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Background: Safinamide modulates both dopaminergic and glutamatergic systems with positive effects on motor and non-motor symptoms of Parkinson's disease (PD). The drug utilization study SYNAPSES was designed to investigate the use of safinamide in routine clinical practice, as recommended by the European Medicines Agency. Objective: To describe the occurrence of adverse events in PD patients treated with safinamide in real-life conditions. Methods: The SYNAPSES trial is an observational, European, multicenter, retrospective-prospective cohort study. Patients were followed up to 12 months with analyses performed in the overall population and in patients aged >75 years, with relevant comorbidities and with psychiatric conditions. Results: Of the 1610 patients included, 82.4% were evaluable after 12 months with 25.1% of patients >75 years, 70.8% with relevant comorbidities and 42.4% with psychiatric conditions. During observation 45.8% patients experienced adverse events, 27.7% patients had adverse drug reactions and 9.2% patients had serious adverse events. The adverse events were those already described in the patients' information leaflet. The majority were mild or moderate and completely resolved and no differences were detected between the subgroup of patients. Clinically significant improvements were seen in the UPDRS motor score and in the UPDRS total score in ≥40% of patients, according to the criteria developed by Shulman et al. Conclusion: The SYNAPSES study confirms the good safety profile of safinamide even in special groups of patients. Motor complications and motor scores improved with clinically significant results in the UPDRS scale maintained in the long-term.

Objective: Three patients with intractable Tourette syndrome (TS) underwent thalamic deep brain stimulation (DBS). To investigate the role of thalamic electrical activity in tic generation, local field potentials (LFP), EEG and EMG simultaneously were recorded. Methods: Event related potentials and event related spectral perturbations of EEG and LFP, event related cross-coherences between EEG/LFP and LFP/LFP were analyzed. As time locking events, the tic onsets were used. Spontaneous tics were compared to voluntary tic mimicking. The effect of tic suppression and DBS on thalamic LFPs was evaluated. Results: All three patients showed time-locked and prior to onset of spontaneous motor tics thalamic synchronization and thalamo-cortical cross-coherence. Also in three patients, not time-locked to motor tics, increased intra-thalamic coherences in the 1-8 Hz frequency band were found. In one patient it was demonstrated that voluntary mimicked tics were preceded by premotor cortical and thalamic potentials. In this patient unilateral thalamic DBS contralaterally decreased the background thalamic activity. Conclusions: The present study in three cases with TS shows that spontaneous tics in TS are preceded by repetitive coherent thalamo-cortical discharges, indicating that preceding a tic the basal ganglia circuits are charged up, ultimately leading to a motor tic. Significance: Thalamic LFP recording may lead to more insight in underlying pathophysiological mechanisms in TS. (c) 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Objective: Three patients with intractable Tourette syndrome (TS) underwent thalamic deep brain stimulation (DBS). To investigate the role of thalamic electrical activity in tic generation, local field potentials (LFP), EEG and EMG simultaneously were recorded. Methods: Event related potentials and event related spectral perturbations of EEG and LFP, event related cross-coherences between EEG/LFP and LFP/LFP were analyzed. As time locking events, the tic onsets were used. Spontaneous tics were compared to voluntary tic mimicking. The effect of tic suppression and DBS on thalamic LFPs was evaluated. Results: All three patients showed time-locked and prior to onset of spontaneous motor tics thalamic synchronization and thalamo-cortical cross-coherence. Also in three patients, not time-locked to motor tics, increased intra-thalamic coherences in the 1-8 Hz frequency band were found. In one patient it was demonstrated that voluntary mimicked tics were preceded by premotor cortical and thalamic potentials. In this patient unilateral thalamic DBS contralaterally decreased the background thalamic activity. Conclusions: The present study in three cases with TS shows that spontaneous tics in TS are preceded by repetitive coherent thalamo-cortical discharges, indicating that preceding a tic the basal ganglia circuits are charged up, ultimately leading to a motor tic. Significance: Thalamic LFP recording may lead to more insight in underlying pathophysiological mechanisms in TS. (c) 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Motor complications in Parkinson’s disease (PD) result from the short half-life and irregular plasma fluctuations of oral levodopa. When strategies of providing more continuous dopaminergic stimulation by adjusting oral medication fail, patients may be candidates for one of three device-aided therapies: deep brain stimulation (DBS), continuous subcutaneous apomorphine infusion, or continuous duodenal/jejunal levodopa/carbidopa pump infusion (DLI). These therapies differ in their invasiveness, side-effect profile, and the need for nursing care. So far, very few comparative studies have evaluated the efficacy of the three device-aided therapies for specific motor problems in advanced PD. As a result, neurologists currently lack guidance as to which therapy could be most appropriate for a particular PD patient. A group of experts knowledgeable in all three therapies reviewed the currently available literature for each treatment and identified variables of clinical relevance for choosing one of the three options such as type of motor problems, age, and cognitive and psychiatric status. For each scenario, pragmatic and (if available) evidence-based recommendations are provided as to which patients could be candidates for either DBS, DLI, or subcutaneous apomorphine.

