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Prof. Dr.
Soebandrio SpPD KEMD
Prof DR dr R Dkokomeoljanto SpPD-KEMD teot McElveen. 2012. NPH. Diakses dari: http://emedicine.medscape.com/article/1143066- overview. 8. Djuanda, A dkk. Ilmu Penyakit Kulit dan kelamin : Penyakit Virus. Jakarta: Fakultas Kedokteran Universitas Indonesia. 1993; (3): 94-95 9. Bowsher D. The lifetime occurence of herpes zoster and prevalence of post-herpetic neuralgia: a retrospective survey in an elderly population. Eur J Pain 1999;3:335-42 10. Dworkin RH, Portenoy RK. Proposed classification of herpes zoster pain. Lancet 1994;343:1648. Robert Zorba Paster, The Challenges of in the Long-Term Care Setting Postherpetic Neuralgia. Endo Pharmaceuticals. 2011;1:1. 12. Mario Roxas, ND. 2006. Herpes Zoster and NPH: Diagnosis and Therapeutic Considerations. Alternative Medicine Review. 2006; 11:2 13. Jericho Barbara G. Postherpetic Neuralgia: A Review. The Internet Journal of Orthopedic Surgery. 2010;16: 2. 14. Gharibo Christopher, Kim Carolyn. Neuropatic Pain of Postherpetic Neuralgia. Pain Medicine News Special Edition. 2010 15. Hopper AH, Brown RH. Adams and Victors Principles of Neurology. 7th ed. New York, NY: McGraw Hill; 2005:797 16. Meliala L. Patofisiologi Nyeri. Nyeri Neuropatik. Kelompok studi nyeri PERDOSSI 2008 ; 1-28 17. Meliala L. NPH. Penuntun Penatalaksaan Nyeri Neuropatik. Kelompok studi nyeri PERDOSSI 2007 ; 59-60
Kdiuff Priruhfjfn http://www.youtube.com/watch?v=Vzs4_-gYNwk hcjdjjdjdj Prof Dr dr Suhartono SpPS Betsoy scrotum crott
1484
May 18, 2000 The New England Journal of Medicine A FIVE-YEAR STUDY OF THE INCIDENCE OF DYSKINESIA IN PATIENTS WITH EARLY PARKINSONS DISEASE WHO WERE TREATED WITH ROPINIROLE OR LEVODOPA O LIVIER R ASCOL , M.D., P H .D., D AVID J. B ROOKS , M.D., D.S C ., A MOS D. K ORCZYN , M.D., P ETER P. D E D EYN , M.D., P H .D., C ARL E. C LARKE , M.D., AND A NTHONY E. L ANG , M.D., FOR THE 056 S TUDY G ROUP * A BSTRACT Background There is debate about whether the initial treatment for patients with Parkinsons disease should be levodopa or a dopamine agonist. Methods In this prospective, randomized, double- blind study, we compared the safety and efficacy of the dopamine D2receptor agonist ropinirole with that of levodopa over a period of five years in 268 pa- tients with early Parkinsons disease. If symptoms were not adequately controlled by the assigned study medication, patients could receive supplementary levodopa, administered in an open-label fashion. The primary outcome measure was the occurrence of dyskinesia. Results Eighty-five of the 179 patients in the ro- pinirole group (47 percent) and 45 of the 89 patients in the levodopa group (51 percent) completed all five years of the study. In the ropinirole group, 29 of the 85 patients (34 percent) received no levodopa supplementation. The analysis of the time to dyski- nesia showed a significant difference in favor of ro- pinirole (hazard ratio for remaining free of dyskine- sia, 2.82; 95 percent confidence interval, 1.78 to 4.44; P<0.001). At five years, the cumulative incidence of dyskinesia (excluding the three patients who had dyskinesia at base line), regardless of levodopa sup- plementation, was 20 percent (36 of 177 patients) in the ropinirole group and 45 percent (40 of 88 pa- tients) in the levodopa group. There was no signifi- cant difference between the two groups in the mean change in scores for activities of daily living among those who completed the study. Adverse events led to the early withdrawal from the study of 48 of 179 patients in the ropinirole group (27 percent) and 29 of 89 patients in the levodopa group (33 percent). The mean (SD) daily doses given by the end of the study were 16.56.6 mg of ropinirole (plus 427221 mg of levodopa in patients who received supple- mentation) and 753398 mg of levodopa (including supplements). Conclusions Early Parkinsons disease can be man- aged successfully for up to five years with a reduced risk of dyskinesia by initiating treatment with ropini- role alone and supplementing it with levodopa if nec- essary. (N Engl J Med 2000;342:1484-91.) 2000, Massachusetts Medical Society. From the Clinical Investigation Center, Neuropharmacology Unit, INSERM Unit 455, University Hospital, Toulouse, France (O.R.); the Division of Neuroscience, Imperial College School of Medicine, Hammer- smith Hospital, London (D.J.B.); the Department of Neurology, Tel Aviv University Medical School, Ramat Aviv, Israel (A.D.K.); the Department of Neurology, General Hospital Middelheim, Born-Bunge Foundation, and University of Antwerp, Antwerp, Belgium (P.P.D.); the Department of Neurology, University of Birmingham, Birmingham, United Kingdom (C.E.C.); and the Department of Medicine (Neurology), University of To- ronto and Toronto Western Hospital, Toronto (A.E.L.). Address reprint re- quests to Dr. Rascol at the Service de Pharmacologie Medicale et Clinique, Facult de Mdecine, 37 Alles Jules-Guesde, 31073 Toulouse CEDEX, France, or at [email protected]. *The investigators who participated in the study are listed in the Appendix. LTHOUGH the antiparkinsonian effect of the dopamine precursor levodopa was first demonstrated 30 years ago, 1 and that of dopamine D2receptor agonists more than 25 years ago, 2 the most appropriate time to begin these two treatments in patients with Parkinsons dis- ease remains controversial. 