A noninterventional study evaluating the effectiveness of rotigotine and levodopa combination therapy in younger versus older patients with Parkinson\u27s disease

Background: PD0013 was a 6-month non-interventional study in clinical-practice comparing effectiveness and tolerability of rotigotine+levodopa in younger (<70years) vs. older (≥70years) Parkinson’s disease (PD) patients.Methods: Patients previously received levodopa for ≥6-months as monotherapy or in combination with another dopamine-agonist (DA). Primary variable: Unified PD Rating Scale (UPDRS) Part-II change from baseline to end-of-observation-period (EOP).Results: 91 younger/99 older patients started rotigotine; 68 younger/62 older patients completed the study. Most switched from levodopa+another DA. Addition of rotigotine as first DA was more common in older patients (20.2% vs.15.4%). Mean\ub1SD rotigotine-exposure: 6.1\ub13.4mg/24h younger vs. 4.9\ub12.4mg/24h older. Eleven patients changed levodopa dose during the study.At EOP, improvement in mean UPDRS-II was greater in younger patients (p=0.0289). UPDRS-II responder-rate (≥20% decrease in UPDRS-II score) was higher in younger patients (42.3% vs. 25.9%). Improvement across age-groups was similar on PD Sleep Scale-2 and Clinical Global Impressions-Improvement Scale. Adverse-drug-reactions (ADRs), and discontinuations because of ADRs, were more common among older patients. There were no new safety-signals.Conclusions: Despite low rotigotine doses, when added to levodopa or switched from levodopa+another DA, rotigotine led to greater improvement in UPDRS-II in younger patients (<70years). Assessment of individual patient data revealed clinically-meaningful improvements in UPDRS-II in both age-groups

Lacosamide monotherapy in clinical practice: A retrospective chart review

Objective: To assess effectiveness and tolerability of first-line and conversion to lacosamide monotherapy for focal seizures. Materials and Methods: Retrospective, non-interventional chart review of lacosamide monotherapy patients aged ≥16 years in Europe. Outcomes included retention rate at observational point (OP) 3 (12 ± 3 months), seizure freedom rates at OP2 (6 ± 3 months) and OP3 and adverse drug reactions (ADRs). Results: A total of 439 patients were included (98 first-line and 341 conversion to monotherapy; 128 aged ≥65 years [25 first-line and 103 conversion to monotherapy]). First-line and conversion to monotherapy retention rates were 60.2% (59/98; 95% confidence interval [CI] 49.8%-70.0%) and 62.5% (213/341; 57.1%-67.6%), respectively. Kaplan-Meier estimates of 12-month retention rates were 81.2% and 91.4% for first-line and conversion to monotherapy, respectively. First-line and conversion to monotherapy retention rates in patients aged ≥65 years were 60.0% (38.7%-78.9%) and 68.9% (59.1%-77.7%), respectively. At OP2, 66.3% of first-line and 63.0% of conversion to monotherapy patients were seizure free. At OP3, 60.2% of first-line and 52.5% of conversion to monotherapy patients were seizure free. In the ≥65 years subgroup, seizure freedom rates at OP2 were 72.0% and 68.0% for first-line and converted to monotherapy, respectively, and at OP3, 68.0% and 56.3%, respectively. Overall, 52 of 439 (11.8%) patients reported ADRs (16.4% in ≥65 years subgroup), most commonly dizziness (5.0%), headache (2.1%) and somnolence (1.6%). Conclusions: Lacosamide was effective and well tolerated as first-line or conversion to monotherapy in a clinical setting in adult and elderly patients with focal seizuresThis study was supported by UCB Pharm

Genotyping of European Toxoplasma gondii strains by a new high-resolution next-generation sequencing-based method