Motor complications in Parkinson’s disease (PD) result from the short half-life and irregular plasma fluctuations of oral levodopa. When strategies of providing more continuous dopaminergic stimulation by adjusting oral medication fail, patients may be candidates for one of three device-aided therapies: deep brain stimulation (DBS), continuous subcutaneous apomorphine infusion, or continuous duodenal/jejunal levodopa/carbidopa pump infusion (DLI). These therapies differ in their invasiveness, side-effect profile, and the need for nursing care. So far, very few comparative studies have evaluated the efficacy of the three device-aided therapies for specific motor problems in advanced PD. As a result, neurologists currently lack guidance as to which therapy could be most appropriate for a particular PD patient. A group of experts knowledgeable in all three therapies reviewed the currently available literature for each treatment and identified variables of clinical relevance for choosing one of the three options such as type of motor problems, age, and cognitive and psychiatric status. For each scenario, pragmatic and (if available) evidence-based recommendations are provided as to which patients could be candidates for either DBS, DLI, or subcutaneous apomorphine.

Motor complications in Parkinson’s disease (PD) result from the short half-life and irregular plasma fluctuations of oral levodopa. When strategies of providing more continuous dopaminergic stimulation by adjusting oral medication fail, patients may be candidates for one of three device-aided therapies: deep brain stimulation (DBS), continuous subcutaneous apomorphine infusion, or continuous duodenal/jejunal levodopa/carbidopa pump infusion (DLI). These therapies differ in their invasiveness, side-effect profile, and the need for nursing care. So far, very few comparative studies have evaluated the efficacy of the three device-aided therapies for specific motor problems in advanced PD. As a result, neurologists currently lack guidance as to which therapy could be most appropriate for a particular PD patient. A group of experts knowledgeable in all three therapies reviewed the currently available literature for each treatment and identified variables of clinical relevance for choosing one of the three options such as type of motor problems, age, and cognitive and psychiatric status. For each scenario, pragmatic and (if available) evidence-based recommendations are provided as to which patients could be candidates for either DBS, DLI, or subcutaneous apomorphine.

Motor complications in Parkinson’s disease (PD) result from the short half-life and irregular plasma fluctuations of oral levodopa. When strategies of providing more continuous dopaminergic stimulation by adjusting oral medication fail, patients may be candidates for one of three device-aided therapies: deep brain stimulation (DBS), continuous subcutaneous apomorphine infusion, or continuous duodenal/jejunal levodopa/carbidopa pump infusion (DLI). These therapies differ in their invasiveness, side-effect profile, and the need for nursing care. So far, very few comparative studies have evaluated the efficacy of the three device-aided therapies for specific motor problems in advanced PD. As a result, neurologists currently lack guidance as to which therapy could be most appropriate for a particular PD patient. A group of experts knowledgeable in all three therapies reviewed the currently available literature for each treatment and identified variables of clinical relevance for choosing one of the three options such as type of motor problems, age, and cognitive and psychiatric status. For each scenario, pragmatic and (if available) evidence-based recommendations are provided as to which patients could be candidates for either DBS, DLI, or subcutaneous apomorphine.

Motor complications in Parkinson’s disease (PD) result from the short half-life and irregular plasma fluctuations of oral levodopa. When strategies of providing more continuous dopaminergic stimulation by adjusting oral medication fail, patients may be candidates for one of three device-aided therapies: deep brain stimulation (DBS), continuous subcutaneous apomorphine infusion, or continuous duodenal/jejunal levodopa/carbidopa pump infusion (DLI). These therapies differ in their invasiveness, side-effect profile, and the need for nursing care. So far, very few comparative studies have evaluated the efficacy of the three device-aided therapies for specific motor problems in advanced PD. As a result, neurologists currently lack guidance as to which therapy could be most appropriate for a particular PD patient. A group of experts knowledgeable in all three therapies reviewed the currently available literature for each treatment and identified variables of clinical relevance for choosing one of the three options such as type of motor problems, age, and cognitive and psychiatric status. For each scenario, pragmatic and (if available) evidence-based recommendations are provided as to which patients could be candidates for either DBS, DLI, or subcutaneous apomorphine.

