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P2.123 Ropinirole prolonged release improves nocturnal symptoms in patients with advanced Parkinson's disease: an analysis of grouped items on the PDSS
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Poster presentations / Parkinsonism and Related Disorders 15S2 (2009) S29–S199
mice fed the high n-3 PUFA diet compared to vehicle and MPTPtreated mice on the control diet (p < 0.05) and to vehicle mice on the high n-3 PUFA diet (p < 0.01). These results suggest that the modulation of BDNF expression contributes, in part, to n-3 PUFA-induced neuroprotection in a MPTP animal model of PD and strengthen the hypothesis that low levels of n-3 PUFA intake as a risk factor for PD. P2.120 iNOS-but not nNOS-inhibition protects against 6-OHDA-induced nigral cell loss in an animal model of PD M.J. Brzozowski1 , S. Lopez Alcantara2 , M.M. Iravani2 , S. Rose1 , P. Jenner1 . 1 NDRG, King’s College London, 2 Proximagen Ltd., London, UK Nitric oxide (NO) contributes to cell death in models of Parkinson’s disease (PD). However, the specific role of inducible (iNOS) or neuronal nitric oxide synthase (nNOS) remains uncertain. Therefore we have investigated the neuroprotective effect of iNOS and nNOS inhibitors on cell death in a 6-hydroxydopamine (6-OHDA) lesioned rat model of PD. Male Wistar rats were treated with the nNOS inhibitor, ARR17477 (6 mg/kg), or the iNOS inhibitor, 1400W (5 mg/kg), or saline 24 hours before and for 14 days after intrastriatal 6-OHDA injection (8 mg/4ml). Locomotor activity was assessed followed by immunohistochemical analysis of neuronal loss in substantia nigra (SN) and striatal dopamine and metabolite levels by HPLC analysis 28 days after surgery. There was no difference in locomotor activity between 6-OHDAlesioned rats treated with ARR17477 or 1400W compared to controls. 6-OHDA induced a 50–60% loss of dopamine, DOPAC and HVA in the striatum. ARR17477 and 1400W had no effect on the 6-OHDA-induced reduction in dopamine and its metabolites. 6-OHDA injection produced a 45% loss of tyrosine hydroxylase positive neurons in the SN. ARR17477 had no effect on 6-OHDAinduced cell loss, however, 1400W reduced the loss of dopaminergic neurons to 87% of control values (p < 0.01). These data suggest that inhibition of iNOS, but not nNOS reduces 6-OHDA-induced cell loss in rats. Interestingly iNOS inhibition reduced the loss of neurons in the SN, but not the loss of terminals in the striatum, suggesting a role for glial cells in nigral degeneration. P2.121 Enhancing safe mobility in patients with Parkinson’s disease: effect of dual task training during aerobic and moderate exercise N. Byl. Department of Physical Therapy and Rehab Science, University of California, San Francisco, Oakland, CA, USA Objective: Parkinson’s Disease (PD) can disturb mobility, attention, well being and quality of life. This study evaluated the effects of dual task learning based training activities during aerobic and moderate exercise in terms of mobility, falls and depression in patients with PD. Design: Small randomized single blinded clinical trial. Setting: Outpatient academic physical therapy site. Participants: Ten mentally alert, community independent patients with mild to moderate PD (Hoehn and Yahr stage 1–3) between 55 and 71 years. Intervention Learning based memory training (BrainfitPositscience) during moderate exercise (treadmill walking or cycling) and fine motor skill activities during aerobic exercise (body unweighted 30–50% with distributed airpressure – BWSTTDAPAlterg). Outcome variables: Timed gait (10 meter and six minute walk), strength (upper/lower limbs), balance (Berg Balance, Timed Get Up and Go, Five Times Sit to Stand), fine motor skills (Tapper and Digital Reaction Time), sensory discrimination (Graphesthesia) and depression (Beck Depression) were measured pre and immediately post exercise.
