NEJM Audio Summary - Oct 25, 2012 (2)

札幌医大第一内科助教の能正勝彦先生がお名前を連ねている論文。

Excerpted Script
3:18| "Aspirin Use, Tumor PIK3CA Mutation, and Colorectal-Cancer Survival" by Xiaoyun Liao from Dana–Farber Cancer Institute,Boston.
Regular use of aspirin after a diagnosis of colon cancer has been associated with a superior clinical outcome. These authors assessed the effect of aspirin on survival among patients with mutated PIK3CA colorectal cancers might differ from the effect among those with wild-type PIK3CA tumors. Among patients with mutated-PIK3CA colorectal cancers, regular use of aspirin after diagnosis was associated with superior colorectal cancer–specific survival (multivariate hazard ratio for cancer-related death, 0.18) and overall survival (multivariate hazard ratio for death from any cause, 0.54). In contrast, among patients with wild-type PIK3CA, regular use of aspirin after diagnosis was not associated with colorectal cancer–specific survival (multivariate hazard ratio, 0.96) or overall survival (multivariate hazard ratio, 0.94). Regular use of aspirin after diagnosis was associated with longer survival among patients with mutated-PIK3CA colorectal cancer, but not among patients with wild-type PIK3CA cancer. The findings from this molecular pathological epidemiology study suggest that the PIK3CA mutation in colorectal cancer may serve as a predictive molecular biomarker for adjuvant aspirin therapy.
Boris Pasche from University of Alabama, Birmingham writes in editorial that assuming these findings are confirmed in large prospective studies, one may predict that the PIK3CA mutation status of colorectal tumors will become a useful biomarker that may guide adjuvant therapy. Since more than one of six primary colorectal tumors harbors PIK3CA mutations,targeted use of adjuvant aspirin could have a major effect on the treatment of colorectal cancer. Aspirin may well become one of the oldest drugs to be used as a 21st-century targeted therapy. (304 words / 145 sec = 126 wpm)

NEJM Audio Summary - Oct 25, 2012

３週連続で選挙記事が続いております。

14:38| "Understanding Health Care in the 2012 Election", a special report by Robert Blendon from the Harvard School of Public Health, Boston.
Health care is playing a greater role in this presidential election than in many other recent ones. However, the economy dominates most voters' thinking in terms of their priorities for choosing a candidate. But in a close election, the two candidates' stands on health care issues could help swing the balance among some voters. Debates about the future role of government in health care are likely to figure prominently in the remainder of this presidential campaign. In this article the authors examine the role of health care in the 2012 election by drawing on the results of 37 independent telephone polls. They found that at this point in the election cycle, with the exception of voters focused on abortion, those who select health care as their top voting issue are much more likely to support the policy positions of President Obama than those of Romney. (166 words / 63 sec = 158 wpm)

NEJM Audio Summary - Oct 18, 2012

いつもの大統領選挙以上にNEJMでは選挙に関する記事を取り上げている。というのも、オバマ政権で2010年制定された「患者保護並びに医療費負担適正化法」の行方が今後のアメリカの医療に与える影響が大きいからなのだろう。双方の候補の主張に対する論説が、オーディオ素材込みで掲載されている。

いまさらながらの感もあるが、大統領選挙の全体像に関しては、ConnectUSAのコンテンツが分かりやすい。

Excerpted Script

15:24| "Health Care Policy under President Romney", a perspective article by Eli Adashi, from Brown University, Providence, Rhode Island.
When Mitt Romney campaigned in 2002 to become governor of Massachusetts, he offered no hint that he would lead the enactment of the most consequential state health care reform law in U.S. history. Yet as early as February 2003, Governor Romney began to intimate his intention to engineer the law promising near-universal health insurance coverage that was enacted in 2006. Though plans touted in campaign rhetoric often differ from subsequent policy actions, this gap is especially relevant in considering potential federal health policy under a President Romney. Although Romney has offered many opinions and comments as a presidential candidate, he has not provided any detailed blueprint of his plans for U.S. health system reform, and his proposals provoke questions more than they provide answers. But a review of Romney's campaign website, public addresses, debates, interviews, and other statements reveals some essential elements of his health policy intentions.
Mitt Romney says he'd repeal much of the Affordable Care Act.
His replacement proposals would provide no meaningful security to people who would lose the law's coverage protections. Other policy aims would shift growing Medicare costs to beneficiaries, curtail Medicaid's benefits and shrink its enrollment, and reduce all federal health spending.
17:02| The Shortfalls of “Obamacare”, a perspective article by Gail Wilensky from Project HOPE, Bethesda, Maryland.
U.S. health care suffers from three major problems: millions of people go without insurance, health care costs are rising at unaffordable rates, and the quality of care is not what it should be. The ACA primarily addresses the first — and easiest — of these problems by expanding coverage to a substantial number of the uninsured. Solutions to the other two remain aspirations and promises.
The law's most controversial provision remains the individual mandate, which requires people either to have insurance coverage or to pay a penalty. The penalty for not having insurance is very small, particularly for younger people with modest incomes.  A mandate cannot work without a credible threat that noncompliance will be costly. Moreover, although the ACA expands coverage, it ignores the structural problems in the organization and reimbursement of care.
Most troubling, the ACA contains no reform of the way physicians are paid, which is the most dysfunctional part of the Medicare program.
Finally, as Medicare has since its inception, the ACA focuses all its pressure to reduce spending and improve quality of care on clinicians and institutional providers through regulatory means, rather than trying to harness market forces. (431 words / 191 sec = 135 wpm)

