Mais la polymyxine n'est pas du tout absorbée dans le sang du système gastro-intestinal et n'a d'effet que dans l'intestin et est utile pour le traitement des infections intestinales amoxicilline prix Internet en y faisant des achats permettant d’économiser jusqu'à soixante-dix pour cent, tout en étant sûr de la qualité des produits pharmaceutiques.
Effect of rasagiline on sleep disturbances and fatigue in patients
with Parkinson’s disease: a pilot study
T Müller1, M Klasser2, J Rieke3, S Ries4, G Schwartz5, R Ehret6, and the Rasagiline Sleep Disturbances Study Group*
1Department of Neurology, St Joseph Hospital Berlin-Weissensee, Germany; 2GWD Consult, Mühlheim, Germany; 3Private practice, Giessen, Germany; 4Private practice, Erbach, Germany;
5Private practice, Hamburg, Germany; 6Private practice, Berlin, Germany; *S Bittkau (Karlstadt), W Kohlhepp (Bad Waldsee), M Müngersdorf (Berlin)
■ At the final evaluation, physicians were asked to globally rate the
Figure 2: Percentage improvement in median PDSS scores from
efficacy, and also the tolerability, of rasagiline as ‘very good’, ‘good’,
baseline to final evaluation
Rasagiline is a potent, highly selective,
irreversible, monoamine oxidase type-B (MAO-B) inhibitor. Once-
■ Safety analyses included the incidence of adverse drug reactions
daily rasagiline (1 mg) is indicated for the treatment of idiopathic
(ADRs; events judged to be likely, unlikely, or possibly related to the
Parkinson’s disease (PD) as monotherapy, or as adjunct therapy (with
levodopa) in patients with end-of-dose fluctuations. In this pilot study,
the efficacy and tolerability of rasagiline was assessed under
everyday practice conditions, with particular focus on PD-related
■ Differences between time points were assessed using Student’s t
sleep disturbances, and the occurrence of fatigue.
to compare mean differences between metric data for dependent
In this 8-week, multicentre study, 26 patients with
samples. Missing data at endpoint were imputed using the last
idiopathic PD received treatment with rasagiline according to their
observation carried forward (LOCF) method.
physicians’ recommendations. Study visits were at baseline,
~4 weeks and ~8 weeks. Efficacy measures included PD Sleep
■ The fact that the study was observational, with no explicit hypotheses,
Scale (PDSS), Fatigue Severity Scale (FSS), and the physician’s
should be taken into consideration when interpreting the results of the
global efficacy rating at endpoint. Adverse drug reactions (ADRs),
and the physician’s global tolerability rating were also recorded.
Overall, 23/26 patients received rasagiline as combination
therapy (missing data, n=3) – most commonly with levodopa
preparations (91%) and dopamine agonists (87%). Baselinecharacteristics were: 58% male; mean age (± SD) 66.3 ± 8.2 years;
mean disease duration 6.8 ± 4.2 years; Hoehn & Yahr stages I (15%),
■ Data were collected from 26 patients with idiopathic PD who received
■ According to FSS measures, the proportion of patients suffering from
II (42%), III (39%), IV (4%). From baseline to final evaluation, there
fatigue (i.e., mean score per item of ≥4) decreased from 71% to 58%
were marked improvements in median PDSS total score (12%), andin the individual PDSS items of maintenance insomnia (200%), sleep
■ Overall, 23/26 patients received rasagiline as combination therapy
over the course of the study (Figure 3).
refreshment (54%), sleep quality (46%), and nocturnal restlessness
(missing data, n=3) – most commonly with levodopa preparations
■ The median FSS score also fell from 4.9 to 4.2 over the 8-week study
(29%). Other items, including nocturnal psychosis, showed no
worsening with rasagiline treatment. According to FSS measures, theproportion of patients reporting fatigue decreased from 71% to 58%
■ Patient baseline characteristics are shown in Table 1. Most patients
over the course of the study. At final evaluation, over half (57%) of
were in Hoehn & Yahr stages II and III (i.e., bilateral symptoms with or
Figure 3: Frequency of FSS scores indicating fatigue or no fatigue,
physicians rated the efficacy of rasagiline as ‘good/very good’.
rated at baseline and final evaluation
Overall, 24/26 (92%) patients experienced no ADRs, and 79% ofphysicians rated tolerability as ‘good/very good’.
■ Median treatment duration with rasagiline was 62 days.
In this small-scale study of daily clinical practice, PD
patients treated with rasagiline reported improved quality of sleep,
Table 1: Patient baseline characteristics
■ Rasagiline is a potent, highly selective, irreversible, second-generation,
monoamine oxidase type-B (MAO-B) inhibitor.
■ Once-daily rasagiline (1 mg) is indicated for the treatment of idiopathic
Parkinson’s disease (PD) as monotherapy, or as adjunct therapy (with
levodopa) in patients with end-of-dose fluctuations. No titration is
■ In this pilot study, the efficacy and tolerability of rasagiline, which has
already been demonstrated in large-scale clinical studies,1-3 was
■ At the final evaluation, over half (57%) of physicians rated the efficacy
Symptom severity (UPDRS-Motor scores)
assessed under everyday clinical practice conditions.
of rasagiline as ‘good/very good’.