Data analysis: Dependent variables described, nonparametric tests applied to and effect sizes calculated. Results: Significant improvements (p ≤ 0.05) were measured on all dependent variables except upper extremity strength. The effect sizes ranged from 1.4 to 9.4 with a 96.7% decrease in falls (effect size −1.38), 28% decrease in depression (effect size −3.4) and 25% increase in endurance (effect size 4.7). Conclusions: Under condition of aerobic and moderate exercise, patients with mild to moderate PD can safely engage in dual task learning activities and significantly benefit in mobility, fall reduction and decreased depression. P2.122 PPAR-gamma agonist rosiglitazone stops the progressive dopaminergic degeneration induced by chronic MPTP in mice A. Carta, L. Frau. Toxicology, University of Cagliari, Cagliari, Italy Introduction: Modulation of neuroinflammatory responses by peroxisome proliferator-activated receptors-gamma (PPARg) represents a potential target for neuroprotective therapies in Parkinson’s disease (PD). Aim: The ability of PPARg agonist rosiglitazone to arrest ongoing dopaminergic degeneration and modulate neuroinflammatory responses was investigated in a mouse model of progressive PD. Design: C57Bl/6J mice received probenecid (250 mg/kg)/ MPTP (25 mg/kg) (MPTPp) twice weekly for 5 weeks. Daily delivery of rosiglitazone (10 mg/kg) was started to coincide with the 7th MPTPp injection, when about 15% of dopamine (DA) neurons were dyed, and continued until mice were sacrificed 3 days after MPTPp treatment. Dopaminergic degeneration in the SNc was evaluated by TH-immunoreactivity (ir) whereas CD11b-ir and GFAP-ir were evaluated to assess microglia and astroglia reactivity. Results: Mice receiving the full MPTPp treatment (10 injections) displayed a final 30% depletion of DA neurons in the SNc. In contrast, in rosiglitazone/MPTPp-treated mice, dopaminergic degeneration was about 15%, corresponding to levels found after 7 MPTPp injections, when rosiglitazone treatment was started. According results were observed in the neuroinflammatory response. MPTPp treatment induced a microglial and astroglial response characterized by a progressive increase of CD11b and GFAP-ir in the SNc. In rosiglitazone/MPTPp treated mice, glial response was arrested to levels found at the 7th MPTPp injection. Conclusion: Results indicate that rosiglitazone arrested neurodegenerative processes and inflammatory response ongoing during a chronic MPTPp treatment. Together with previous studies showing that rosiglitazone prevents onset of dopaminergic degeneration, results open new promising perspectives for treatment of PD. P2.123 Ropinirole prolonged release improves nocturnal symptoms in patients with advanced Parkinson’s disease: an analysis of grouped items on the PDSS K.R. Chaudhuri1 , K. Sethi2 , L. Giorgi3 , K. Rolfe4 , C.B. Rockett5 , N. Stover6 . 1 National Parkinson Foundation Centre of Excellence, Kings College Hospital, University Hospital Lewisham, Kings College and Institute of Psychiatry, London, UK; 2 Movement Disorders Clinic, Department of Neurology, Augusta, GA, USA; 3 GlaxoSmithKline, Greenford, 4 GlaxoSmithKline, Harlow, UK; 5 GlaxoSmithKline, Research Triangle Park, NC, 6 Department of Neurology, The University of Alabama at Birmingham, Birmingham, AL, USA Objective: To investigate the effect of ropinirole prolonged release on nocturnal symptoms in patients with advanced Parkinson’s disease (PD) not optimally controlled with L-dopa. Methods: Patients were randomized to placebo or adjunctive ropinirole prolonged release (2–24 mg/day; 24 weeks) (EASE-PD Adjunct [101468/169]). Nocturnal symptoms were assessed by PD Sleep Scale (PDSS) total score (range: 0–150; ≤100 = significant nocturnal symptoms). Post-hoc analyses included PDSS total and