Background: In The Netherlands, the state of emergency department (ED) crowding is unknown. Anecdotal evidence suggests that current ED patients experience a longer length of stay (LOS) compared to some years ago, which is indicative of ED crowding. However, no multicenter studies have been performed to quantify LOS and assess crowding at Dutch EDs. We performed this study to describe the current state of emergency departments in The Netherlands regarding patients' length of stay and ED nurse managers' experiences of crowding. Methods: A survey was sent to all 94 ED nurse managers in The Netherlands with questions regarding the type of facility, annual ED census, and patients' LOS. Additional questions included whether crowding was ever a problem at the particular ED, how often it occurred, which time periods had the worst episodes of crowding, and what measures the particular ED had undertaken to improve patient flow. Results: Surveys were collected from 63 EDs (67%). Mean annual ED visits were 24,936 (SD ± 9,840); mean LOS for discharged patients was 119 (SD ± 40) min and mean LOS for admitted patients 146 (SD ± 49) min. Consultation delays, laboratory and radiology delays, and hospital bed shortages for patients needing admission were the most cited reasons for crowding. Admitted patients had a longer LOS because of delays in obtaining inpatient beds. Thirty-nine of 57 respondents (68%) reported that crowding occurred several times a week or even daily, mostly between 12:00 and 20:00. Measures taken by hospitals to manage crowding included placing patients in hallways and using fasttrack with treatment of patients by trained nurse practitioners. Conclusions: Despite a relatively short LOS, frequent crowding appears to be a nationwide problem according to Dutch ED nurse managers, with 68% of them reporting that crowding occurred several times a week or even daily. Consultations delays, laboratory and radiology delays, and hospital bed shortage for patients needing

Background: In The Netherlands, the state of emergency department (ED) crowding is unknown. Anecdotal evidence suggests that current ED patients experience a longer length of stay (LOS) compared to some years ago, which is indicative of ED crowding. However, no multicenter studies have been performed to quantify LOS and assess crowding at Dutch EDs. We performed this study to describe the current state of emergency departments in The Netherlands regarding patients' length of stay and ED nurse managers' experiences of crowding. Methods: A survey was sent to all 94 ED nurse managers in The Netherlands with questions regarding the type of facility, annual ED census, and patients' LOS. Additional questions included whether crowding was ever a problem at the particular ED, how often it occurred, which time periods had the worst episodes of crowding, and what measures the particular ED had undertaken to improve patient flow. Results: Surveys were collected from 63 EDs (67%). Mean annual ED visits were 24,936 (SD ± 9,840); mean LOS for discharged patients was 119 (SD ± 40) min and mean LOS for admitted patients 146 (SD ± 49) min. Consultation delays, laboratory and radiology delays, and hospital bed shortages for patients needing admission were the most cited reasons for crowding. Admitted patients had a longer LOS because of delays in obtaining inpatient beds. Thirty-nine of 57 respondents (68%) reported that crowding occurred several times a week or even daily, mostly between 12:00 and 20:00. Measures taken by hospitals to manage crowding included placing patients in hallways and using fasttrack with treatment of patients by trained nurse practitioners. Conclusions: Despite a relatively short LOS, frequent crowding appears to be a nationwide problem according to Dutch ED nurse managers, with 68% of them reporting that crowding occurred several times a week or even daily. Consultations delays, laboratory and radiology delays, and hospital bed shortage for patients needing