Purpose: A new high-resolution next-generation sequencing (NGS)-based method was established to type closely related European type II Toxoplasma gondii strains. Methods: T. gondii field isolates were collected from different parts of Europe and assessed by whole genome sequencing (WGS). In comparison to ME49 (a type II reference strain), highly polymorphic regions (HPRs) were identified, showing a considerable number of single nucleotide polymorphisms (SNPs). After confirmation by Sanger sequencing, 18 HPRs were used to design a primer panel for multiplex PCR to establish a multilocus Ion AmpliSeq typing method. Toxoplasma gondii isolates and T. gondii present in clinical samples were typed with the new method. The sensitivity of the method was tested with serially diluted reference DNA samples. Results: Among type II specimens, the method could differentiate the same number of haplotypes as the reference standard, microsatellite (MS) typing. Passages of the same isolates and specimens originating from abortion outbreaks were identified as identical. In addition, seven different genotypes, two atypical and two recombinant specimens were clearly distinguished from each other by the method. Furthermore, almost all SNPs detected by the Ion AmpliSeq method corresponded to those expected based on WGS. By testing serially diluted DNA samples, the method exhibited a similar analytical sensitivity as MS typing. Conclusion: The new method can distinguish different T. gondii genotypes and detect intra-genotype variability among European type II T. gondii strains. Furthermore, with WGS data additional target regions can be added to the method to potentially increase typing resolution

Analyse von Routinedaten zur medikamentösen Therapie von erwachsenen Patienten mit fokaler Epilepsie in Deutschland: Eine Längs- und Querschnittsanalyse neu zugelassener Antiepileptika