Poster presentations / Parkinsonism and Related Disorders 15S2 (2009) S29–S199
grouped item scores: motor symptoms on waking (items 12, 13), global quality of sleep (GQS) (1, 2, 3, 14), dopamine-responsive symptoms (3, 4, 12, 13), nocturnal psychosis (6, 7), nocturnal restlessness (4) and daytime sleepiness (15). Results: Ropinirole prolonged release improved PDSS total score for patients with baseline PDSS ≤100 (adjusted mean treatment difference [AMTD] 9.0 [95% CI 2.76, 15.33] p = 0.0051), but not >100 (AMTD 1.7 [95% CI −3.25, 6.57] p = 0.5058). Treatment benefits over placebo for patients with baseline PDSS ≤100 were observed in the group analyses (all values mean[SD] change from baseline at Week 24 last observation carried forward): motor symptoms on waking (1.6[4.91] versus −0.1[4.95]); GQS (3.3[9.32] versus 0.7[8.79]); dopamine-responsive symptoms (3.1[8.07] versus 1.3[8.44]); nocturnal restlessness (1.0[3.52] versus 0.7[3.66]). No clinically relevant worsening of nocturnal psychosis or daytime sleepiness was observed with either treatment in patients with baseline PDSS ≤100. Conclusions: Ropinirole prolonged release improves nocturnal symptoms in patients with advanced PD who have significant nocturnal symptoms at baseline. Notable improvements are seen in GQS, dopamine-responsive symptoms and motor symptoms on waking, with no worsening of daytime sleepiness. Supported by GlaxoSmithKline R&D and SkyePharma. P2.124 Changes in quality of life and nocturnal symptoms in sleep-impaired patients with advanced Parkinson’s disease treated with ropinirole prolonged release P. Martinez-Martin1 , L. Giorgi2 , K. Rolfe3 , K.R. Chaudhuri4 . 1 Area of Applied Epidemiology, National Center for Epidemiology and CIBERNED, Carlos III Institute of Health, Madrid, Spain; 2 GlaxoSmithKline, Greenford, 3 GlaxoSmithKline, Harlow, 4 National Parkinson Foundation Centre of Excellence, Kings College Hospital, University Hospital Lewisham, Kings College and Institute of Psychiatry, London, UK Objective: To evaluate changes in health-related quality of life (HRQoL) and nocturnal symptoms in sleep-impaired patients with advanced Parkinson’s disease (PD) treated with ropinirole prolonged release. Methods: Patients were randomized to receive placebo or adjunctive ropinirole prolonged release (2–24 mg/day) (EASE-PD Adjunct study [101468/169]). HRQoL was evaluated using the PDQ-39 questionnaire and nocturnal symptoms were assessed with the PD Sleep Scale (PDSS) total score (range: 0–150; ≤100 = significant nocturnal symptoms). Change from baseline in PDQ-39 scores by baseline PDSS total score (≤100 or >100) were analysed post hoc. Results: In patients with PDSS score ≤100 at baseline, mean[SD] PDQ-39 scores improved (−4.17[11.80]) with ropinirole prolonged release and worsened (0.27[9.34]) in the placebo group at Week 24 last observation carried forward (LOCF), (decrease = improvement). Changes in PDSS total score in these patients were 10.2[24.6] for ropinirole prolonged release and 2.3[21.0] for placebo at Week 24 LOCF, with a significant adjusted mean treatment difference (AMTD) of 9.0, (95% CI 2.76, 15.33), p = 0.0051 (increase = improvement). In patients with baseline PDSS > 100, changes in PDQ-39 scores were (−1.83[8.59]) and (0.43[9.68]) at Week 24 LOCF for ropinirole prolonged release and placebo groups respectively. In this PDSS > 100 group, there was no significant treatment difference for PDSS total score at Week 24 LOCF (AMTD 1.7 [95% CI −3.25, 6.57], p = 0.5058). Conclusions: Ropinirole prolonged release improved HRQoL and significantly reduced nocturnal symptoms compared with placebo in patients with advanced PD not optimally controlled with L-dopa and who had significant nocturnal symptoms at baseline. Supported by GlaxoSmithKline R&D and SkyePharma.
