NEJM Audio Summary - March 22, 2012

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5:47| "A Randomized Trial of Tenecteplase versus Alteplase for Acute Ischemic Stroke" by Mark Parsons, from the University of Newcastle, Australia.
This phase 2B trial, using CT perfusion and angiographic imaging to select patients for thrombolytic treatment of acute ischemic stroke, compared the standard dose of alteplase with two different doses of tenecteplase. The three treatment groups each comprised 25 patients. The mean National Institute of Health Stroke Scale score at baseline for all patients was 14.4, and the time to treatment was 2.9. Together, the two tenecteplase groups had greater reperfusion and clinical improvement at 24 hours than the alteplase group. There were no significant between-group differences in intracranial bleeding or other serious adverse events. The higher dose of tenecteplase (0.25 mg per kilogram) was superior to the lower dose and to alteplase for all efficacy outcomes, including absence of serious disability at 90 days (in 72% of patients, vs. 40% with alteplase. Tenecteplase was associated with significantly better reperfusion and clinical outcomes than alteplase in patients with stroke who were selected on the basis of CT perfusion imaging. 

詳細は、下畑享良先生のブログ"Neurology 興味を持った「神経内科」論文"の記事「脳梗塞に対する血栓溶解薬テネクテプラーゼはアルテプラーゼより優れているようだ」を参照。

NEJM Audio Summary - March 15, 2012

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0'47"| "Prostate-Cancer Mortality at 11 Years of Follow-up" by  Fritz Schröder from Erasmus University Medical Center, Rotterdam in the Netherlands.
The authors updated prostate-cancer mortality in the European Randomized Study of Screening for Prostate Cancer with 2 additional years of follow-up.  After a median follow-up of 11 years in the core age group, the relative reduction in the risk of death from prostate cancer in the screening group was 21% , and 29% after adjustment for noncompliance. The absolute reduction in mortality in the screening group was 0.10 deaths per 1000 person-years or 1.07 deaths per 1000 men who underwent randomization. The rate ratio for death from prostate cancer during follow-up years 10 and 11 was 0.62. To prevent one death from prostate cancer at 11 years of follow-up, 1055 men would need to be invited for screening and 37 cancers would need to be detected.  Analyses after 2 additional years of follow-up consolidated our previous finding that PSA-based screening significantly reduced mortality from prostate cancer but did not affect all-cause mortality.
2'13"| Anthony Miller from University of Toronto, Ontario,Canada, writes the editorial that we are left with an unsatisfactory situation, in which many practitioners will think there are insufficient data to recommend abandoning PSA screening for prostate cancer. However, the findings of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening trial, a similar update on prostate-cancer death, are more applicable to the situation in the United States, since the European Randomized Study of Screening for Prostate Cancer was conducted in a largely PSA-naive population. Therefore, an intensification of PSA screening would be unwise, and the editorialist think it would be advisable to follow the preliminary recommendations of the U.S. Preventive Services Task Force.

上掲書では、要約をさらに下記4点に絞って読むことを推奨している。

1. METHODSの「最後から一文前(penultimate sentence)」あたりでPrimary Endpointを把握する。
2. CONCLUSIONSの最初の文からPEに関連した結論を把握する。increase, decrease, reduceなどの単語がマーカー。
3. RESULTSの最初か２番目の文から比（risk ratio, hazard ratio, odds ratio）、信頼区間、P値を読む。
4. 研究デザインをMETHODSの頭で確認する。randomized clinical trial, randomly assigned, cohort study, case-control studyなどがマーカー。Critical readingの際は、CONSORTやSTROBEなどの各声明を参考に。

それぞれ漢字１字で代表させると、終結比設（zhōng jié bǐ shè）とでもなろうか、それぞれを当該論文の要約に当たって拾ってみる。目の動きは、METHODSの終わりのある中央部から、CONCLUSIONS、RESULTSと遡上してMETHODSの頭に帰る。

