NEJM Audio Summary - April 19, 2012

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0'47"| "Comparative Effectiveness of Revascularization Strategies" by William  Weintraub, from Christiana Care Health System, Newark, Delaware
A large registry on percutaneous coronary intervention (PCI) and a large registry on coronary-artery bypass grafting (CABG) were linked to claims records, with data adjusted for propensity score, to compare clinical outcomes.  Among patients 65 years of age or older who had two-vessel or three-vessel coronary artery disease without acute myocardial infarction, 86,244 underwent CABG and 103,549 underwent PCI. The median follow-up period was 2.67 years. At 1 year, there was no significant difference in adjusted mortality between the groups (6.24% in the CABG group as compared with 6.55% in the PCI group). At 4 years, there was lower mortality with CABG than with PCI (16.4% vs. 20.8%). Similar results were noted in multiple subgroups and with the use of several different analytic methods. In this observational study, we found that, among older patients with multivessel coronary disease that did not require emergency treatment, there was a long-term survival advantage among patients who underwent CABG as compared with patients who underwent PCI.
2'21"|  Laura Mauri from Brigham and Women's Hospital, Boston, writes in the editorial that the validity of these findings rests largely on a determination of whether adequate control for confounding was possible.  As might be expected in a nonrandomized cohort, patients in the two treatment groups differed significantly with respect to age, sex, coexisting conditions, and urgency of treatment. Propensity scores (which were used to estimate the probability, on the basis of patient and hospital characteristics, that patients would be selected for CABG) were also quite divergent, indicating a strong selection bias. Even with the findings adjusted for propensity score, the authors state their conclusions cautiously, and they acknowledge the possibility of residual confounding.

内容については、六号通り診療所所長のブログの「心臓のバイパス手術とカテーテル治療の予後を比較する」をご参照ください。何故、一科学者でもあられる天皇陛下がCABGを選択されたかが理解できます。

NEJM Audio Summary - April 12, 2012

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8'23"| "A Randomized Trial of Rectal Indomethacin to Prevent Post-ERCP Pancreatitis", by B. Joseph Elmunzer, from University of Michigan Medical Center, Ann Arbor. This study involving 602 patients at increased risk for pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) evaluated the efficacy of prophylactic rectal indomethacin for the prevention of post-ERCP pancreatitis. The majority of patients (82%) had a clinical suspicion of sphincter of Oddi dysfunction. Post-ERCP pancreatitis developed in 9.2% patients in the indomethacin group and in 16.9% patients in the placebo group. Moderate-to-severe pancreatitis developed in 4.4% patients in the indomethacin group and in 8.8% patients in the placebo group. Among patients at high risk for post-ERCP pancreatitis, rectal indomethacin significantly reduced the incidence of the condition.

へー！！！　NNT計算すると、100 / (16.9 - 8.8) = 12.345679 って話。

参考

• 内科開業医のお勉強日記「ERCP膵炎：検査後直腸内インドメタシン投与でリスク低下」
• 呼吸器内科医「ERCP後膵炎の発症予防にインドメタシン直腸内投与が有効」

NEJM Audio Summary - April 5, 2012

まずは、よい告知から。NEJMのiPadアップが発表されました。

0'59"| Thanks to a newly built software app, the Journal can now be downloaded and read in an issue format on the iPad. The NEJM iPad Edition is now available in the iTunes App Store at no charge. The app allows downloads of the full text of single issues, including figures and tables, beginning with the first issue of 2012. Individual subscribers to the Journal can log on to the new iPad app using the same username and password that they use at NEJM.org. We invite readers who use the iPad to try the new app. As always, feedback is welcome. 

NEJM読むためだけにでも、iPad買ってもいいかも。Android版については、ノーコメントですから。

次は、悪い告知(Cancer diagnosis)後に自殺や心血管死亡が増えるという論文。

6'56"| "Suicide and Cardiovascular Death after a Cancer Diagnosis" by Fang Fang. From Karolinska Institutet, Stockholm. Receiving a diagnosis of cancer is a traumatic experience that may trigger immediate adverse health consequences beyond the effects of the disease or treatment. This study of more than 6 million Swedes during 1991–2006 estimated the risk of death from suicide or cardiovascular diseases among all patients in whom cancer had recently been diagnosed. As compared with cancer-free persons, the relative risk of suicide among patients receiving a cancer diagnosis was 12.6 during the first week (29 patients) and 3.1 during the first year (260 patients). The relative risk of cardiovascular death after diagnosis was 5.6 during the first week (1318 patients) and 3.3 during the first 4 weeks (2641 patients). The risk elevations decreased rapidly during the first year after diagnosis. Increased risk was particularly prominent for cancers with a poor prognosis. In this large cohort study, patients who had recently received a cancer diagnosis had increased risks of both suicide and death from cardiovascular causes, as compared with cancer-free persons. 

 著者のFang Fangという先生、カロリンスカ研究所のプレスリリースを見ると、やはり東洋系の方のようだ。日本では、アングロサクソン風の告知が当たり前になってきたが、まだまだ中華圏やラテン文化圏では、告知率はそんなに高くはないという報告を読んだことがある。何でもかんでも告知するということに対して一石を投じる研究結果です。

NEJM Audio Summary - March 29, 2012

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7'44"| "Lifestyle Change and Mobility in Obese Adults with Type 2 Diabetes" by  W. Jack Rejeski, from Wake Forest University, Winston-Salem, North Carolina.
This trial investigated whether an intensive lifestyle intervention to produce weight loss and increased fitness would slow loss of mobility among obese patients with type 2 diabetes.  At year 4, among 2514 adults in the lifestyle-intervention group, 20.6% had severe disability and 38.5% had good mobility; the numbers among 2502 participants in the support group were 26.2% and 31.9%, respectively. The lifestyle-intervention group had a relative reduction of 48% in the risk of loss of mobility, as compared with the support group. Both weight loss and improved fitness (as assessed on treadmill testing) were significant mediators of this effect. Adverse events that were related to the lifestyle intervention included a slightly higher frequency of musculoskeletal symptoms at one year. Weight loss and improved fitness slowed the decline in mobility in overweight adults with type 2 diabetes.

雨で雪もだいぶ解けたことだし、そろそろジョギング再開ですね。

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。