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P2.125 Parkinson’s disease treatments in practice: evidence from the PD MED trial C. Clarke, S. Patel, V. Solanki, N. Ives, C. Rick, R. Gray, K. Wheatley. Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, UK Objective: To describe UK physician prescribing patterns of Parkinson’s disease (PD) treatments in the PD MED trial. Background: PD MED is a large, pragmatic, “real-life”, randomised trial to assess the cost-effectiveness of different drug classes for PD (www.pdmed.bham.ac.uk). Patients with early disease are randomised between open-label treatment with levodopa (LD), dopamine agonist (DA) or monoamine oxidase B inhibitor (MAOBI). Methods: Drug prescribing patterns were assessed using data from PD patients entered into early disease randomisation of PD MED. Results: By March 2009, 1471 early stage patients had been randomised. By 5 years, 48% of patients randomised to LD were receiving adjuvant therapy of DA, MAOBI and/or COMTI with LD. For those randomised to DA or MAOBI, by 5 years, 93% have either switched to another drug or had other drugs added to their treatment regimen. Prescribing patterns have changed during the trial. For those randomised to DA, ropinirole (61%) has been the preferred drug, however, since 2004 there has been an increase in pramipexole (34%) use. Most patients randomised to MAOBI were being prescribed oral selegiline (58%), though rasagiline (40%) use has increased in the last two years. There has been a steady decrease in sub-lingual selegiline (1%) use. Conclusion: By 5 years, around half of patients on LD are receiving adjuvant therapy and a large proportion of patients on DA and MAOBI have switched or had other drugs added. The trends in MAOBI use suggest that prescribing is heavily influenced by pharmaceutical company promotion rather than the evidencebase. P2.126 Follow-up study of patients with varying stage Parkinson’s disease in Hai, Tanzania, after 1 year of treatment with levodopa C. Dotchin1 , A. Jusabani2 , E. Aris3 , R. Walker4 . 1 Care of the Elderly, Institute for Ageing and Health, Newcastle upon Tyne, UK; 2 Radiology, Kilimanjaro Christian Medical Centre, Moshi, 3 Medicine, Muhimbili University, Dar es Salaam, Tanzania; 4 Medicine, North Tyneside General Hospital, North Shields, UK The Hai Parkinson’s disease (PD) project is a community-based prevalence study of PD. 33 patients were identified in 2005/6 [1]. Those surviving on 1st March 2007 were started on treatment with levodopa. The majority were drug naïve and had had symptoms for many years. It is not known whether introducing levodopa in late stage disease will be effective, or whether motor complications will develop more quickly than in early stage disease [2]. The aim of this study is to report the outcome for patients treated with levodopa in Hai 1 year after the introduction of medication. Of the 23 patients started on treatment, 19 (12 male) were alive at 1 year follow up, with mean age 77 years (range 41–96). Only 3 had been on medication for PD at the start of the study. Review by local PD nurse and assistant medical officers allows early recognition of problems, enforcement of compliance and ongoing supply of medication. 8/19 patients were experiencing wearing off of medication. None at this stage showed signs of dyskinesia. Mean UPDRS part III improved from 26 (pre-treatment 2006) to 25 (1 year post-treatment 2008), while median Hoehn and Yahr deteriorated slightly from 3.4 to 3.6. It is possible to identify, treat and follow up patients with PD in Tanzania. The introduction of levodopa has been effective and at 1 year no one had developed dyskinesias. We believe that this
Poster presentations / Parkinsonism and Related Disorders 15S2 (2009) S29–S199
mice fed the high n-3 PUFA diet compared to vehicle and MPTPtreated mice on the control diet (p < 0.05) and to vehicle mice on the high n-3 PUFA diet (p < 0.01). These results suggest that the modulation of BDNF expression contributes, in part, to n-3 PUFA-induced neuroprotection in a MPTP animal model of PD and strengthen the hypothesis that low levels of n-3 PUFA intake as a risk factor for PD. P2.120 iNOS-but not nNOS-inhibition protects against 6-OHDA-induced nigral cell loss in an animal model of PD M.J. Brzozowski1 , S. Lopez Alcantara2 , M.M. Iravani2 , S. Rose1 , P. Jenner1 . 1 NDRG, King’s College London, 2 Proximagen Ltd., London, UK Nitric oxide (NO) contributes to cell death in models of Parkinson’s disease (PD). However, the specific role of inducible (iNOS) or neuronal nitric oxide synthase (nNOS) remains uncertain. Therefore we have investigated the neuroprotective effect of iNOS and nNOS inhibitors on cell death in a 6-hydroxydopamine (6-OHDA) lesioned rat model of PD. Male Wistar rats were treated with the nNOS inhibitor, ARR17477 (6 mg/kg), or the iNOS inhibitor, 1400W (5 mg/kg), or saline 24 hours before and for 14 days after intrastriatal 6-OHDA injection (8 mg/4ml). Locomotor activity was assessed followed by immunohistochemical analysis of neuronal loss in substantia nigra (SN) and striatal dopamine and metabolite levels by HPLC analysis 28 days after surgery. There was no difference in locomotor activity between 6-OHDAlesioned rats treated with ARR17477 or 1400W compared to controls. 