In the assessment of symptom severity, there was a significant
■ Particular attention was focussed on data relating to PD-related sleep
improvement in UPDRS-Motor score from baseline (20.8 ± 7.7) to final
Safety and tolerability results
disturbances, and the occurrence of fatigue, which are key non-motor
evaluation (14.3 ± 8.7; p<0.001) – an improvement of 6.5 points over
■ A total of 24/26 patients (92%) experienced no ADRs, and no serious
adverse events were reported. Both patients who reported ADRs
withdrew from the study prematurely, but recovered following treatment
■ According to initial median PDSS scores, maintenance insomnia,
overall sleep quality, and sleep refreshment were the sleep-related
■ At the final evaluation, 79% of physicians rated the tolerability of
Patients and study design
symptoms that patients found most troubling at baseline (VAS scores
<4; Figure 1). Nocturnal psychosis and daytime dozing were least
■ This pilot study was conducted in seven centres (neurologists’
troubling at baseline (VAS scores >7).
practices) in Germany between September 2006 and December 2007.
■ As shown in Figure 2, from baseline to final evaluation, there were
■ Patients to be included in the study had idiopathic PD, and had been
marked improvements in the median PDSS total score (12%), and in
■ In this small-scale study set in routine clinical practice, PD patients
prescribed treatment with rasagiline (as monotherapy or as
the initially troubling individual PDSS items of maintenance insomnia
treated with rasagiline showed improved quality of sleep.
combination therapy with other anti-PD medications) by their treating
(200%), sleep refreshment (54%), and sleep quality (46%). Nocturnal
restlessness also showed notable improvement (29%).
■ Furthermore, fewer patients suffered from fatigue at the end of the
■ The observation and treatment period was approximately 8 weeks per
■ Other PDSS items, including nocturnal psychosis, showed no
patient, with study visits planned at baseline, ~4 weeks (interim visit)
worsening with rasagiline treatment.
■ This observational study supports the well-established safety and
Figure 1: Median PDSS scores, rated at baseline and final evaluation
Efficacy outcomes included the changes from baseline to final
evaluation in the measures listed below.
This study was supported by Teva Pharma GmbH and Lundbeck GmbH,
– Unified PD Rating Scale (UPDRS)-Motor score
Part III of the UPDRS, which measures the severity of a patient’s
motor symptoms based on 14 single items (symptoms).4 Each item is
1. Parkinson Study Group. A controlled trial of rasagiline in early Parkinson disease.
rated on a 5-point scale ranging from 0 (normal) to 4 (severe), and
The TEMPO study. Arch Neurol 2002; 59 (12): 1937–1943.
then totalled to give the UPDRS-Motor score.
2. Parkinson Study Group. A randomized placebo-controlled trial of rasagiline in
levodopa-treated patients with Parkinson disease and motor fluctuations. The
PRESTO study. Arch Neurol 2005; 62 (2): 241–248.
Visual analogue scale (VAS) used to assess sleep and nocturnal
3. Rascol O, Brooks DJ, Melamed E, et al, for the LARGO Study Group. Rasagiline
disability in PD.5 Patients rate the severities of 15 commonly reported
as an adjunct to levodopa in patients with Parkinson’s disease and motor
sleep-related symptoms, which are scored individually by marking a
fluctuations (LARGO, Lasting effect in Adjunct therapy with Rasagiline Given Once
cross along a 10 cm line that ranges from 0 (‘symptom severe and
daily, study): a randomised, double-blind, parallel-group trial. Lancet 2005; 365:
always experienced’) to 10 (‘symptom-free’). The maximum total
4. Fahn S, Elton R, members of the UPDRS Development Committee. Unified
Parkinson’s disease rating scale. In: Fahn S, et al (eds). Recent developments in
Parkinson’s disease. Volume II. Macmillan Health Care Information, Florham Park,
Self-rating scale designed to evaluate fatigue, and to differentiate it
6 Patients rate their agreement (on a scale
5. Chaudhuri KR, Pal S, DiMarco A, et al. The Parkinson’s disease sleep scale: a
from 1=no agreement, to 7=agreement) with nine statements
new instrument for assessing sleep and nocturnal disability in Parkinson’s disease.
J Neurol Neurosurg Psychiatry 2002; 73: 629–635.
concerning the severity, frequency and impact of fatigue on daily life.
6. Krupp LB, LaRocca NG, Muir-Nash J, Steinberg AD. The fatigue severity scale.
A mean statement/item score of ≥4 indicates that the patient is
Application to patients with multiple sclerosis and systemic lupus erythematosus.
Arch Neurol 1989; 46 (10): 1121–1123.
Poster presented at the 6th International Congress on Mental Dysfunctions & Other Non-Motor Features in Parkinson’s Disease, October 16–19, 2008; Dresden, Germany
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MALARIA AND HOMEOPATHIC REMEDIES IN GHANA An Open Study and a Double-Blind Randomized Clinical Trial V.M.A. van ERP 1 and M. BRANDS 2 1 BSc, Vrije Universiteit Amsterdam 2 MD, Homeopaths without Borders Netherlands 1. Introduction Malaria is a disease caused by four parasites: Plasmodium falciparum , P vivax , P. ovale and P. malariae . Each of them has its own morphological