Die geopolitische Falle im Transnistrien-Konflikt

Der postsowjetische Konflikt in der Republik Moldau, besser bekannt als der Transnistrien-Konflikt, konnte 20 Jahre nach seiner Entstehung immer noch nicht gelöst werden. Das Gebiet auf dem linken Ufer des Dnjestr-Flusses hat sich infolge einer sezessionistischen Bewegung im Jahr 1992 von Moldau abgespalten und konnte durch den Aufbau eigener Herrschaftsstrukturen und mit Hilfe von außen die de facto Unabhängigkeit der Moldau verfestigen. Der eingefrorene Konflikt, der in Europa in den 90er-Jahren kaum wahrgenommen wurde, ist durch die zweite EU-Osterweiterungswelle im Jahre 2007 auf die Tagesordnung der europäischen Nachbarschaftspolitik gerückt. Die aktive Beteiligung der EU (mit Rumänien und Deutschland) und der USA in den Verhandlungen als Beobachter an der Seite der OSZE, der Russischen Föderation und der Ukraine, die eine Vermittlerrolle innehaben, stellt eine neue Grundlage für eine Konfliktreglementierung dar und sichert dementsprechend eine Ausgewogenheit der geopolitischen Interessen in diesem Teil Europas. Diese Arbeit soll, basierend auf der Geschichte, dem Verlauf der Ereignisse, der Akteursanalyse und dem Verhandlungsprozess, die Gründe für das Scheitern der Konfliktreglementierung und die Perspektiven einer Konfliktlösung erläutern

The Italian multiple sclerosis register

The past decade has seen extraordinary increase in worldwide availability of and access to several large multiple sclerosis (MS) databases and registries. MS registries represent powerful tools to provide meaningful information on the burden, natural history, and long-term safety and effectiveness of treatments. Moreover, patients, physicians, industry, and policy makers have an active interest in real-world observational studies based on register data, as they have the potential to answer the questions that are most relevant to daily treatment decision-making. In 2014, the Italian MS Foundation, in collaboration with the Italian MS clinical centers, promoted and funded the creation of the Italian MS Register, a project in continuity with the existing Italian MS Database Network set up from 2001. Main objective of the Italian MS Register is to create an organized multicenter structure to collect data of all MS patients for better defining the disease epidemiology, improving quality of care, and promoting research projects in high-priority areas. The aim of this article is to present the current framework and network of the Italian MS register, including the methodology used to improve the quality of data collection and to facilitate the exchange of data and the collaboration among national and international groups

The Italian multiple sclerosis register

The past decade has seen extraordinary increase in worldwide availability of and access to several large multiple sclerosis (MS) databases and registries. MS registries represent powerful tools to provide meaningful information on the burden, natural history, and long-term safety and effectiveness of treatments. Moreover, patients, physicians, industry, and policy makers have an active interest in real-world observational studies based on register data, as they have the potential to answer the questions that are most relevant to daily treatment decision-making. In 2014, the Italian MS Foundation, in collaboration with the Italian MS clinical centers, promoted and funded the creation of the Italian MS Register, a project in continuity with the existing Italian MS Database Network set up from 2001. Main objective of the Italian MS Register is to create an organized multicenter structure to collect data of all MS patients for better defining the disease epidemiology, improving quality of care, and promoting research projects in high-priority areas. The aim of this article is to present the current framework and network of the Italian MS register, including the methodology used to improve the quality of data collection and to facilitate the exchange of data and the collaboration among national and international groups

Disease-Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis

Objective: This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS). Methods: We retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run to confirm the results. Results: Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID-19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti-CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18-4.74, p = 0.015) with increased risk of severe COVID-19. Recent use (<1 month) of methylprednisolone was also associated with a worse outcome (OR = 5.24, 95% CI = 2.20-12.53, p = 0.001). Results were confirmed by the PS-weighted analysis and by all the sensitivity analyses. Interpretation: This study showed an acceptable level of safety of therapies with a broad array of mechanisms of action. However, some specific elements of risk emerged. These will need to be considered while the COVID-19 pandemic persists

Disease-Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis

Objective: This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS). Methods: We retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run to confirm the results. Results: Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID-19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti-CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18\u20134.74, p = 0.015) with increased risk of severe COVID-19. Recent use (<1 month) of methylprednisolone was also associated with a worse outcome (OR = 5.24, 95% CI = 2.20\u201312.53, p = 0.001). Results were confirmed by the PS-weighted analysis and by all the sensitivity analyses. Interpretation: This study showed an acceptable level of safety of therapies with a broad array of mechanisms of action. However, some specific elements of risk emerged. These will need to be considered while the COVID-19 pandemic persists. ANN NEUROL 2021;89:780\u2013789

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons

Analysis of shared common genetic risk between amyotrophic lateral sclerosis and epilepsy

