Journal Reading Clinical Therapeutics/Volume 32, Number 14, 2010
Eleanor L. Olvey, PharmD; Edward P. Armstrong, PharmD; and Amy J. Grizzle, PharmD
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SMF Neurologi RSDM/FK UNS
Pengantar Metode Hasil
Level of Evidence Studi Pembanding
Pengukuran hasil
Tonus Otot dan Spasitisitas Kemampuan Fungsional dan Disabilitas Nyeri ROM (Range of Motion) Kualitas Hidup (yang berhubungan dgn kesehatran) Efek Samping
Diskusi Kesimpulan Critical appraisal
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MS : multiple sclerosis, CP : Cerebral Palsy, SSP :susunan saraf pusat, UMN : Upper Motor Neuron
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ASA : American Stroke Association
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AAN : american Academy of Neurology, BoNT : botulinum Neurotoxin, FDA US : Food and Drug Association United State, BTX : Botulinum toxin
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MEDLINE : Medical Literature Analysis and Retrieval System Online, EMBASE: excerpta Medica dataBASE, PRISMA :Preferred Reporting Items for Systemic Reviews anf meta-analysis
Table 1. criteria for levels of evidence, adapted frome the Oxford Centre for evidence-Based Medicine criteria
Evidence Level
Therapy/Prevention
1a
Systematic review of RCTs (with homogeneity)
1b
Individual RCT
2a
Systemic review of cohort studies (with homogeneity)
2b
Individual cohort study (including low quality randomized controlled open-label trials)
2c
Outcomes research studies
3a
Systemic review of case-control studies (with homogeneity)
3b
Individual case-control
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Case series (and poor-quality cohort and case-control studies)
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Expert opinion without explicit critical appraisal or based on physiology, bench research, or “firstprinciples” 8
262 penelitian di-Ekslusi Teridentifikasi 275 penelitian
Direview 113 penelitian
41 extremitas bawah 76 Duplikasi 52 etiologi Non-Stroke/diagnosis lain 22 komentar ahli/ediotrial 4 tidak berbahasa inggris 4 abstraksi 26 penelitian pediatri 4 penelitian cost effectiveness 2 meta-analyses 2 pooled analyses 8 systemic reviews
59 penelitian di-ekslusi karena tidak sesuai dengan kriteria inklusi dan ekslusi Total 54 penelitian 23 RCT 31 Open-label, non randomisasi, atau penelitian observasional Gambar 1 . Hasil dari strategi pengumpulan studi 9
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Table 2. sampel rangkuman penelitian Penulis/ deskripsi penelitian
Lo E
Regimen
Lokasi spastisitas
Outcome primer
Hasil
Bakheit et al (2000)39 DB, PC, dose ranging, 16 wk (N 83)
1b
injeksi BTX-A tunggal (abobotulinumtoxinA) 500, 1000, atau 1500 U atau Placebo
Bahu, pergelangan tangan
Spastisitas (MAS)
Penurunan yang signifikan dalam MAS ( setiap sendi ) di minggu 4 dengan semua BTX - A dosis vs plasebo ( 500 U : P 0,02 ; 1000 U : P 0,001 ; 1500 U : P 0,02 ) ; analisis besarnya manfaat ( perubahan MAS lebih dari 16 minggu ) ditemukan pengurangan MAS dengan semua BTX - A dosis di siku terpengaruh ( P 0.002 , P 0.006 , dan P 0,013 , masing-masing) dan pergelangan tangan ( P 0,028 , P 0,004 , dan P 0,017 ) , dan dengan BTX - A 1000 U di jari yang terkena dampak ( P 0,044 ) ; secara signifikan lebih banyak pasien dengan perbaikan di MAS di semua 3 sendi dengan BTX - A vs plasebo ( P 0,02 )
Hesse et al (1998)27 PC, 12 wk (N 24)
1b
injeksi BTX-A Tunggal (abobotulinumtoxinA) 1000 U, BTX-A 1000 U + strimulasi elektrik, placebo, or placebo +stimulasi elektrik
Siku, pergelangan tangan , jari tangan
Tonus otot (MAS)
Tidak ada perbedaan di antara kelompok MAS di siku , pergelangan tangan , atau jari pada setiap titik waktu
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Table 2. sampel rangkuman penelitian Penulis/ deskripsi penelitian
L o E
Marco et al (2007)25 DB, PC, 6 mo (N = 29)
1b
Injeksi tunggal BTX-A (abobotulinumtoxinA) 500 U or placebo; kedua kelompok mendapatkan TENS selama 6 minggu
Bahu
nyeri (VAS), spastisitas (MAS)
Penurunan yang signifikan dalam nyeri ( P 0,001 ) dan antara semua kelompok ( P 0,048 ) ; lebih besar penurunan rasa sakit dengan BTX - A vs plasebo ( P 0,035 ) ; tak ada perbedaan antara MAS kelompok pada setiap titik waktu
Simpson et al (1996)34 MC, DB, PC, PG, graduated dose, 16 wk (N=39)
1b
Injeksi tunggal BTX-A (onabotulinumtoxinA) (mean dose, 392 U)+ oral placebo, atau TZD (mean dose point, 20 mg/d) + injeksi placebo Injection, oral and Injeksi placebo
Siku, pergelanga n tangan , jari tangan, bahu
Perubahan dari baseline di pergelangan tangan fleksor nada di Titik akhir primer ( 6 minggu setelah inisiasi pengobatan) ( MAS )
Penurunan yang signifikan dalam MAS di mingu ke 6 dengan BTX - A vs TZD ( P 0,001 ) ; tidak ada perbedaan yang signifikan pada titik waktu dengan BTX - A vs plasebo
Regimen
Lokasi spastisitas
Outcome primer
Hasil
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Tonus Otot dan Spasitisitas
Kemampuan Fungsional dan Disabilitas
Functional Independence Measure (FIM), Fugl-Meyer scale, Barthel index atau Disability Assesment Scale (DAS)
Nyeri
Visual analog scale (VAS) 29 penelitian
Numeric pain rating scales (NRS) 13 penelitian
Fugl-Meyer scale 1 penelitian
DAS 4 penelitian
2 penelitian tidak menyebutkan skala pengukuran nyeri Secara keseseluruhan, terdapat hasil perbaikan nyeri yang tidak konsisten 13
ROM (Range of Motion)
