Transcript Case presentation

神經內科
實證期刊閱讀報告
EBM-style Journal Reading
報告人：梁均瑜
指導臨床教師：陳彥宇醫師
日期：2015-02-11
地點：83病房討論室
Ask
Foreground question

Are corticosteroids more effective then placebo for improving
vestibular function and relieving symptoms such as vertigo in
patients with vestibular neuritis?
Clinical Uncertainty → PICO 問題
臨床個案的PICO
Patient / Problem
Patients with vestibular neuritis
Intervention
Croticosteroids
Comparison
Placebo
Outcome
Vestibular function;
Symptomatic improvement (vertigo)
Type of Question: Therapy
Acquire
UpToDate
DynaMed
ACP PIER
BMJ Clinical Evidence
ACP journal club
Evidencebasedmedicine.com
Cochrane Library
BMJ Evidence Updates
Other Systemic reviews
ex: PubMed systemic reivew
PubMed
SUMsearch
TRIP
Google
systems
Computerized
decision support
summaries
Evidence based
textbooks
synopses
Evidence based
journal abstract
syntheses
Systemic reviews
studies
Original journal
articles
搜尋Summaries (UpToDate)
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資料庫： UpToDate
搜尋日期：2015-02-09
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搜尋關鍵字與策略：Vestibular neuritis

Best available evidence:
（挑選可獲得之最佳研究證據）

Citation/s:
Vestibular neuritis and labyrinthitis
UpToDate Literature review current through: Jan 2015.|
This topic last updated: Aug 09, 2013.

Lead author's name :
Joseph M Furman, MD, PhD
經由UpToDate的reference ，
找到Cochrane library的一篇 systemic review
Best available evidence:
（挑選可獲得之最佳研究證據）

Citation/s:
Corticosteroids for the treatment of idiopathic acute
vestibular dysfunction (vestibular neuritis).
Cochrane Database Syst Rev. 2011 May 11

Lead author's name :
Jonathan M Fishman
Methods-1

Types of studies: Randomized controlled trials

Types of participants:
◦ Inclusion criteria
 Adults(> 16 y/o) of either gender, diagnosed with vestibular neuritis
(idiopathic acute peripheral vestibular dysfunction/ vestibulopathy,
rather than acute cochleo-vestibular dysfunction),
as defined by the following criteria:
 First episode of sudden onset sustained vertigo measured in days
 Absence of auditory symptoms or findings suggestive of alternative diagnoses
 Absence of neurological signs other than spontaneous nystagmus (unidirectional,
horizontal, obeying Alexander’s Law and enhancing with removal of optic fixation),
a positive head-thrust test or a positive Romberg’s test
 Absence of neurological symptoms or findings suggestive of alternative diagnoses
Treatment must be initiated within seven days of the onset of symptoms.
◦ Exclusion criteria
 Exclude patients with any other cause of acute vertigo
(e.g. Benign paroxysmal positional vertigo, Ménière’s disease)
Methods-2

Types of interventions
◦ Any corticosteroids (any timing, any dose, by oral/intravenous/intramuscular/
intratympanic route and of any duration), including medications such as prednisolone,
dexamethasone, methylprednisolone, etc.
◦ Corticosteroids were compared to placebo, no treatment, any active intervention and/or
any active comparator.

Types of outcome measures
◦ Primary outcomes
 Proportion of patients that recover
 Degree of recovery (if appropriate) of peripheral vestibular function in patients with
idiopathic acute vestibular dysfunction, through subjective patient reporting of
symptoms, use of validated questionnaires, or objective evidence of recovery (e.g.
electronystagmography, caloric testing and other vestibular function and balance tests),
as defined by the authors.
◦ Secondary outcomes
 Time to recovery, including a return to normal activities and health-related quality of life
measures (generic, or disease specific, or both).
 Patient-reported adverse events: severe and minor.
 A severe adverse event is defined as resulting in a patient discontinuing the medication and
withdrawing from the study. A minor adverse event is defined as a side effect experienced by the
patient but where they continue to take the medication.
Methods-3

