMethods. A cross-sectional survey recruited individuals from outpatient treatment centers (OTCs), therapeutic communities (ThCs), and harm reduction facilities (HRFs) in Catalonia. From 513 participants, 306 opiate users and/or injectors were selected for this study. Coverage was calculated as the proportion of subjects who declared having participated in an OPP. A Poisson regression with robust variance was used to assess factors (socio-demographic aspects and psychoactive substance use patterns) associated to OPP participation, taking into account recruitment strategy./nResults. Average age of the 306 subjects was 39.7 years (s.d.: 7.7); 79% were male; 79.2% lived in urban areas and 56.3% were unemployed or had never worked. Overall OPP coverage was 43.5% (95% CI: 37%–49%). Training was received mostly in HRF (60%), followed by OTC (24.4%), prison (19%), and ThC (16%). OPP sessions were attended by 41% of Spanish-born study participants and by 63.3% of foreigners; 92.2% of the participants lived in urban areas. The Poisson regression analysis adjusted by age, sex, and type of recruitment center showed that OPP participation rates were higher for individuals with foreign nationality (PR = 1.3; 95% CI: 1.04–1.72), for those living in municipalities with more than 100,000 inhabitants (PR = 2.0; 95% CI: 1.37–2.81) or the Barcelona conurbation (PR = 2.5; 95% CI: 1.68–3.77), and for those having ever been in prison (PR = 1.6; 95% CI: 1.41–1.81) and had first consumption when they were less than 12 years old (PR = 1.2; 95% CI: 1.06–1.45)./nConclusion. Coverage as a whole can be considered high. However, in Catalonia, new strategies ought to be developed in order to attract opiate users and injectors not currently participating, by expanding OPP offer to services and regions where coverage is poor.Funding for this study was provided by the Spanish Government Grant: Instituto de Salud Carlos III-FIS PI11/01358. Further financial support was provided by the Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR 2009 SGR 718) and FIS-Redes de investigación cooperativa RD12/0028/0018

Suicidal behaviours in male and female users of illicit drugs recruited in drug treatment facilities