6-OHDA induced a 50–60% loss of dopamine, DOPAC and HVA in the striatum. ARR17477 and 1400W had no effect on the 6-OHDA-induced reduction in dopamine and its metabolites. 6-OHDA injection produced a 45% loss of tyrosine hydroxylase positive neurons in the SN. ARR17477 had no effect on 6-OHDAinduced cell loss, however, 1400W reduced the loss of dopaminergic neurons to 87% of control values (p < 0.01). These data suggest that inhibition of iNOS, but not nNOS reduces 6-OHDA-induced cell loss in rats. Interestingly iNOS inhibition reduced the loss of neurons in the SN, but not the loss of terminals in the striatum, suggesting a role for glial cells in nigral degeneration. P2.121 Enhancing safe mobility in patients with Parkinson’s disease: effect of dual task training during aerobic and moderate exercise N. Byl. Department of Physical Therapy and Rehab Science, University of California, San Francisco, Oakland, CA, USA Objective: Parkinson’s Disease (PD) can disturb mobility, attention, well being and quality of life. This study evaluated the effects of dual task learning based training activities during aerobic and moderate exercise in terms of mobility, falls and depression in patients with PD. Design: Small randomized single blinded clinical trial. Setting: Outpatient academic physical therapy site. Participants: Ten mentally alert, community independent patients with mild to moderate PD (Hoehn and Yahr stage 1–3) between 55 and 71 years. Intervention Learning based memory training (BrainfitPositscience) during moderate exercise (treadmill walking or cycling) and fine motor skill activities during aerobic exercise (body unweighted 30–50% with distributed airpressure – BWSTTDAPAlterg). Outcome variables: Timed gait (10 meter and six minute walk), strength (upper/lower limbs), balance (Berg Balance, Timed Get Up and Go, Five Times Sit to Stand), fine motor skills (Tapper and Digital Reaction Time), sensory discrimination (Graphesthesia) and depression (Beck Depression) were measured pre and immediately post exercise.
Data analysis: Dependent variables described, nonparametric tests applied to and effect sizes calculated. Results: Significant improvements (p ≤ 0.05) were measured on all dependent variables except upper extremity strength. The effect sizes ranged from 1.4 to 9.4 with a 96.7% decrease in falls (effect size −1.38), 28% decrease in depression (effect size −3.4) and 25% increase in endurance (effect size 4.7). Conclusions: Under condition of aerobic and moderate exercise, patients with mild to moderate PD can safely engage in dual task learning activities and significantly benefit in mobility, fall reduction and decreased depression. P2.122 PPAR-gamma agonist rosiglitazone stops the progressive dopaminergic degeneration induced by chronic MPTP in mice A. Carta, L. Frau. Toxicology, University of Cagliari, Cagliari, Italy Introduction: Modulation of neuroinflammatory responses by peroxisome proliferator-activated receptors-gamma (PPARg) represents a potential target for neuroprotective therapies in Parkinson’s disease (PD). Aim: The ability of PPARg agonist rosiglitazone to arrest ongoing dopaminergic degeneration and modulate neuroinflammatory responses was investigated in a mouse model of progressive PD. Design: C57Bl/6J mice received probenecid (250 mg/kg)/ MPTP (25 mg/kg) (MPTPp) twice weekly for 5 weeks. Daily delivery of rosiglitazone (10 mg/kg) was started to coincide with the 7th MPTPp injection, when about 15% of dopamine (DA) neurons were dyed, and continued until mice were sacrificed 3 days after MPTPp treatment. Dopaminergic degeneration in the SNc was evaluated by TH-immunoreactivity (ir) whereas CD11b-ir and GFAP-ir were evaluated to assess microglia and astroglia reactivity. Results: Mice receiving the full MPTPp treatment (10 injections) displayed a final 30% depletion of DA neurons in the SNc. In contrast, in rosiglitazone/MPTPp-treated mice, dopaminergic degeneration was about 15%, corresponding to levels found after 7 MPTPp injections, when rosiglitazone treatment was started. According results were observed in the neuroinflammatory response. MPTPp treatment induced a microglial and astroglial response characterized by a progressive increase of CD11b and GFAP-ir in the SNc. In rosiglitazone/MPTPp treated mice, glial response was arrested to levels found at the 7th MPTPp injection. Conclusion: Results indicate that rosiglitazone arrested neurodegenerative processes and inflammatory response ongoing during a chronic MPTPp treatment. Together with previous studies showing that rosiglitazone prevents onset of dopaminergic degeneration, results open new promising perspectives for treatment of PD. P2.123 Ropinirole prolonged release improves nocturnal symptoms in patients with advanced Parkinson’s disease: an analysis of grouped items on the PDSS K.R. Chaudhuri1 , K. Sethi2 , L. Giorgi3 , K. Rolfe4 , C.B. Rockett5 , N. Stover6 . 