Journal Reading. Clinical Therapeutics/Volume 32, Number 14, Eleanor L. Olvey, PharmD; Edward P. Armstrong, PharmD; and Amy J.

Clinical Therapeutics/Volume 32, Number 14, 2010

Eleanor L. Olvey, PharmD; Edward P. Armstrong, PharmD; and Amy J. Grizzle, PharmD

Journal Reading

1 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

3 MS : multiple sclerosis, CP : Cerebral Palsy, SSP :susunan saraf pusat, UMN : Upper Motor Neuron

5 AAN : american Academy of Neurology, BoNT : botulinum Neurotoxin, FDA US : Food and Drug Association United State, BTX : Botulinum toxin

7 MEDLINE : Medical Literature Analysis and Retrieval System Online, EMBASE: excerpta Medica dataBASE, PRISMA :Preferred Reporting Items for Systemic Reviews anf meta-analysis

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

4 Case series (and poor-quality cohort and case-control studies)

5 Expert opinion without explicit critical appraisal or based on physiology, bench research, or “first-principles”

9

Teridentifikasi

275

penelitian

262

penelitian di-Ekslusi 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

Direview

113

penelitian

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

11

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

Table 2. sampel rangkuman penelitian Penulis/ deskripsi penelitian L o E Regimen Lokasi

spastisitas Outcome primer Hasil

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



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



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

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• Systemic Review

Design

• Pasien pasca stroke dengan spastisitas di extremitas

superior

Sample

• Penelitian yang Juli 2005 sampai januari 2010

Time

• Multi Nasional

• Pasien pasca stroke dengan spastisitas di extremitas superior

P

• BTX,TZD, ITB

I

• Antar penelitian

C

• Tonus Otot dan Spasitisitas

• Kemampuan Fungsional dan Disabilitas

• Nyeri

• ROM (Range of Motion)

• Kualitas Hidup

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.

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.

This paper: Unclear Comment:

This systematic review limited to english language only, and limited to the product BTX that administred in US

19 Systematic Review appraisal Sheet (Oxford centre for evidence-based medicine)

A - Were the criteria used to select articles for inclusion appropriate?

What is best? Where do I find the information?

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.

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? Where do I find the information?

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)

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:

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

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How are the results presented?

presented as descriptive review, there are no statistical analysis

What were the results?