3 Some neurologists pro- mote the early use of levodopa, emphasizing the rapid symptomatic benefit 4 and the possible reduction in mortality that the drug provides. 5 Others, more con- cerned about the potential neurotoxicity 6 and the long-term complications, such as dyskinesia, associ- ated with the use of levodopa, 7-11 encourage the ear- ly use of dopamine agonists. This long-standing con- troversy remains largely unresolved, 12 although recent data suggest that initiating treatment with a dopa- mine agonist confers some advantage. 13,14 Data from studies of monkeys treated with 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine have demonstrated that dopamine agonists are less likely than levodopa to induce dyskinesia in animals that have not been ex- posed to levodopa. 15 Because dyskinesia is one of the most debilitating effects of levodopa therapy, we stud- ied the incidence of dyskinesia associated with the two treatments in a large, prospective, randomized, five-year study. Ropinirole is a nonergot-derived D2-like dopa- mine-receptor agonist that is effective in the treat- ment of early 14,16,17 and late 18,19 Parkinsons disease. The effectiveness of ropinirole in the treatment of ear- ly Parkinsons disease has already been demonstrated through a planned interim analysis of the data from the study described here, conducted six months after the study was begun, in which the primary end point was the score for motor function on the Unified Par- kinsons Disease Rating Scale (UPDRS). 17 We present here the results of the final five-year analysis, in which A The New England Journal of Medicine Downloaded from nejm.org at THUERINGER UNIVERSITAETS-UND on November 19, 2012. For personal use only. No other uses without permission. Copyright 2000 Massachusetts Medical Society. All rights reserved. INCIDENCE OF DYSKINESIA AFTER ROPINIROLE OR LEVODOPA IN PATIENTS WITH EARLY PARKINSONS DISEASE Volume 342 Number 20
1485 the primary outcome measure was the incidence of dyskinesia. METHODS Study Population A total of 268 patients were enrolled at 30 centers (in Europe, Israel, and Canada). All patients were 30 years of age or older, had a clinical diagnosis of Parkinsons disease 20 with a Hoehn Yahr rating of stage 1 through 3 (with stage 1 indicating unilat- eral, early disease and stage 3 more advanced, bilateral disease), 21 and required dopaminergic therapy. Prior short-term treatment with levodopa or dopamine agonists was limited to a maximum of six weeks and had to be discontinued at least two weeks before entry into the study. Patients were excluded if they had severe dizziness or fainting, severe systemic disease, major psychosis, severe dementia, alco- holism or drug dependence, or a contraindication to levodopa. In addition, treatment with a monoamine oxidase inhibitor within two weeks before entry (with the exception of selegiline) or pre- vious treatment with ropinirole were reasons for exclusion. Study Design This prospective, randomized, double-blind study was designed to compare the risk of dyskinesia in early Parkinsons disease among patients treated with ropinirole (Requip, SmithKline Beecham, Philadelphia) with that among patients treated with a combina- tion of levodopa and benserazide (Madopa, HoffmannLaRoche, Nutley, N.J.; referred to hereafter as levodopa) over a period of five years. Random treatment assignment was performed with a ropinirole-to-levodopa ratio of 2:1. Benserazide has been shown previously to have properties that are similar to those of carbidopa (used with levodopa in Sinemet [Dupont Merck, Wilmington, Del.]) in blocking dopa decarboxylase in the periphery. 22,23 Blind- ing of the study was maintained with the use of a double-dummy technique. Sealed copies of the randomization code were held by the principal investigator at each site and by the study sponsor. Patients underwent a single-blind placebo run-in period lasting seven days to demonstrate at least 80 percent compliance with taking study medication. Patients were then randomized (with stratification according to whether they were receiving concomi- tant selegiline therapy), and assessments were performed at week- ly intervals for the first month, every two weeks for the next two months, every month up to six months, and every two months thereafter. The study was conducted in accordance with Good Clinical Practices guidelines and the Declaration of Helsinki. The proto- col was approved by an ethics committee at each center, and writ- ten informed consent was obtained from each patient. Treatment Both ropinirole and levodopa were taken orally in tablet form. The dose of study medication