1 National Parkinson Foundation Centre of Excellence, Kings College Hospital, University Hospital Lewisham, Kings College and Institute of Psychiatry, London, UK; 2 Movement Disorders Clinic, Department of Neurology, Augusta, GA, USA; 3 GlaxoSmithKline, Greenford, 4 GlaxoSmithKline, Harlow, UK; 5 GlaxoSmithKline, Research Triangle Park, NC, 6 Department of Neurology, The University of Alabama at Birmingham, Birmingham, AL, USA Objective: To investigate the effect of ropinirole prolonged release on nocturnal symptoms in patients with advanced Parkinson’s disease (PD) not optimally controlled with L-dopa. Methods: Patients were randomized to placebo or adjunctive ropinirole prolonged release (2–24 mg/day; 24 weeks) (EASE-PD Adjunct [101468/169]). Nocturnal symptoms were assessed by PD Sleep Scale (PDSS) total score (range: 0–150; ≤100 = significant nocturnal symptoms). Post-hoc analyses included PDSS total and
Poster presentations / Parkinsonism and Related Disorders 15S2 (2009) S29–S199
grouped item scores: motor symptoms on waking (items 12, 13), global quality of sleep (GQS) (1, 2, 3, 14), dopamine-responsive symptoms (3, 4, 12, 13), nocturnal psychosis (6, 7), nocturnal restlessness (4) and daytime sleepiness (15). Results: Ropinirole prolonged release improved PDSS total score for patients with baseline PDSS ≤100 (adjusted mean treatment difference [AMTD] 9.0 [95% CI 2.76, 15.33] p = 0.0051), but not >100 (AMTD 1.7 [95% CI −3.25, 6.57] p = 0.5058). Treatment benefits over placebo for patients with baseline PDSS ≤100 were observed in the group analyses (all values mean[SD] change from baseline at Week 24 last observation carried forward): motor symptoms on waking (1.6[4.91] versus −0.1[4.95]); GQS (3.3[9.32] versus 0.7[8.79]); dopamine-responsive symptoms (3.1[8.07] versus 1.3[8.44]); nocturnal restlessness (1.0[3.52] versus 0.7[3.66]). No clinically relevant worsening of nocturnal psychosis or daytime sleepiness was observed with either treatment in patients with baseline PDSS ≤100. Conclusions: Ropinirole prolonged release improves nocturnal symptoms in patients with advanced PD who have significant nocturnal symptoms at baseline. Notable improvements are seen in GQS, dopamine-responsive symptoms and motor symptoms on waking, with no worsening of daytime sleepiness. Supported by GlaxoSmithKline R&D and SkyePharma. P2.124 Changes in quality of life and nocturnal symptoms in sleep-impaired patients with advanced Parkinson’s disease treated with ropinirole prolonged release P. Martinez-Martin1 , L. Giorgi2 , K. Rolfe3 , K.R. Chaudhuri4 . 1 Area of Applied Epidemiology, National Center for Epidemiology and CIBERNED, Carlos III Institute of Health, Madrid, Spain; 2 GlaxoSmithKline, Greenford, 3 GlaxoSmithKline, Harlow, 4 National Parkinson Foundation Centre of Excellence, Kings College Hospital, University Hospital Lewisham, Kings College and Institute of Psychiatry, London, UK Objective: To evaluate changes in health-related quality of life (HRQoL) and nocturnal symptoms in sleep-impaired patients with advanced Parkinson’s disease (PD) treated with ropinirole prolonged release. Methods: Patients were randomized to receive placebo or adjunctive ropinirole prolonged release (2–24 mg/day) (EASE-PD Adjunct study [101468/169]). HRQoL was evaluated using the PDQ-39 questionnaire and nocturnal symptoms were assessed with the PD Sleep Scale (PDSS) total score (range: 0–150; ≤100 = significant nocturnal symptoms). Change from baseline in PDQ-39 scores by baseline PDSS total score (≤100 or >100) were analysed post hoc. Results: In patients with PDSS score ≤100 at baseline, mean[SD] PDQ-39 scores improved (−4.17[11.80]) with ropinirole prolonged release and worsened (0.27[9.34]) in the placebo group at Week 24 last observation carried forward (LOCF), (decrease = improvement). Changes in PDSS total score in these patients were 10.2[24.6] for ropinirole prolonged release and 2.3[21.0] for placebo at Week 24 LOCF, with a significant adjusted mean treatment difference (AMTD) of 9.0, (95% CI 2.76, 15.33), p = 0.0051 (increase = improvement). In patients with baseline PDSS > 100, changes in PDQ-39 scores were (−1.83[8.59]) and (0.43[9.68]) at Week 24 LOCF for ropinirole prolonged release and placebo groups respectively. In this PDSS > 100 group, there was no significant treatment difference for PDSS total score at Week 24 LOCF (AMTD 1.7 [95% CI −3.25, 6.57], p = 0.5058). Conclusions: Ropinirole prolonged release improved HRQoL and significantly reduced nocturnal symptoms compared with placebo in patients with advanced PD not optimally controlled with L-dopa and who had significant nocturnal symptoms at baseline. Supported by GlaxoSmithKline R&D and SkyePharma.