Sebagian besar penelitian berfokus pada pasif ROM
26 penelitian perubahan ROM,abduksi/adduksi, fleksi/ekstensi
15 penelitian melaporkan adanya perbaikan signifikan ROM setelah pemberian terapi
Global Assesment
Dinilai berdasarkan bermacam instrumen yang meliputi pasien, keluarga pasien, dan dokter
Sebagian besar melaporkan adanya perbaikan spastisitas subjektif
Kualitas Hidup (yang berhubungan dgn kesehatan)
Terdapat hasil yang bervariasi
Efek Samping
Efek samping BTX-A yang paling sering terjadi : kelemahan lokal maupun general, nyeri di tempat injeksi dan fatigue
Efek samping BTX-B yang paling sering terjadi : mulut kering
Tidak ada efek samping yang serius maupun yang mengancam jiwa 14
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Design
• Systemic Review
Sample
• Pasien pasca stroke dengan spastisitas di extremitas superior
Time Place
• Penelitian yang Juli 2005 sampai januari 2010
• Multi Nasional 17
P
• Pasien pasca stroke dengan spastisitas di extremitas superior
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• BTX,TZD, ITB
C
• Antar penelitian
O
• • • • •
Tonus Otot dan Spasitisitas Kemampuan Fungsional dan Disabilitas Nyeri ROM (Range of Motion) Kualitas Hidup
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What question (PICO) did the systematic review address? What is best?
Where do I find the information?
The main question being addressed should be clearly stated. The exposure, such as a therapy or diagnostic test, and the outcome(s) of interest will often be expressed in terms of a simple relationship.
The Title, Abstract or final paragraph of the Introduction should clearly state the question. If you still cannot ascertain what the focused question is after reading these sections, search for another paper!
This paper: Yes Comment: Explained in Abstract and introduction
F - Is it unlikely that important, relevant studies were missed? What is best?
Where do I find the information?
The starting point for comprehensive search for all relevant studies is the major bibliographic databases (e.g., Medline, Cochrane, EMBASE, etc) but should also include a search of reference lists from relevant studies, and contact with experts, particularly to inquire about unpublished studies. The search should not be limited to English language only. The search strategy should include both MESH terms and text words. This paper: Unclear
The Methods section should describe the search strategy, including the terms used, in some detail. The Results section will outline the number of titles and abstracts reviewed, the number of full-text studies retrieved, and the number of studies excluded together with the reasons for exclusion. This information may be presented in a figure or flow chart.
Comment: This systematic review limited to english language only, and limited to the product BTX that administred in US Systematic Review appraisal Sheet (Oxford centre for evidence-based medicine)
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A - Were the criteria used to select articles for inclusion appropriate? What is best? The inclusion or exclusion of studies in a systematic review should be clearly defined a priori. The eligibility criteria used should specify the patients, interventions or exposures and outcomes of interest. In many cases the type of study design will also be a key component of the eligibility criteria.
Where do I find the information? The Methods section should describe in detail the inclusion and exclusion criteria. Normally, this will include the study design.
This paper: Yes Comment: Inclusion and exlusion criteria mentioned in methods, and there are key component to determine the criteria
A - Were the included studies sufficiently valid for the type of question asked? What is best? The article should describe how the quality of each study was assessed using predetermined quality criteria appropriate to the type of clinical question (e.g., randomization, blinding and completeness of follow-up)
Where do I find the information? The Methods section should describe the assessment of quality and the criteria used. The Results section should provide information on the quality of the individual studies.
This paper: Yes Comment:
Each study assesed by Level of Evidence based on Oxford centre for evidence-based criteria Systematic Review appraisal Sheet (Oxford centre for evidence-based medicine)
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T - Were the results similar from study to study? What is best?
Where do I find the information?
Ideally, the results of the different studies should be similar or homogeneous. If heterogeneity exists the authors may estimate whether the differences are significant (chi-square test). Possible reasons for the heterogeneity should be explored.
The Results section should state whether the results are heterogeneous and discuss possible reasons. The forest plot should show the results of the chi-square test for heterogeneity and if discuss reasons for heterogeneity, if present.
This paper: No Comment: The results is heterogenous. And there are no statistical analysis to determine the heterogenecity
What were the results? How are the results presented? presented as descriptive review, there are no statistical analysis
Systematic Review appraisal Sheet (Oxford centre for evidence-based medicine)
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