Case 051229 "Odontogenic keratocyst"

"An 18-Year-Old Man with a One-Month History of Nontender Left Mandibular Swelling". This CASE RECORD OF THE MASSACHUSETTS GENERAL HOSPITAL describes an 18-year-old man who reported gradual painless swelling of the left mandible. On physical examination, there was obvious facial asymmetry, with the left side of the jaw larger than the right. And odontogenic source of infection was ruled out. The painless left posterior mandibular swelling with radiographic findings of a loculated radiolucency and an associated impacted tooth favor the diagnosis of an odontogenic cyst. However, the lack of bone perforation and the circumferential appearance of the radiolucency slightly favor the diagnosis of odontogenic keratocyst. Meredith August discusses both odontogenic and nonodontogenic processes in the differential diagnosis. August also explains management of cystic lesions of the jaw.

今回は、角化嚢胞性歯原性腫瘍。

Case 051222 "Onchocerciasis"

"A 63-Year-Old Woman with a Positive Serologic Test for Syphilis and Persistent Eosinophilia", this CASE RECORD OF THE MASSACHUSETTS GENERAL HOSPITAL discusses 63-year-old woman from Cameroon who was referred to infectious-disease specialists.
She had a positive serologic test for syphilis and persistent peripheral-blood eosinophilia. Routine chest radiograph had shown a dilated aorta with calcification.
On physical examination, there was a leopard-skin appearance of the skin of the upper back, upper buttocks, and upper thighs, with scattered hypopigmented lesions.
Though she had been sexually active only with her husband and had been a widow for 15 years, her husband had had five wives. In addition the patient had previously been treated filariasis. Transthoracic echocardiogram disclosed minimal thickening of the leaflets and moderate aortic regurgitation.Snips of the patient's skin were evaluated for microfilariae.
Donna Felsenstein discusses the diagnosis, staging and management of syphillis. And Edward Ryan describes infectious causes of persistent eosinophilia and management in this case. Video clips of the transthoracic echocardiogram and of this skin snip showing mobile microfilaria may be reviewed in NEJM.org. [Original Article]  

今回は、WHOが指定した１７つのNeglected Tropical Diseases(NTD)の１つ。"mobile"の聴き取りに難渋した。名詞でモウビール、形容詞でモウブル、いずれにせよ、前方にアクセントがあって、モバイルは完全に和製英語。

Case 051215 "SLE"

"A 29-Year-Old Pregnant Woman with the Nephrotic Syndrome and Hypertension", this CASE RECORD OF THE MASSACHUSETTS GENERAL HOSPITAL describes a 29-year-old pregnant woman with systemic lupus erythematosus who was admitted to the hospital because of renal failure at 20 weeks and 6 days of gestation.
Prior to the visit the patient was been monitored for hypertensive complications of pregnancy or worsening nephritis. Fetal growth was followed with ultrasonography. As she approached the 20th week of pregnancy, marked edema and weight gain occurred, with evidence of worsening renal function. Edema and proteinuria and rising blood pressure were present at the time of admission; this triad is the hallmark of preeclampsia, but each of these findings can also be associated with a flare of lupus nephritis. During the next three weeks, proteinuria persisted, anemia and thrombocytopenia developed and worsened, and the blood pressure continued to rise. A procedure was performed.
In discussing the differential diagnosis, Winfred Williams Jr. writes that the issue is whether she was having a flare of her lupus nephritis, preeclampsia, or both. These two possibilities require radically different management strategies and, therefore, must be sorted out as quickly and efficiently as possible. Williams stresses that this is especially the case in a pregnancy in which renal failure and hypertension are progressing rapidly.

Case 051208 "Brugada syndrome"

11:49| "A 35-Year-Old Man with Cardiac Arrest while Sleeping" This CASE RECORD OF THE MASSACHUSETTS GENERAL HOSPITAL describes a 35-year-old man who screamed during sleep and became unresponsive, with agonal breathing and a bluish skin color.His partner performed mouth-to-mouth "rescue" breathing, but not chest compressions.
 Technicians from emergency medical services found him in ventricular fibrillation; normal rhythm was restored, but the patient did not regain consciousness. In the emergency department an EKG revealed ST-segment elevation, and there was evidence of pseudoephedrine in the serum. The results of cardiac catheterization were normal.
 Keith Marill discusses the issues raised by this case including the management of out-of-hospital cardiac arrest due to ventricular fibrillation both at the scene and in the emergency department. Marill also discusses the differential diagnosis of cardiac arrest in a young patient.