1. 終: mortality from prostate cancer
2. 結: significantly reduced
3. 比: rate ratio, 0.79; 95% confidence interval [CI], 0.68 to 0.91; P=0.001
4. 設: randomly assigned

確かに慣れれば、1分ほどで要約の内容は、把握できそうだが、聴き取る場合には、数字の聴解がネックになりそう。

NEJM Audio Summary - March 8, 2012

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3'18" | "Donepezil and Memantine for Moderate-to-Severe Alzheimer's Disease" by Robert Howard. From King's College London. The authors investigated whether community-living patients with Alzheimer's disease, who have moderate-to-severe disease and are already receiving donepezil, benefit from continuing treatment and whether initiating memantine at this point in the course of the disease is beneficial. Patients assigned to continue donepezil, as compared with those assigned to discontinue donepezil, had a score on the Standardized Mini-Mental State Examination that was higher by an average of 1.9 points and a score on the Bristol Activities of Daily Living Scale that was lower (indicating less impairment) by 3.0 points. Patients assigned to receive memantine, as compared with those assigned to receive memantine placebo, had a score that was an average of 1.2 points higher and a score that was 1.5 points lower, respectively.  There were no significant benefits of the combination of donepezil and memantine over donepezil alone. In patients with moderate or severe Alzheimer's disease, continued treatment with donepezil was associated with cognitive benefits that exceeded the minimum clinically important difference and with significant functional benefits over the course of 12 months.

4'47" | In editorial Lon Schneider from From University of Southern California Keck School of Medicine, Los Angeles, write that memantine appears to be helpful for the treatment of moderate-to-severe Alzheimer's disease when used alone or when replacing donepezil, however, the results of this trial do not support the typical use in the United States, and an FDA-approved use, as add-on therapy to established donepezil treatment.

和訳は、otoweltさんのブログ「呼吸器内科医」の投稿「Alzheimer病におけるドネペジルの継続は有用」を参照してください。日本神経学会による『認知症疾患治療ガイドライン２０１０』は、ドネペジル、メマンチン、ガランタミン、リバスチグミンの４剤をグレードＡとしておりますが、Archives of Neurologyに「メマンチンは、軽度アルツハイマー病患者の効果において有意差を認めなかった」と報告した論文が発表されています。周辺症状に対して、特にレヴィ小体病による幻覚では、抑肝散の効果が有名です。

NEJM Audio Summary - March 1, 2012

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Defining “Patient-Centered Medicine”, a perspective article by Charles Bardes. From Weill Cornell Medical College, New York. 

What is the proper relation between the doctor's and the patient's experiences of illness? Between a scientific understanding of disease, whatever the science of the day may be, and the subjective phenomenon of being sick? Between the subspecialist and the general physician? Between cure and care?“Patient-centered medicine” is the newest salvo in these ancient debates.

As a form of practice, it seeks to focus medical attention on the individual patient's needs and concerns, rather than the doctor's. As a rhetorical slogan, it stakes a position in contrast to which everything else is both doctor-centered and suspect on ethical, economic, organizational, and metaphoric grounds.

Patient-centered medicine is, above all, a metaphor. “Patient-centered” contrasts with “doctor-centered” and replaces a Ptolemaic universe revolving around the physician with a Copernican galaxy revolving around the patient. The flaw in the metaphor is that the patient and the doctor must coexist in a therapeutic, social, and economic relation of mutual and highly interwoven prerogatives. Neither is the king, and neither is the sun. Health relies on collaboration between the patient and the doctor, with many others serving as interested third parties. Patient and physician must therefore meet as equals, bringing different knowledge, needs, concerns, and gravitational pull but neither claiming a position of centrality. 

語彙

• the Ptolemaic system /ˌtɑləˈmeɪɪk ˌsɪstəm/
• Copernican system /kəˈpərnɪkən ˌsɪstəm/
• flaw /flɔ'ː/ 欠陥、欠点、不備
• prerogative /prirɑ'gətiv/ 特権