Objective: We assessed prevalence of suicidal ideation and plans among illicit drug users and their association with contextual factors, by gender. Methods: Cross-sectional study. In a sample of 511 illicit drug users recruited during spring 2012 in drug treatment and prevention facilities in Catalonia (Spain), the prevalence of suicidal ideation/plans in the last 12 months was assessed. Poisson regression was used to examine associations between suicidal ideation/plans and various factors (socio-demographic, psychological, illegal drug market activities and marginal income generation activities, which included any reported sex work, stealing, peddling, begging or borrowing on credit from a dealer). Results: The average age was 37.9 years (standard deviation: 8.62); 76.3% were men. Suicidal ideation/plans were reported by 30.8% of men and 38.8% of women, with no significant differences by age or gender. Recent aggression (male prevalence ratio [PR] = 2.2; female PR = 1.4), psychological treatment (male PR = 1.2; female PR = 1.3) and illegal/marginal income generation activities (male PR = 1.5; female PR = 1.1) were associated with suicidal ideation/plans. Men who trafficked were more likely to have suicidal ideation/plans (PR = 1.3), while prison history was positive for women (PR = 1.8) and negative for men (PR = 0.7). Conclusions: Prevalence of suicidal ideation/plans was high among illicit drug users recruited from healthcare facilities. Besides psychological variables, participation in illegal market activities and crime ought to be considered in drug users' suicidal prevention. Suicide risk needs to be evaluated in drug treatment facilities and psychological status and context contemplated.Objetivo: Se evaluó la prevalencia de ideación y de planes suicidas entre los/las consumidores/as de drogas ilícitas y su asociación con factores contextuales, por sexo. Métodos: Estudio transversal. En una muestra de 511 consumidores/as de drogas ilícitas, reclutados/as durante la primavera de 2012 en centros de tratamiento y preventivos de Cataluña, se evaluó la presencia de ideación o plan suicida en los últimos 12 meses. Se utilizó una regresión de Poisson para examinar las asociaciones entre la ideación o el plan suicida y diversos factores (sociodemográficos, psicológicos, mercado de drogas y actividades marginales de generación de ingresos, considerándose trabajo sexual, robo, venta ambulante, mendicidad o endeudamiento con un traficante). Resultados: La edad media fue de 37,9 años (desviación estándar: 8,62). El 76,3% eran hombres. El 30,8% de los hombres y el 38,8% de las mujeres reportaron ideación o plan suicida, sin diferencias significativas por sexo y edad. La agresión reciente (razón de prevalencia [PR] hombres = 2,2, PR mujeres = 1,4), el tratamiento psicológico (PR hombres = 1,2, PR mujeres = 1,3) y las actividades ilegales o marginales de generación de ingresos (PR hombres = 1,5, PR mujeres = 1,1) se asociaron a la ideación o plan suicida. Los hombres que traficaban eran más propensos a tener ideación o plan suicida (PR = 1,3), mientras que la prisión lo fue positivamente para las mujeres (RP = 1,8) y negativamente para los hombres (PR = 0,7). Discusión: La prevalencia de ideación o plan suicida fue alta entre los/las consumidores/as de drogas ilícitas reclutados/as en centros sanitarios. El estado psicológico, la participación en actividades de mercado y el crimen deben considerarse especialmente para la prevención del suicidio. El riesgo de suicidio debe ser evaluado en los centros de tratamiento de drogas, contemplando el estado psicológico y el contexto.Objectiu: Es va avaluar la prevalença d'ideació i de plans suïcides entre els/les consumidors/es de drogues il·lícites i la seva associació amb factors contextuals, per sexe. Mètodes: Estudi transversal. En una mostra de 511 consumidors/es de drogues il·lícites, reclutats/es durant la primavera de 2012 en centres de tractament i preventius de Catalunya, es va avaluar la presència d'ideació o pla suïcida en els últims 12 mesos. Es va utilitzar una regressió de Poisson per examinar les associacions entre la ideació o el pla suïcida i diversos factors (sociodemogràfics, psicològics, mercat de drogues i activitats marginals de generació d'ingressos, considerant treball sexual, robatori, venda ambulant, mendicitat o endeutament amb un traficant)

Violence among illicit drug users recruited in drug treatment facilities

Illicit drug use is known to be associated with injuries resulting from violence. This study aims to estimate the prevalence of violence, for the last 12 months, in illicit drug users and study the victim-offender overlap, separately by sex. Persons using illicit drugs (502) were recruited in drug treatment facilities. Violence was assessed using four questions for victim and one for perpetrator in the last 12 months. Associations between violence and socio-demographic, substance use, crime and illegal drug market aspects were examined with Poisson regression models. Victimization was reported by 49.6% men and 54.7% women; offending by 36.5% and 27.6%, respectively. Higher prevalence ratios of both victim and offender were observed among participants with marginal income generation activities and alcohol risk use. Victimization was more likely in women using parenteral route and among men with early illegal drug use, illegal polydrug use or history of imprisonment. Offending was more likely among men reporting psychological treatment, early illegal drug use, illegal polydrug use or past imprisonment, and women reporting early illegal drug use or trafficking. Thus, a high prevalence of violence (both victimization and perpetration) was found in illicit drug users, especially among those involved in market activities and crime. Drug treatment facilities should consider assessing for history and signs of violence and promote community health strategies

Suicidal behaviours in male and female users of illicit drugs recruited in drug treatment facilities