Further Reading

• QT延長症候群（先天性・二次性）とBrugada症候群の診療に関するガイドライン

Case 121227 "Amniotic-fluid embolism"

9:53| "A 43-Year-Old Woman with Cardiorespiratory Arrest after a Cesarean Section", a CASE RECORD OF THE MASSACHUSETTS GENERAL HOSPITAL by Jeffrey Ecker and colleagues.
A 43-year-old woman (a multigravida) was admitted to the labor and delivery service of this hospital at 36.4 weeks of gestation because of vaginal bleeding.
Marginal placenta previa was seen on obstetrical ultrasonography, and two episodes of bleeding occurred, at 27.7 weeks and 32.7 weeks of gestation, which resolved after the patient was admitted for bed rest, hydration, and the administration of betamethasone. She was advised to maintain bed rest at home. At a routine prenatal visit 8 days before this presentation (at 35.3 weeks of gestation), obstetrical ultrasonography revealed an anterior placenta with the edge covering the internal os, a finding consistent with placenta previa.
Heavy vaginal bleeding developed on the day of admission. Plans were made for emergency cesarean delivery. A healthy boy was delivered. The placenta previa was removed.
Twenty minutes after delivery, as the abdominal fascia was being closed, the patient's systolic blood pressure fell to 70 to 80 mm Hg, the pulse to 30 to 39 beats per minute, and oxygen saturation to 70 to 80%. The patient reported chest pain, and her lips became white; apnea developed rapidly thereafter, and she became unresponsive. Examination revealed pulseless electrical activity.
In situations such as this clinicians must focus promptly on a most-likely diagnosis in order to direct problem-specific therapies.

Case 051124 "MELAS"

13:24| A CASE RECORD OF THE MASSACHUSETTS GENERAL HOSPITAL describes a 61-year-old who was admitted to the hospital because of a seizure and altered mental status.
 The patient had been in good health, with the exception of mild hypertension for which she took no medications.
 On the morning of admission, her husband awoke at 4 a.m. to find her thrashing in bed, with rhythmic movements of all four extremities, for two to five minutes. She subsequently appeared groggy but alert, with a facial droop, garbled speech, and an inability to follow verbal commands.
 For the next six months, she remained aphasic and confused. During first hospitalization, the neuroimaging findings confirmed the clinical localization of the left temporo-occipital lesion, and its characteristics suggested focal metabolic dysfunction.
This neurologic syndrome occurred in the context of a urinary tract infection, and lumbar puncture revealed only elevated lactate levels, without evidence of a central nervous system infection or inflammatory response.
 Dr. Bradford Dickerson discusses differential diagnosis and management of this patient. [Original Article]

Vocabulary:

• groggy ふらふらした（グロッキーの元の語）
• garbled 不明瞭な(「文字化け」の意味もある）

Further Reading:

• Gene Reviews Japan "MELAS"

Case 051117 "Breast Cancer"

12:14| In the CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL, a 56-year-old woman was referred to the multidisciplinary breast clinic, for management of invasive breast cancer.
She presented with a 1-cm invasive ductal carcinoma of the breast.
On examination, the patient appeared well, and her vital signs were normal. There was a palpable 1.5-cm mass at the 10-o'clock position in the anterior axillary line. There was no discharge or inversion of the nipples and no lymphadenopathy. The results of routine laboratory tests revealed no abnormalities.
One month later, a right partial mastectomy, intraoperative lymphangiography, and sentinel-lymph-node biopsy of the right axilla were performed. Immunohistochemical staining detected positive tumor cells. The tumor was positive for estrogen-receptor protein and faintly positive for progesterone-receptor protein.
The patient returned to the breast clinic one month later for discussion of further management.
 The authors discuss the staging and management of breast cancer with sentinel lymph-node involvement. [Orignal Article]

Case 051110 "TEN"