NEJM Audio Summary - Oct 11, 2012

今週のNEJMでは医療政策に関してオバマ、ロムニー両候補が寄稿している。日本のマスコミは中国の話題が多く、米大統領選挙が霞んでいる感があるが、TPP（環太平洋戦略的経済連携協定）を考えると、前回の選挙以上に日本の将来に関わる選挙なのかもしれない。医療政策の論点は、西川 珠子氏のレポート「重要争点に浮上したメディケア改革」などを参考にすると分かりやすい。

では、Podcastの該当部位のスクリプトです。

13:34| "Health care reform and presidential candidates"
The editors asked the Democratic and Republican presidential nominees, President Barack Obama and former Massachusetts Governor Mitt Romney, to describe their health care platforms and their visions for the future of American health care.
President Barack Obama says that Obamacare is moving America toward greater health security. In his second term, he would follow through with implementation and aim to fix Medicare's payment formula, support life-sciences research, and keep Medicare and Medicaid strong.
Governor Mitt Romney says he would repeal Obamacare and replace it with common-sense, patient-centered reforms suited to the challenges we face. In the health care system he envisions, choice and competition would result in better quality at lower cost.
Statements from both of presidential candidates are available at NEJM.org.
(133 words / 60 sec = 133 wpm)

蛇足ですが、応募していたNEJM創刊号復刻版の抽選に当選しました！

NEJMに日本未破裂脳動脈瘤悉皆調査（UCAS Japan）結果

NEJMに日本の未破裂動脈瘤の自然経過のまとめが報告された。結論から直径ごとの診断後１年間で破裂する確率をまとめると下記の表にまとめられる。N Engl J Med 2012; 366:2474-2482

動脈瘤径(mm)	診断後１年間に破裂する確率(%)
3-4	0.36
5-6	0.50
7-9	1.69
10-24	4.37
25以上	33.40

１年での確率で言われてもピンとこないかもしれません。そこで、P：x年以内に破裂する確率、p：上記表の径から導かれる確率、x：診断後経過年数として大雑把なモデルで、５年後、１０年後、２０年後に破裂している確率を計算してみましょう。

rupture <- function(x, p) {
    1 - (1 - p/100)^x
}
x <- c(5, 10, 20)

径が5-6mmの場合、５年後、１０年後、２０年後に破裂している確率はそれぞれ、

rupture(x, 0.5)

## [1] 0.02475 0.04889 0.09539

径が7-9mmの場合、５年後、１０年後、２０年後に破裂している確率はそれぞれ、

rupture(x, 1.69)

## [1] 0.08169 0.15671 0.28886

径10-24mmがの場合、５年後、１０年後、２０年後に破裂している確率はそれぞれ、

rupture(x, 4.37)

## [1] 0.2002 0.3604 0.5908

径が>25mmの場合、５年後、１０年後、２０年後に破裂している確率はそれぞれ、

rupture(x, 33.4)

## [1] 0.8690 0.9828 0.9997

見通しが良いようにグラフ化すると、

x <- c(1:30)
plot(x, rupture(x, 0.5), type = "l", lty = 1, xlim = c(0, 30), ylim = c(0, 
    1), ann = F)
par(new = T)
plot(x, rupture(x, 1.69), type = "l", lty = 2, xlim = c(0, 30), ylim = c(0, 
    1), ann = F)
par(new = T)
plot(x, rupture(x, 4.37), type = "l", lty = 3, xlim = c(0, 30), ylim = c(0, 
    1), ann = F)
par(new = T)
plot(x, rupture(x, 33.4), type = "l", lty = 4, xlim = c(0, 30), ylim = c(0, 
    1), main = "脳動脈瘤のサイズと予後", xlab = "診断後年数", 
    ylab = "破裂する確率")
legend(5, 0.8, c("5-6mm", "7-9mm", "10-24mm", ">25"), lty = 1:4)