Search methods for identification of studies
◦ Systematic searches for randomized controlled trials. There were no language,
publication year or publication status restrictions. We contacted original authors for
clarification and further data if trial reports were unclear.
The date of the most recent search was 28 December 2010.
◦ Electronic searches
 We identified published, unpublished and ongoing studies by searching the following
databases from their inception: the Cochrane Ear, Nose and Throat Disorders Group
Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL) (The
Cochrane Library 2010, Issue 4); PubMed; EMBASE; CINAHL; LILACS; KoreaMed;
IndMed; PakMediNet; CAB Abstracts; Web of Science; BIOSIS Previews; CNKI;
mRCT; ClinicalTrials.gov; ICTRP and Google.
◦ Searching other resources
 We scanned reference lists of identified publications for additional trials and contacted
authors as necessary.
Methods-4
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Data collection and analysis
◦ Selection of studies  Two authors (JMF and CB)
◦ Data extraction and management  Two authors (JMF and CB)
◦ Assessment of risk of bias in included studies
◦ Measures of treatment effect
 Risk ratio (RR) with 95% confidence intervals (CI)
 Mean differences (MD) and standardized mean differences (SMD) with 95% CI
◦ Dealing with missing data  intention-to-treat basis
◦ Assessment of heterogeneity  Chi2 test and I2 statistic available in RevMan 5.1
◦ Assessment of reporting biases
◦ Data synthesis  Review Manager 5.1
◦ Subgroup analysis and investigation of heterogeneity
◦ Sensitivity analysis  NOT appropriate if the number of included trials is low
本篇文獻的PICO(T)
Patient / Problem Patients with vestibular neuritis
Intervention
Croticosteroids
Comparison
Placebo
Outcome
Complete caloric recovery;
The extent of caloric recovery;
Symptomatic recovery of vestibular function (vertigo);
Dizziness Handicap Inventory score
Time
24 hrs, one, three, six and 12 months
Results-1
RCT
Total
(corticosteroids/placebo)
20 (10/10)
32 mg methylprednisolone/PO
on the first day and then decreased to
4 mg gradually
over the next seven days
40 (20/20)
18 mg dexamethasone daily/PO
(6 mg TID/PO) for three days +
100 mg dimenhydrinate daily for three
days/ Placebo + dimenhydrinate
30 (15/15)
Prednisolone 1 mg/kg daily/PO
for five days, followed by reducing
regimen for the next 15 days +
Famotidine 20 mg daily
73 (35/38)  59 (29/30)
100 mg methylprednisolone QD/PO,
for three days, then tapered off to
10 mg over the next 19 days
Ariyasu
1990
Rezaie
2006
Shupak
2008
Strupp
2004
149 (74/75)
Results-2
Moderate, Grade B
Moderate,
Grade B
High, Grade C
Moderate, Grade B
Results-3
Cochrane Database Syst Rev. 2011 May 11
Otol Neurotol. 2010 Feb;31(2):183-9.
Results-4
Cochrane Database Syst Rev. 2011 May 11
因使用fixed-effect model，而使統計上有顯著差異；但I2 =79% >50%，
有significant heterogeneity，應使用random-effects model分析，
若改用random-effects model分析，就沒有統計上的顯著差異了。
Otol Neurotol. 2010 Feb;31(2):183-9.
Results-5
Results-6
Results-7
Results-8
Results-9
Results-10
Results-11
Although the results were significant,
the risk of bias is high (Grade C for overall methodological quality)
and the patient numbers small.
Conclusions

Based on the currently available data,
there is insufficient evidence to support the use of
corticosteroids in the management of patients with
idiopathic acute vestibular dysfunction(vestibular neuritis).
搜尋Studies (PubMed)
搜尋前面Cochrane library那篇(2011)之後的文章
(設定5年內)

資料庫： PubMed
搜尋日期：2015-02-09

搜尋關鍵字與策略：

◦ (("Steroids"[Mesh]) OR "Glucocorticoids"[Mesh]) AND "Vestibular
Neuronitis/therapy"[Mesh]
在前面Cochrane library那篇(2011)之後，並沒有RCT比較
corticosteroids和placebo對vestibular neuritis的效果。
Appraise
Grade down due to small sample size
and moderate to high risk of bias
Apply



綜合上述，現在並沒有很強烈的建議corticosteroids用在
vestibular neuritis 的病人身上。雖然在某些trial顯示
cortisteroids可改善短期的vestibular function，但長期來講並沒
有統計上的顯著差異；且早期的研究也顯示caloric recovery和
recovery of clinical symptoms並沒有相關。此外，前面提到的4
個clinical trials，其sample size都太小且也都存在一些bias。
 但UpToDate的作者還是建議corticosteroids的治療
病人沒有peptic ulcer 的history
病人在急診打了1支 chlorpheniramine和3支NaHCO3後，症狀
完全沒改善。與病人及家屬詳細討論後，病人願意嘗試
corticosteroids的治療。
 治療隔天，症狀大有改善
Clinical
Expertise
Best Research
Evidence
Patient
Preferences
回到臨床個案情境
Clinical bottom line 臨床決策底線
Overall, there is insufficient evidence from these
trials to support the administration of corticosteroids
to patients with idiopathic acute vestibular
dysfunction (vestibular neuritis).
 使用類固醇與否，應考慮其可能的副作用，也應詳細
的與病人及家屬討論。

References:
1.
Fishman JM1, Burgess C, Waddell A. Corticosteroids for the treatment of
idiopathic acute vestibular dysfunction (vestibular neuritis). Cochrane
Database Syst Rev 2011;5:CD008607.
2.
Goudakos JK1, Markou KD, Franco-Vidal V, Vital V, Tsaligopoulos M,
Darrouzet V. Corticosteroids in the treatment of vestibular neuritis: a
systematic review and meta-analysis. Otol Neurotol 2010;31:183-9.
3.
Strupp M, Zingler VC, Arbusow V, et al. Methylprednisolone, valacyclovir,
or the combination for vestibular neuritis. N Engl J Med 2004;351:354-61.
4.
Shupak A, Issa A, Golz A, et al. Prednisone treatment for vestibular
neuritis. Otol Neurotol 2008;29:368-74.
結 論
（臨床底線的精要敘述）
There is insufficient evidence from these trials to support the
administration of corticosteroids to patients with idiopathic
acute vestibular dysfunction (vestibular neuritis).
Kill or Update By（下次更新日期）:
2016年 02月 11日
Audit
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我提出的問題是否具有臨床重要性？yes
我是否明確的陳述了我的問題？ yes
我的foreground question 是否可以清楚的寫成PICO？yes
我是否清楚的知道自己問題的定位？（亦即可以定位自己
的問題是屬於診斷上的、治療上的、預後上的或流行病學
上的），並據以提出問題？yes
對於無法立刻回答的問題，我是否有任何方式將問題紀錄
起來以備將來有空時再找答案？yes
我是否將搜尋到的最佳證據應用到我的臨床工作中？yes
我是否因此搜尋結果而改變了原來的治療策略？做了那些
改變？Yes
這篇報告，我總共花了多少時間？14hr
我是否覺得這個進行實證醫學的過程是值得的？yes