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P2.125 Parkinson’s disease treatments in practice: evidence from the PD MED trial C. Clarke, S. Patel, V. Solanki, N. Ives, C. Rick, R. Gray, K. Wheatley. Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, UK Objective: To describe UK physician prescribing patterns of Parkinson’s disease (PD) treatments in the PD MED trial. Background: PD MED is a large, pragmatic, “real-life”, randomised trial to assess the cost-effectiveness of different drug classes for PD (www.pdmed.bham.ac.uk). Patients with early disease are randomised between open-label treatment with levodopa (LD), dopamine agonist (DA) or monoamine oxidase B inhibitor (MAOBI). Methods: Drug prescribing patterns were assessed using data from PD patients entered into early disease randomisation of PD MED. Results: By March 2009, 1471 early stage patients had been randomised. By 5 years, 48% of patients randomised to LD were receiving adjuvant therapy of DA, MAOBI and/or COMTI with LD. For those randomised to DA or MAOBI, by 5 years, 93% have either switched to another drug or had other drugs added to their treatment regimen. Prescribing patterns have changed during the trial. For those randomised to DA, ropinirole (61%) has been the preferred drug, however, since 2004 there has been an increase in pramipexole (34%) use. Most patients randomised to MAOBI were being prescribed oral selegiline (58%), though rasagiline (40%) use has increased in the last two years. There has been a steady decrease in sub-lingual selegiline (1%) use. Conclusion: By 5 years, around half of patients on LD are receiving adjuvant therapy and a large proportion of patients on DA and MAOBI have switched or had other drugs added. The trends in MAOBI use suggest that prescribing is heavily influenced by pharmaceutical company promotion rather than the evidencebase. P2.126 Follow-up study of patients with varying stage Parkinson’s disease in Hai, Tanzania, after 1 year of treatment with levodopa C. Dotchin1 , A. Jusabani2 , E. Aris3 , R. Walker4 . 1 Care of the Elderly, Institute for Ageing and Health, Newcastle upon Tyne, UK; 2 Radiology, Kilimanjaro Christian Medical Centre, Moshi, 3 Medicine, Muhimbili University, Dar es Salaam, Tanzania; 4 Medicine, North Tyneside General Hospital, North Shields, UK The Hai Parkinson’s disease (PD) project is a community-based prevalence study of PD. 33 patients were identified in 2005/6 [1]. Those surviving on 1st March 2007 were started on treatment with levodopa. The majority were drug naïve and had had symptoms for many years. It is not known whether introducing levodopa in late stage disease will be effective, or whether motor complications will develop more quickly than in early stage disease [2]. The aim of this study is to report the outcome for patients treated with levodopa in Hai 1 year after the introduction of medication. Of the 23 patients started on treatment, 19 (12 male) were alive at 1 year follow up, with mean age 77 years (range 41–96). Only 3 had been on medication for PD at the start of the study. Review by local PD nurse and assistant medical officers allows early recognition of problems, enforcement of compliance and ongoing supply of medication. 8/19 patients were experiencing wearing off of medication. None at this stage showed signs of dyskinesia. Mean UPDRS part III improved from 26 (pre-treatment 2006) to 25 (1 year post-treatment 2008), while median Hoehn and Yahr deteriorated slightly from 3.4 to 3.6. It is possible to identify, treat and follow up patients with PD in Tanzania. The introduction of levodopa has been effective and at 1 year no one had developed dyskinesias. We believe that this