Objectives : The aim of this study was to investigate the antiepileptic drug (AED) treatment of adults suffering from focal epilepsies (FE) in Germany. Of special interest was the number and percentage of the patients 16 years and older receiving no treatment with an AED, treatment with one AED (monotherapy), treatment with more than one AED, and treatment with a novel AED. The definition for "novel" was newly approved at the time of market entry since 2006 (last 10 years): eslicarbazepine (ESL), lacosamide (LCM), perampanel (PER), and retigabine (RTG). Methods: The analysis was based on a claims data set covering the years 2007 to 2014, provided by AOK PLUS, a German statutory health insurance. Two patient samples were defined: (1) prevalent patients suffering from FE (at least one in- or outpatient diagnosis of FE and at least one prescription of an AED), and (2) incident FE patients (first in- or outpatient diagnosis of FE without any previous diagnoses/AED prescriptions in the preceding 6 months). Patient observation started at date of first observed inpatient or outpatient focal epilepsy diagnosis within the analyzed period.Each patient was classified as a "no AED therapy", "AED monotherapy" or "more than one AED therapy". Patients were analyzed by number and type of concomitantly prescribed AEDs in yearly tranches (no, one, two, three, four, more than four AEDs; novel versus non-novel AEDs). Results: A total of 34,422 patients diagnosed with FE aged 16 year or older (mean age 59.6 years, 48.7% female) were identified. The mean follow-up period was 1,891 days (5.2 years) since first confirmed diagnosis. The percentage of prevalent patients diagnosed with FE who received one AED (monotherapy) was stable overall and ranged between a minimum of 66.2% (2007) and a maximum of 68.9% (2010). The percentage of patients who received two AEDs ranged from 23.6% (2012) to 25.8% (2007). The remaining patients received therapies with three (6.0% in 2010 to 6.7% in 2007), four (1.0% in 2010 to 1.2% in 2009) or more than four AEDs (0.1% in 2014 to 0.3% in 2013). Between 8.1%-16.6% (2007; 2014) of the patients received no AED therapy in the observed period.In the first year after the diagnosis of FE (incident patients), 9.7% of patients didn't receive any AED therapy. Of those treated with at least one AED, 80.0% received one AED (monotherapy) only, 17.0% received therapy with two AEDs, 2.6% with three AEDs, 0.3% with four AEDs, and 0.1% with >4 AEDs during the respective observation time window and remained stable throughout the four-year follow-up period.Of prevalent patients with a diagnosis of FE, 1,889 (5.5%) received at least one prescription of a novel AED during the observation period; 98.6% of these patients received the novel AED in combination with at least one other AED. Of those patients, 269 (14.2%) received >1 novel AED. The analysis of the patients receiving novel AEDs by the time from the first confirmed diagnosis of FE until the prescription of a novel AED resulted in a mean duration of 4.0 years (SD 2.0) for ESL, 3.6 years (SD 2.2) for LCM, 5.7 years (SD 1.2) for PER, and 4.6 years (SD 0.8 years) for RTG. The mean number of AEDs prescribed before the novel AEDs were 3.2 for ESL, 2.4 for LCM, 5.0 for PER and 5.2 for RTG. Conclusions: Most patients aged 16 years or older, suffering from focal seizures, received AED monotherapy. Novel AEDs were prescribed in a small proportion of patients (<6%) and relatively late in the treatment course. These results are consistent with the recommendations of the German Society for Epileptology (Deutsche Gesellschaft für Epileptologie, DGfE) which suggests a number of monotherapy options - these options do not include the novel AEDs described in this study.Ziel: Das Ziel der vorliegenden Studie war die Beschreibung der medikamentösen Therapie von erwachsenen Patienten mit fokaler Epilepsie (FE) in Deutschland. Hierbei wurden insbesondere die Patienten analysiert, die 16 Jahre oder älter sind und keine antiepileptische Medikation, eine Monotherapie, eine Therapie mit mehr als einem Wirkstoff und/oder einem neuartigen Antiepileptikum erhielten. Für die Definition von "neuartig" wurde die Neuzulassung mit Zeitpunkt des Markteintrittes nach 2006 (in den letzten 10 Jahren) herangezogen: Eslicarbazepin (ESL), Lacosamid (LCM), Perampanel (PER) und Retigabin (RTG). Methoden: Basis für die vorliegende Studie waren anonymisierte Routinedaten aus den Jahren 2007 bis 2014 der AOK PLUS, einer deutschen gesetzlichen Krankenversicherung. Es wurden zwei Patientengruppen analysiert: (1) prävalente Patienten mit FE (mindestens eine ambulante oder stationäre Diagnose FE und mindestens eine Verordnung eines Antiepileptikums) und (2) inzidente Patienten mit FE (6 Monate vor der Erstdiagnose keine andere Epilepsiediagnose und keine Verordnung eines Antiepileptikums). Die jeweiligen Patienten wurden ab der ersten ambulanten oder stationären Diagnose mit FE innerhalb des Analysezeitraums beobachtet. Jeder Patient wurde in Hinblick auf folgende Behandlungsmuster analysiert: "keine antiepileptische Medikation", "Monotherapie" oder "Therapie mit mehr als einem antiepileptischen Wirkstoff". In der letztgenannten Gruppe wurden die Patienten nach der Anzahl und Art der verordneten antiepileptischen Wirkstoffe innerhalb eines Jahres weiter differenziert (zwei, drei, vier, mehr als vier Antiepileptika).Ergebnis: Insgesamt wurden 34.422 Patienten mit FE (Durchschnittsalter 59,6 Jahre; 48,7% weiblich) mit einer durchschnittlichen Beobachtungsdauer von 1.891 Tagen (5,2 Jahre) identifiziert. Der Anteil prävalenter Patienten, die eine Monotherapie erhielten, war über den Beobachtungszeitraum konstant mit einem Minimum von 66,2% (2007) und einem Maximum von 68,9% (2010). Der Anteil der Patienten mit zwei verordneten antiepileptischen Wirkstoffen in einem Jahr lag zwischen 23,6% (2012) und 25,8% (2007). Die verbleibenden Patienten erhielten drei (von 6,0% in 2010 bis 6,7% in 2007), vier (von 1,0% in 2010 bis 1,2% in 2009) oder mehr als vier verschiedene Antiepileptika (zwischen 0,1% in 2014 und 0,3% in 2013). Zwischen 8,1% (2007) und 16,6% (2014) der Patienten erhielten keine antiepileptische Medikation im Beobachtungszeitraum.Im ersten Jahr nach Erstdiagnose erhielten 9,7% der inzidenten Patienten keine antiepileptische Medikation. Patienten, die mindestens eine Verordnung eines Antiepileptikums erhielten, wurden zu 80,0% als Monotherapie-Patienten identifiziert, 17,0% erhielten eine Therapie mit zwei antiepileptischen Wirkstoffen, 2,6% mit drei Wirkstoffen, 0,3% mit vier Wirkstoffen und 0,1% der Patienten erhielten mehr als vier unterschiedliche Antiepileptika. Die Verteilung von Monotherapie und Therapie mit zwei oder mehr Wirkstoffen war über die gesamte vierjährige Beobachtungszeit konstant. Insgesamt erhielten 1.889 prävalenten Patienten mit FE (5,5%) mindestens eine Verordnung eines neuartigen Antiepileptikums (98,6% in Kombination mit mindestens einem anderen Antiepileptikum). Von diesen Patienten erhielten 269 Patienten (14,2%) mindestens zwei neuartige Antiepileptika. Die durchschnittliche Dauer zwischen Epilepsie-Erstdiagnose und Erstverordnung eines neuartigen antiepileptischen Wirkstoffs betrug bei ESL 4,0 Jahre (SD 2,0), bei LCM 3,6 Jahre (SD 2,2), bei PER 5,7 Jahre (SD 1,2) und RTG 4,6 Jahre (SD 0,8). Vor der Erstverordnung eines neuartigen Antiepileptikums wurden durchschnittlich 3,2 (ESL), 2,4 (LCM), 5,0 (PER) und 5,2 (RTG) andere antiepileptische Wirkstoffe verordnet. Schlussfolgerung: Die meisten Patienten mit FE im Alter von mindestens 16 Jahren erhalten eine antiepileptische Monotherapie. Neuartige Antiepileptika werden nur bei einem geringen Teil der Patienten (<6%) und relativ spät im Behandlungsverlauf verordnet. Die Ergebnisse entsprechen der deutschen Leitlinie zur Behandlung von Epilepsien (Deutsche Gesellschaft für Epileptologie, DGfE). Diese empfiehlt verschiedene Monotherapieoptionen - neuere Antiepileptika, wie in dieser Studie analysiert, sind nicht darunter