Introduction: To prevent overcrowding of the emergency department, a flexible acute admission unit (FAAU) was created, consisting of 15 inpatient regular beds located in different departments. We expected the FAAU to result in fewer transfers to other hospitals and in a lower length of stay (LOS) of patients needing hospital admission. Methods: A before-and-after interventional study was performed in a level 1 trauma center in the Netherlands. Number of transfers and LOS of admitted ED patients in a 4-month period in 2008 (control period) and a 4-month period in 2009 (intervention period) were analyzed. Results: Of 1,619 regular admission patients, 768 were admitted in the control period and 851 in the intervention period. The number of transfers decreased from 80 (10.42%) to 54 (6.35%) (P = .0037). The mean ED LOS of both the non-admitted patients and the admitted patients needing special care significantly increased (105 minutes vs 117 minutes [P = .022] and 176 minutes vs 191 minutes [P < .001], respectively). However, the mean LOS of FAAU-admissible patients was unaltered (226 minutes vs 225 minutes, P = .865). Conclusions: The FAAU reduced the number of transfers of admitted patients to other hospitals. The increase in LOS for special care patients and non-admitted patients was not observed for regular, FAAU-admissible patients. Flexible bed management might be useful in preventing overcrowding. © 2013 Emergency Nurses Association.

Introduction: To prevent overcrowding of the emergency department, a flexible acute admission unit (FAAU) was created, consisting of 15 inpatient regular beds located in different departments. We expected the FAAU to result in fewer transfers to other hospitals and in a lower length of stay (LOS) of patients needing hospital admission. Methods: A before-and-after interventional study was performed in a level 1 trauma center in the Netherlands. Number of transfers and LOS of admitted ED patients in a 4-month period in 2008 (control period) and a 4-month period in 2009 (intervention period) were analyzed. Results: Of 1,619 regular admission patients, 768 were admitted in the control period and 851 in the intervention period. The number of transfers decreased from 80 (10.42%) to 54 (6.35%) (P = .0037). The mean ED LOS of both the non-admitted patients and the admitted patients needing special care significantly increased (105 minutes vs 117 minutes [P = .022] and 176 minutes vs 191 minutes [P < .001], respectively). However, the mean LOS of FAAU-admissible patients was unaltered (226 minutes vs 225 minutes, P = .865). Conclusions: The FAAU reduced the number of transfers of admitted patients to other hospitals. The increase in LOS for special care patients and non-admitted patients was not observed for regular, FAAU-admissible patients. Flexible bed management might be useful in preventing overcrowding. © 2013 Emergency Nurses Association.

Motor complications in Parkinson's disease (PD) result from the short half-life and irregular plasma fluctuations of oral levodopa. When strategies of providing more continuous dopaminergic stimulation by adjusting oral medication fail, patients may be candidates for one of three device-aided therapies: deep brain stimulation (DBS), continuous subcutaneous apomorphine infusion, or continuous duodenal/jejunal levodopa/carbidopa pump infusion (DLI). These therapies differ in their invasiveness, side-effect profile, and the need for nursing care. So far, very few comparative studies have evaluated the efficacy of the three device-aided therapies for specific motor problems in advanced PD. As a result, neurologists currently lack guidance as to which therapy could be most appropriate for a particular PD patient. A group of experts knowledgeable in all three therapies reviewed the currently available literature for each treatment and identified variables of clinical relevance for choosing one of the three options such as type of motor problems, age, and cognitive and psychiatric status. For each scenario, pragmatic and (if available) evidence-based recommendations are provided as to which patients could be candidates for either DBS, DLI, or subcutaneous apomorphine.

Introduction: We developed a stream system to the current triangle system in order to manage patient flow at the emergency department and to clarify ENP role boundaries. Methods: Data on admission and death rates - indicating injury severity - and data on length of stay - indicating resource utilisation - were collected from 48,397 patients triaged in the Netherlands in 2009. Results: A total of 24,294 (50.2%) patients were triaged as 'suitable for treatment by an ENP' (ENP-stream). Remaining patients were triaged 'medium care' or 'high care'. In the medium and high care groups, significantly more admissions took place (6100, 25.3%) and significantly more patients died (31, 0.1%) compared to the patient group in the ENP-stream (admissions: 840, 3.5%, . p<. 0.001 and deaths 0, 0.0%, . p<. 0.001). The ENP-streaming is an accurate predictor of not needing to be admitted (PPV. =. 97%) and of ED survival (PPV. =. 100%). Mean length of stay was significantly shorter for patients in the ENP-stream compared to the other patients (back transformed values: 74 vs. 147. min, . p<. 0.001). Conclusion: This study showed excellent correlation between the ENP-streaming and patients' injury severity and resource utilisation, suggesting high internal validity of our triage streaming system. It clarifies the ENP role, minimising the subjectivity of patient allocation. © 2011 Elsevier Ltd.