OBJECTIVE: We assessed prevalence of suicidal ideation and plans among illicit drug users and their association with contextual factors, by gender. METHODS: Cross-sectional study. In a sample of 511 illicit drug users recruited during spring 2012 in drug treatment and prevention facilities in Catalonia (Spain), the prevalence of suicidal ideation/plans in the last 12 months was assessed. Poisson regression was used to examine associations between suicidal ideation/plans and various factors (socio-demographic, psychological, illegal drug market activities and marginal income generation activities, which included any reported sex work, stealing, peddling, begging or borrowing on credit from a dealer). RESULTS: The average age was 37.9 years (standard deviation: 8.62); 76.3% were men. Suicidal ideation/plans were reported by 30.8% of men and 38.8% of women, with no significant differences by age or gender. Recent aggression (male prevalence ratio [PR]=2.2; female PR=1.4), psychological treatment (male PR=1.2; female PR=1.3) and illegal/marginal income generation activities (male PR=1.5; female PR=1.1) were associated with suicidal ideation/plans. Men who trafficked were more likely to have suicidal ideation/plans (PR=1.3), while prison history was positive for women (PR=1.8) and negative for men (PR=0.7). CONCLUSIONS: Prevalence of suicidal ideation/plans was high among illicit drug users recruited from healthcare facilities. Besides psychological variables, participation in illegal market activities and crime ought to be considered in drug users' suicidal prevention. Suicide risk needs to be evaluated in drug treatment facilities and psychological status and context contemplated

Long-term efficacy and safety of eculizumab in Japanese patients with generalized myasthenia gravis: A subgroup analysis of the REGAIN open-label extension study

The terminal complement inhibitor eculizumab was shown to improve myasthenia gravis-related symptoms in the 26-week, phase 3, randomized, double-blind, placebo-controlled REGAIN study (NCT01997229). In this 52-week sub-analysis of the open-label extension of REGAIN (NCT02301624), eculizumab's efficacy and safety were assessed in 11 Japanese and 88 Caucasian patients with anti-acetylcholine receptor antibody-positive refractory generalized myasthenia gravis. For patients who had received placebo during REGAIN, treatment with open-label eculizumab resulted in generally similar outcomes in the Japanese and Caucasian populations. Rapid improvements were maintained for 52 weeks, assessed by change in score from open-label extension baseline to week 52 (mean [standard error]) using the following scales (in Japanese and Caucasian patients, respectively): Myasthenia Gravis Activities of Daily Living (−2.4 [1.34] and − 3.3 [0.65]); Quantitative Myasthenia Gravis (−2.9 [1.98] and − 4.3 [0.79]); Myasthenia Gravis Composite (−4.5 [2.63] and − 4.9 [1.19]); and Myasthenia Gravis Quality of Life 15-item questionnaire (−8.6 [5.68] and − 6.5 [1.93]). Overall, the safety of eculizumab was consistent with its known safety profile. In this interim sub-analysis, the efficacy and safety of eculizumab in Japanese and Caucasian patients were generally similar, and consistent with the overall REGAIN population

Consistent improvement with eculizumab across muscle groups in myasthenia gravis

Objective: To assess whether eculizumab, a terminal complement inhibitor, improves patient- and physician-reported outcomes (evaluated using the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale, respectively) in patients with refractory anti-acetylcholine receptor antibody-positive generalized myasthenia gravis across four domains, representing ocular, bulbar, respiratory, and limb/gross motor muscle groups. Methods: Patients with refractory anti-acetylcholine receptor antibody-positive generalized myasthenia gravis were randomized 1:1 to receive either placebo or eculizumab during the REGAIN study (NCT01997229). Patients who completed REGAIN were eligible to continue into the open-label extension trial (NCT02301624) for up to 4 years. The four domain scores of each of the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale recorded throughout REGAIN and through 130 weeks of the open-label extension were analyzed. Results: Of the 125 patients who participated in REGAIN, 117 enrolled in the open-label extension; 61 had received placebo and 56 had received eculizumab during REGAIN. Patients experienced rapid improvements in total scores and all four domain scores of both the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale with eculizumab treatment. These improvements were sustained through 130 weeks of the open-label extension. Interpretation: Eculizumab treatment elicits rapid and sustained improvements in muscle strength across ocular, bulbar, respiratory, and limb/gross motor muscle groups and in associated daily activities in patients with refractory anti-acetylcholine receptor antibody-positive generalized myasthenia gravis