Genotyping of European Toxoplasma gondii strains by a new high-resolution next-generation sequencing-based method.

PURPOSE A new high-resolution next-generation sequencing (NGS)-based method was established to type closely related European type II Toxoplasma gondii strains. METHODS T. gondii field isolates were collected from different parts of Europe and assessed by whole genome sequencing (WGS). In comparison to ME49 (a type II reference strain), highly polymorphic regions (HPRs) were identified, showing a considerable number of single nucleotide polymorphisms (SNPs). After confirmation by Sanger sequencing, 18 HPRs were used to design a primer panel for multiplex PCR to establish a multilocus Ion AmpliSeq typing method. Toxoplasma gondii isolates and T. gondii present in clinical samples were typed with the new method. The sensitivity of the method was tested with serially diluted reference DNA samples. RESULTS Among type II specimens, the method could differentiate the same number of haplotypes as the reference standard, microsatellite (MS) typing. Passages of the same isolates and specimens originating from abortion outbreaks were identified as identical. In addition, seven different genotypes, two atypical and two recombinant specimens were clearly distinguished from each other by the method. Furthermore, almost all SNPs detected by the Ion AmpliSeq method corresponded to those expected based on WGS. By testing serially diluted DNA samples, the method exhibited a similar analytical sensitivity as MS typing. CONCLUSION The new method can distinguish different T. gondii genotypes and detect intra-genotype variability among European type II T. gondii strains. Furthermore, with WGS data additional target regions can be added to the method to potentially increase typing resolution

A ring trial to harmonize Toxoplasma gondii microsatellite typing: comparative analysis of results and recommendations for optimization

International audienceAbstract A ring trial among five European laboratories was organized to reach consistency in microsatellite (MS) typing of the zoonotic parasite Toxoplasma gondii . Three sample sets were circulated and analyzed by each laboratory following a previously published method that is based on fragment length polymorphism of 15 MS markers. The first sample set compared typing results in general and focused on effects of DNA concentration; the second sample set focused on the polymorphic fingerprinting markers that can differentiate T. gondii strains within the same archetypal lineage; and the third set focused on non-archetypal genotypes. Methodological variations between laboratories, including the software programs used to determine MS fragment length, were collated using a questionnaire. Overall, lineage-level typing results reached a high level of agreement, especially in samples with the highest DNA concentrations. However, laboratory-specific differences were observed for particular markers. Major median differences in fragment length, of up to 6 base pairs, were related to the fluorophore used to label fragment-specific primers. In addition, primer pairs with identical sequences obtained from different suppliers resulted in fragments of differing length. Furthermore, differences in the way the sequencing profiles were assessed and interpreted may have led to deviating results in fragment length determination. Harmonization of MS typing, for example, by using the same fluorophores or by numerical adjustments applied to the fragment-lengths determined, could improve the uniformity of the results across laboratories. This is the first interlaboratory comparison, providing guidelines (added as a supplement) for the optimization of this technique