was adjusted weekly as required, with 13 possible increasing dose levels. Ropinirole therapy was initiated (dose level 1) at 0.75 mg per day (0.25 mg three times daily) and levodopa therapy at 50 mg once daily plus placebo twice daily. The maximal daily doses of study medication allowed (dose level 13) were 24 mg of ropinirole per day (8 mg three times daily) and 1200 mg of levodopa per day (400 mg three times daily). Investigators were encouraged to treat patients only with the assigned study medication. Patients whose symptoms were not adequately controlled by the adjustment of study medication alone (i.e., those with recurrent, persistent, or functional disabili- ty), despite use of the highest tolerated dose, could be given sup- plementary levodopa in open-label fashion. No other antiparkin- sonian therapies were permitted after the start of the study. Domperidone was permitted according to the normal practice at each individual study center, to control severe dizziness, nausea, or vomiting. Clinical Assessments Dyskinesia Dyskinesia (the incidence of which was assessed in patients be- fore withdrawal from the study or until completion of the study) was considered to be present if a patient had a score of 1 or more (on a scale from 0 to 4, where a score of 0 indicates no dyskinesia and a score of 4 indicates dyskinesia during most waking hours) on item 32 of the UPDRS 24 (Duration: what proportion of the waking day are dyskinesias present?) or if dyskinesia was report- ed as an adverse event. In addition, all reports of adverse events consisting of abnormal movements considered to be dyskinesia were reviewed before the randomization code was broken. Additional Variables Disabling dyskinesia was defined as a score of 1 or more on items 32 and 33 of the UPDRS (How disabling are the dyski- nesias?). The scores for activities of daily living and motor function were measured with the use of parts II and III of the UPDRS (items 5 through 17 [range of possible scores, 0 to 52, where 0 indicates no disability and 52 indicates maximal impairment] and items 18 through 31 [range of possible scores, 0 to 108, where 0 indicates no disability and 108 indicates maximal impairment]), respective- ly, for the patients who completed the study. Wearing off (defined as periods of increased severity of par- kinsonian symptoms as medication wears off ) was assessed by re- viewing the data from patients who reported increases in the du- ration of time awake and in an off period on item 39 of the UPDRS. Freezing when walking was assessed by reviewing re- sponses to item 14 of the UPDRS. Safety and Tolerability of the Drugs Adverse events were assessed in a standard manner by the in- vestigator. Neuropsychiatric adverse events (i.e., hallucinations, con- fusion, d elirium, psychosis, illusion, delusion, depersonalization, personality disorder, abnormal thinking, amnesia, dementia, im- paired concentration, and other related events, as defined by the World Health Organization) were the only predetermined meas- ures of safety in the statistical analyses. Statistical Analysis We planned to enroll 240 patients into the study (160 randomly assigned to ropinirole and 80 to levodopa); this number was cal- culated on the assumption of an underlying rate of response to treatment of 85 percent. Samples of 110 patients in the ropinirole group and 55 in the levodopa group who could be evaluated at the six-month interim analysis 17 provided the study with an 80 percent chance of demonstrating equivalent efficacy in the two groups (with a 90 percent confidence interval), on the assumption that the response rate in the levodopa group would not be more than 15 percent higher than that in the ropinirole group. It was anticipated that 30 patients in the ropinirole group and 50 in the levodopa group would complete all five years (predicted withdrawal rates, 30 percent and 10 percent per year, respectively). These numbers of patients provided the study with 88 percent power to detect a dif- ference (P<0.05) in the incidence of dyskinesia between the two groups, assuming an incidence of 5 percent in the ropinirole group and an incidence of 30 percent in the levodopa group. All analyses (except those based on the scores for activities of daily living and motor function) were performed on an intention- to-treat basis and include all randomized patients who had at least one assessment after receiving study medication. Patients were not followed up for assessment of dyskinesia after withdrawal from the study. The rates of dyskinesia and disabling dyskinesia in the two groups were compared with the use of the Cox proportional-haz- ards model 25 in an analysis of failure time (time to an episode of dyskinesia or disabling dyskinesia). KaplanMeier curves, 26 haz- The New England Journal of Medicine Downloaded from nejm.org at THUERINGER UNIVERSITAETS-UND on November 19, 2012. For personal use only. No other uses without permission. Copyright 2000 Massachusetts Medical Society. All rights reserved.