Introduction: We developed a stream system to the current triangle system in order to manage patient flow at the emergency department and to clarify ENP role boundaries. Methods: Data on admission and death rates - indicating injury severity - and data on length of stay - indicating resource utilisation - were collected from 48,397 patients triaged in the Netherlands in 2009. Results: A total of 24,294 (50.2%) patients were triaged as 'suitable for treatment by an ENP' (ENP-stream). Remaining patients were triaged 'medium care' or 'high care'. In the medium and high care groups, significantly more admissions took place (6100, 25.3%) and significantly more patients died (31, 0.1%) compared to the patient group in the ENP-stream (admissions: 840, 3.5%, . p<. 0.001 and deaths 0, 0.0%, . p<. 0.001). The ENP-streaming is an accurate predictor of not needing to be admitted (PPV. =. 97%) and of ED survival (PPV. =. 100%). Mean length of stay was significantly shorter for patients in the ENP-stream compared to the other patients (back transformed values: 74 vs. 147. min, . p<. 0.001). Conclusion: This study showed excellent correlation between the ENP-streaming and patients' injury severity and resource utilisation, suggesting high internal validity of our triage streaming system. It clarifies the ENP role, minimising the subjectivity of patient allocation. © 2011 Elsevier Ltd.

This article reports on the implementation of an adapted version of the Manchester triage system (Mackway-Jones et al 1997) in a Dutch hospital to allow trained nurse practitioners to treat patients with minor injuries or illnesses, and to assess, treat and discharge patients autonomously. The project has helped to prevent long waits in emergency departments for patients with less urgent conditions.

This article reports on the implementation of an adapted version of the Manchester triage system (Mackway-Jones et al 1997) in a Dutch hospital to allow trained nurse practitioners to treat patients with minor injuries or illnesses, and to assess, treat and discharge patients autonomously. The project has helped to prevent long waits in emergency departments for patients with less urgent conditions.

Las peroxidasas de clase III (Prxs; EC1.11.1.7) se encuentran en todas las plantas superiores. Estas Prxs participan en un amplio rango de procesos fisiológicos debido a su alto número de isoformas y a la regulación tan heterogénea de su expresión. Además, estas enzimas multifuncionales se encuentran altamente conservadas tanto entre genes parálogos como ortólogos. Este trabajo demuestra el uso efectivo de una nueva estrategia, denominada Prx-profiling, para mapear nuevos marcadores homólogos a Prxs en el genoma de cebada (Hordeum vulgare).Gracias al empleo de la nueva estrategia denominada Prx-Profiling, se han conseguido mapear un gran número de genes de Prx en el genoma de cebada, pudiéndose hablar del mapeo de un 95% de los clusters reales de Prxs en cebada.

Cost-effectiveness and cost per successful treatment has been evaluated in 186 outpatients randomised to treat moderate to severe migraine attacks either with subcutaneous sumatriptan 6 mg (n = 97) or with their current therapy (n = 89) during an open, multicentre study of 3 months. Within 2 hours, headache severity decreased to none/mild in 86% of all attacks in the sumatriptan group (STG) compared to 25% in the customary group (CTG). Migraine was alleviated earlier in the STG than in the CTG (median 3.78 vs. 13.39 hours, p < 0.0001). The direct and total cost of treatment was 133 and 2012 BF, respectively, in the CTG and 1400 and 2522 BF, respectively, in the STG. Measuring the effectiveness of earlier pain relief with sumatriptan, the incremental cost-effective ratios for direct and total cost were 132 and 53 BF per hour of relieved pain, respectively. For this price, significantly more sumatriptan patients improved their quality of life by more than 20% (61.6 vs. 20.6% patients, p < 0.001) and less sumatriptan patient consulted a medical professional (11.3 vs. 29.2% patients, p < 0.01), used less medication for adverse events (6.2 vs. 22.5%, p < 0.001) and suffered less from associated migraine symptoms. The median number of hours of diminished work-efficiency (3 vs. 7 hours, p < 0.01) or of suspension of non-professional activity (10 vs. 24 hours, p < 0.001) was also significantly lower in the STG. The total cost per successfully treated patient was lower in the STG. Sumatriptan is more effective, provides a better quality of life, reduces health care resource utilisation, and improves work productivity as compared to the CTG, thereby resulting in a favourable cost-effectiveness ratio.