NEJM Audio Summary - June 7, 2012

Excerpted Script

0:47| "Delamanid for Multidrug-Resistant Pulmonary Tuberculosis", by Maria Tarcela Gler, from the Makati Medical Center, Manila in the Philippines. In this study patients with sputum culture–positive multidrug-resistant pulmonary tuberculosis received 2 months of treatment with delamanid, a novel antituberculosis medication, at a higher or lower dose, or placebo in combination with a background drug regimen developed according to World Health Organization guidelines. Among patients who received a background drug regimen plus 100 mg of delamanid twice daily, 45.4% had sputum-culture conversion in liquid broth at 2 months, as compared with 29.6% of patients who received a background drug regimen plus placebo. Likewise, as compared with the placebo group, the group that received the background drug regimen plus 200 mg of delamanid twice daily had a higher proportion of patients with sputum-culture conversion (41.9%). The findings were similar with assessment of sputum-culture conversion in solid medium. Delamanid at either dose did not have dose-limiting toxicity; however, patients who received delamanid plus the background drug regimen had more episodes of QT-interval prolongation on scheduled ECG. Delamanid was associated with an increase in sputum-culture conversion at 2 months among patients with multidrug-resistant tuberculosis. This finding suggests that delamanid could enhance treatment options for multidrug-resistant tuberculosis.
2:32| "National Survey of Drug-Resistant Tuberculosis in China", by Yanlin Zhao(赵雁林), from the Chinese Center for Disease Control and Prevention, Beijing. In 2007, the authors carried out a national survey of drug-resistant tuberculosis in China. Among 3037 patients with new cases of tuberculosis and 892 with previously treated cases, 5.7% and 25.6%, respectively, had multidrug-resistant (MDR) tuberculosis. Approximately 8% of the patients with MDR tuberculosis had extensively drug-resistant (XDR) tuberculosis. In 2007, there were 110,000 incident cases of MDR tuberculosis and 8200 incident cases of XDR tuberculosis. Most cases of MDR and XDR tuberculosis resulted from primary transmission. Patients with multiple previous treatments who had received their last treatment in a tuberculosis hospital had the highest risk of MDR tuberculosis (adjusted odds ratio, 13.3). Among 226 previously treated patients with MDR tuberculosis, 43.8% had not completed their last treatment; most had been treated in the hospital system. Among those who had completed treatment, tuberculosis developed again in most of the patients after their treatment in the public health system. China has a serious epidemic of drug-resistant tuberculosis. MDR tuberculosis is linked to inadequate treatment in both the public health system and the hospital system, especially tuberculosis hospitals; however, primary transmission accounts for most cases.
4:28| Richard Chaisson, from Johns Hopkins University School of Medicine, Baltimore, writes in the editorial that MDR and XDR tuberculosis are now widespread throughout the world, with the increase driven largely by transmission. Efforts to control drug-resistant tuberculosis can no longer focus solely on high-risk patients but must be incorporated into basic tuberculosis-control programs. Creating the capacity to make an accurate diagnosis of MDR tuberculosis and to treat the patients with this disease appropriately is a monumental task but one that cannot be avoided if tuberculosis is to be contained.

呼吸器内科医さんの「ランダム化プラセボ対照試験により多剤耐性結核におけるDelamanidの有効性が証明」を参照。その他、WHOの結核治療ガイドライン、中国CDCの結核のページなど。

NEJM Audio Summary - May 31, 2012

Excerpted Script

0:46| "Drotrecogin Alfa (Activated) in Adults with Septic Shock" by V. Marco Ranieri, from Università di Torino, Turin, Italy. 0:46| The efficacy of drotrecogin alpha (activated) (DrotAA) for sepsis has been controversial. This study tested the hypothesis that DrotAA, as compared with placebo, would reduce mortality in patients with septic shock. At 28 days, 223 of 846 patients (26.4%) in the DrotAA group and 202 of 834 (24.2%) in the placebo group had died. At 90 days, 34.1% in the DrotAA group and 32.7% in the placebo group had died. Among patients with severe protein C deficiency at baseline, 28.7% in the DrotAA group had died at 28 days, as compared with 30.8% in the placebo group. Similarly, rates of death at 28 and 90 days were not significantly different in other predefined subgroups, including patients at increased risk for death. Serious bleeding during the treatment period occurred in 10 patients in the DrotAA group and 8 in the placebo group. DrotAA did not significantly reduce mortality at 28 or 90 days, as compared with placebo, in patients with septic shock.
2:17| Richard Wenzel, from the Virginia Commonwealth University, Richmond, writes in the editorial that this large and well-conducted study should end any further pursuit of a niche for DrotAA in the treatment of sepsis. The investigators' findings provide a sad chapter in the noble quest for a truly effective adjunct for the treatment of septic shock. This setback should inspire a redoubling of efforts to seek new approaches to treatment that are based on a more crystalline view of the biology of sepsis.

日本語では、呼吸器内科医「敗血症性ショックにおけるザイグリスdrotrecogin alfa (DrotAA)は死亡率改善もたらさず」とか、ID CONFERENCEの「さようならプロテインC」とかも