Because hyper-excitability has been shown to be a shared pathophysiological mechanism, we used the latest and largest genome-wide studies in amyotrophic lateral sclerosis (n = 36,052) and epilepsy (n = 38,349) to determine genetic overlap between these conditions. First, we showed no significant genetic correlation, also when binned on minor allele frequency. Second, we confirmed the absence of polygenic overlap using genomic risk score analysis. Finally, we did not identify pleiotropic variants in meta-analyses of the 2 diseases. Our findings indicate that amyotrophic lateral sclerosis and epilepsy do not share common genetic risk, showing that hyper-excitability in both disorders has distinct origins

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons

Perspective sur les ruptures d’approvisionnement de médicaments en établissement de santé de 2006 à 2010

RÉSUMÉContexte : Si les ruptures d’approvisionnement de médicaments font partie de la réalité de la pratique pharmaceutique depuis plusieurs décennies, elles deviennent une préoccupation quotidienne pour les pharmaciens dans les années 2000 et dépassent les frontières de la littérature pharmaceutique.Objectif : L’objectif principal de cette étude était de quantifier le nombre de médicaments en rupture de stock par année et la durée de ces interruptions. L’objectif secondaire visait à décrire le nombre de médicaments en rupture de stock par fabricant et par classe thérapeutique.Méthode : Cette étude descriptive et rétrospective des ruptures d’approvisionnement en médicaments a porté sur l’ensemble des médicaments à contrat pour les hôpitaux des régions administratives de Montréal, de Laval et de l’Estrie, au Québec. Le nombre de ruptures de stocks, le nombre de jours de rupture de stock et leur durée moyenne par année ont été calculés par fabricant et par classe thérapeutique. De plus, la proportion de produits en rupture de stock et la proportion de jours de rupture de stocks ont été déterminées par classe thérapeutique. Les données ont été analysées à l’aide de tatistiques descriptives (c.-à-d. somme, moyenne, écart-type, médiane, intervalle).Résultats : Entre le 1er janvier 2006 et le 31 août 2010 (une période de 56 mois), 2400 ruptures de stocks ont été dénombrées pour un total de 258 105 jours de rupture de stocks (durée moyenne de 108 jours, écart-type de 130 jours et intervalle de 5 à 1623 jours). Un total de 70 fabricants étaient impliqués dans la survenue de toutes les ruptures d’approvisionnement de médicaments relevées durant cette période. Cinquante pour cent (50 %) des ruptures de stocks et des jours de rupture de stocks provenaient de quatre fabricants. Les interruptions étudiées touchaient la majorité des classes thérapeutiques de médicaments disponibles sur le marché. Toutefois, 50 % des ruptures de stocks provenaient de trois classes thérapeutiques (médicaments du système nerveux central, agents anti-infectieux et médicaments cardiovasculaires).Conclusion : Il s’agit des premières données canadiennes publiées sur l’étendue des ruptures d’approvisionnement sur le marché hospitalier. L’étude a démontré que les ruptures de stocks touchent la plupart des fabricants et la majorité des classes thérapeutiques. D’autres études sont nécessaires afin d’explorer les causes et les conséquences des ruptures d’approvisionnement en établissements de santé.ABSTRACTBackground: Drug shortages have been a reality of pharmacy practice for decades. However, this problem has become a daily  concern for pharmacists in the 21st century and extends beyond the pharmaceutical literature.Objective: The primary objective of this study was to quantify the annual number of drugs in short supply and the duration of these shortages. A secondary objective was to describe the number of drugs in short supply by manufacturer and therapeutic class.Method: This descriptive retrospective study examined drug shortages in relation to all hospital medication supply contracts in the administrative regions of Montréal, Laval, and the Eastern Townships in the province of Quebec. The number of inventory shortages, the number of out-of-stock days, and the mean annual duration of the shortages were calculated by manufacturer and by therapeutic class. The proportions of out-of-stock products and out-of-stock days were also calculated by therapeutic class. Descriptive statistical analyses were performed (i.e., totals, means, standard deviations, medians, and ranges).Results: There were 2400 inventory shortages between January 1, 2006, and August 31, 2010 (56-month period) for a total of 258 105 out-ofstock days (mean duration ± standard deviation 108 ± 130 days, range 5 to 1623 days). A total of 70 manufacturers were implicated in drug shortages over the study period, but 4 manufacturers were responsible for half (50%) of the shortages and out-of-stock days. The shortages affected the majority of therapeutic drug classes on the market. However, 3 therapeutic classes (central nervous system drugs, anti-infective agents, and cardiovascular drugs) accounted for 50% of the shortages.Conclusion: These are the first Canadian data published on the scope of drug shortages in the hospital market. This study has demonstrated that drug shortages affect the majority of manufacturers and most therapeutic classes. Further studies are required to explore the causes and effects of drug shortages in the hospital setting