NEJM Audio Summary - May 10, 2012

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0:41| "Continuous Lenalidomide Treatment for Newly Diagnosed Multiple Myeloma" by Antonio Palumbo, from the University of Turin, Italy.
Lenalidomide has tumoricidal and immunomodulatory activity against multiple myeloma. This study compared melphalan–prednisone–lenalidomide induction followed by lenalidomide maintenance (MPR-R) with melphalan–prednisone–lenalidomide (MPR) or melphalan–prednisone (MP) followed by placebo in patients 65 years of age or older with newly diagnosed multiple myeloma.  The median progression-free survival was significantly longer with MPR-R (31 months) than with MPR (14 months) or MP (13 months). Response rates were superior with MPR-R and MPR (77% and 68%, respectively, vs. 50% with MP). After induction therapy, a landmark analysis showed a 66% reduction in the rate of progression with MPR-R  that was age-independent. MPR-R significantly prolonged progression-free survival in patients with newly diagnosed multiple myeloma who were ineligible for transplantation, with the greatest benefit observed in patients 65 to 75 years of age. 

多発性骨髄腫、クリニックで診療していると、ともすると鑑別診断からこぼれ落ちそうになる疾患だ。その治療に関し、サリドマイド誘導体の「レナリドミド」の有効性が話題になっている。日本でも薬価収載され、１日25㎎、１ヶ月に21日間服用し7日間休薬するスケジュールの場合、１ヶ月のレナリドミドの費用は、8,861円×５カプセル×21日 ＝ 930,405円で、１割負担で 93,040円となります。治療したくとも放置せざるを得ない患者さんの存在が懸念されます。

NEJM Audio Summary - May 3, 2012

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0:48| "Strategies of Radioiodine Ablation in Patients with Low-Risk Thyroid Cancer",
by Martin Schlumberger, from Institut de Cancérologie Gustave Roussy, Villejuif, France. This trial compared two thyrotropin-stimulation methods and two 131I doses for postoperative ablation in patients with low-risk thyroid cancer.  In the 684 patients with data that could be evaluated, ultrasonography of the neck was normal in 652 (95%), and the stimulated thyroglobulin level was 1.0 ng per milliliter or less in 621 of the 652 patients (95%) without detectable thyroglobulin antibodies. Thyroid ablation was complete in 631 of the 684 patients (92%). The ablation rate was equivalent between the 131I doses and between the thyrotropin-stimulation methods. The use of recombinant human thyrotropin and low-dos(1.1 GBq) postoperative radioiodine ablation may be sufficient for the management of low-risk thyroid cancer.
4:40| "Two-Year Outcomes after Transcatheter or Surgical Aortic-Valve Replacement", by Susheel Kodali, from Columbia University Medical Center and New York Presbyterian Hospital, New York. This study provides 2-year data from the PARTNER trial, in which patients with aortic stenosis received transcatheter aortic-valve replacement (TAVR) or surgical replacement. The rates of death from any cause were similar in the TAVR and surgery groups (hazard ratio with TAVR, 0.90) and at 2 years were 33.9% in the TAVR group and 35.0% in the surgery group. The frequency of all strokes during follow-up did not differ significantly between the two groups. At 30 days, strokes were more frequent with TAVR than with surgical replacement (4.6% vs. 2.4%); subsequently, there were 8 additional strokes in the TAVR group and 12 in the surgery group. Improvement in valve areas was similar with TAVR and surgical replacement and was maintained for 2 years. Paravalvular regurgitation was more frequent after TAVR, and even mild paravalvular regurgitation was associated with increased late mortality. This 2-year follow-up of patients in the PARTNER trial supports TAVR as an alternative to surgery in high-risk patients. The two treatments were similar with respect to mortality, reduction in symptoms, and improved valve hemodynamics, but paravalvular regurgitation was more frequent after TAVR and was associated with increased late mortality.

今回からCMEの指定のある記事の部分を取り上げることにする。

NEJM Audio Summary - April 26, 2012

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0:49| "Bariatric Surgery versus Intensive Medical Therapy in Obese Patients with Diabetes", by Philip Schauer from Cleveland Clinic, Cleveland, Ohio.
This randomized controlled study of 150 obese patients with type 2 diabetes determined the efficacy of intensive medical therapy alone versus medical therapy plus Roux-en-Y gastric bypass or sleeve gastrectomy. The proportion of patients with the primary end point,  which was glycated hemoglobin level of 6% or less 12 months after treatment, was 12% in the medical-therapy group versus 42% in the gastric-bypass group and 37% in the sleeve-gastrectomy group. Glycemic control improved in all three groups, with a mean glycated hemoglobin level of 7.5% in the medical-therapy group, 6.4% in the gastric-bypass group, and 6.6% in the sleeve-gastrectomy group. Weight loss was greater in the gastric-bypass group and sleeve-gastrectomy group (−29.4 kg and −25.1 kg, respectively) than in the medical-therapy group (−5.4 kg). In obese patients with uncontrolled type 2 diabetes, 12 months of medical therapy plus bariatric surgery achieved glycemic control in significantly more patients than medical therapy alone. Further study will be necessary to assess the durability of these results.
1:44| "Bariatric Surgery versus Conventional Medical Therapy for Type 2 Diabetes", by Geltrude Mingrone from Università Cattolica S. Cuore, Rome.
This trial compared the efficacy of two types of bariatric surgery (gastric bypass and biliopancreatic diversion) with conventional medical therapy in severely obese patients with type 2 diabetes. At 2 years, diabetes remission had occurred in no patients in the medical-therapy group versus 75% in the gastric-bypass group and 95% in the biliopancreatic-diversion group. Age, sex, baseline BMI, duration of diabetes, and weight changes were not significant predictors of diabetes remission at 2 years or of improvement in glycemia at 1 and 3 months. At 2 years, the average baseline glycated hemoglobin level (8.65%) had decreased in all groups, but patients in the two surgical groups had the greatest degree of improvement (average glycated hemoglobin levels, 7.69% in the medical-therapy group, 6.35% in the gastric-bypass group, and 4.95% in the biliopancreatic-diversion group).  In severely obese patients with type 2 diabetes, bariatric surgery resulted in better glucose control than did medical therapy. Preoperative BMI and weight loss did not predict the improvement in hyperglycemia after these procedures.
2:42| In editorial Paul Zimmet from the Baker IDI Heart and Diabetes Institute, Melbourne, Australia, writes that these studies are likely to have a major effect on future diabetes treatment. Nevertheless, more studies are needed, particularly those that may provide better prediction of success and the expected duration of remission and long-term complications. Meanwhile, the success of various types of bariatric surgery suggests that they should not be seen as a last resort. Such procedures might well be considered earlier in the treatment of obese patients with type 2 diabetes.

「肥満手術」って、肥満症が異常に多い彼の国での話かと思いきや、先進国の中では、むしろ日本が異常に少ないのだそうだ。（参照："Metabolic/Bariatric Surgery Worldwide 2008"[PDF]）そして、そんな我が国でも2010年に日本肥満症治療学会で「日本における高度肥満症に対する安全で卓越した外科治療のためのステートメント2010」[PDF]なんてもんが公開されていた。考えようによっては、効くかどうかわからないダイエット商品よりも、手術の質が担保されれば、手術のほうが倫理的と言えるかもしれないが…

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。