10:18| This CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL describes a 10-year-old girl who was transferred to the Shriners Hospital for Children in Boston because of a bullous skin eruption, with sloughing of the skin and respiratory failure.
The patient had been well until two months before admission, when she had a generalized tonic–clonic seizure. She was examined at different hospital and treated with diazepam.
One month before admission, during an episode of gastroenteritis, intermittent twitching occurred in both legs. A diagnosis of seizure was made, and a neurologist prescribed carbamazepine.
On examination two days after the seizure, the physical and neurologic examinations showed no abnormalities.
Nine days later, the temperature rose and a rash appeared on the patient's trunk. The next day she went to the emergency room of the hospital where she had been treated previously. A diffuse, erythematous morbilliform rash with extensive confluence was present, most intensely visible on the back, trunk, and upper arms and thighs, with blanching. A diagnosis of hypersensitivity reaction was made. The carbamazepine was discontinued.  The patient was discharged to her home.
The next day, the rash had spread to involve most of her body, and vesicles had developed. On examination, diffuse, erythematous, raised lesions involved the face, trunk, back, arms and legs, and lips. Nikolsky's sign that is ready removal of the epidermis with slight tangential pressure was present.
This case record describes ??? After a protracted course of management in the burn unit, reepithelialization occurred, and the patient fully recovered.
 Dr. Vincent Liu discusses differential diagnosis of blistering skin eruption. [Original Article]

Further Reading:

• Robert S. Stern, M.D. Exanthematous Drug Eruptions N Engl J Med 2012; 366:2492-2501

"Cabot Cases" in NEJM

NEJMで長く連載されているCPCは、MGHで研修の目的で行われているカンファレンスである。合衆国のロースクールでの"Case book method"をメディカルスクールに導入したのが、Walter Bradford Cannonであった。その後、臨床と病理を突き合わせるという形式を定めたのがRichard Clarke Cabot。その創設者に敬意を表して"Cabot cases"とも呼ばれてきた。そして、いよいよ1923年10月25日 "Case 9431"がNEJM誌に登場する。冒頭は、以下の通り。

An American student of twenty-four entered March 26, March, 1923, complaining of pain and dyspnea.

ケースのナンバリングの最後の桁は、その週の何番目のケースかを示している。つまり、連載開始以前942週に渡り、MGHでこのカンファレンスが開催されていたことになる。このナンバリングは1960年12月29日号に掲載されたCase 46522まで、平均して週に2症例ずつ続くことになる。1961年からは、年毎の連番となり、１９６１年には９２症例だったものが漸減し、1967年以降は週1症例に固定され、年間50〜53症例の時代が続く。1992年からはJerome P. KassirerのClinical Problem-Solvingの連載が始まり、1995年からは各月第1週は、この新たな症例報告形式が定期連載となり、CPCはその時は掲載されず、年間40症例の掲載となって現在に至っている。この間、Audio Summaryが2005年１１月3日から開始され、CPCも約1分間にまとめられて現在まで287症例の概要が音声を通じて紹介されている。

Serious Celiac Sprue

NEJMの"Clinical Practice"のシリーズは、全文がオーディオで提供され、今回134本目を数える。ぜひMP3プレーヤに入れておきたいシリーズである。

9:13| "Celiac Disease", a clinical practice article by Alessio Fasano from University of Maryland School of Medicine, Baltimore.
• Once considered a gastrointestinal disorder that mainly affects white children, celiac disease is now known to affect persons of different ages, races, and ethnic groups, and it may be manifested without any gastrointestinal symptoms.
• Measurement of IgA anti–tissue transglutaminase antibodies is the preferred initial screening test for celiac disease because of its high sensitivity and specificity, but it performs poorly in patients with IgA deficiency (which is more common in patients with celiac disease than in the general population).
• The diagnosis is confirmed by means of upper endoscopy with duodenal biopsy, although recent guidelines suggest that biopsy may not be necessary in selected children with strong clinical and serologic evidence of celiac disease.
• Given the undisputable role of gluten in causing celiac disease enteropathy, the cornerstone of treatment is the implementation of a strict gluten-free diet for life.
• Gluten sensitivity may occur in the absence of celiac disease, and a definitive diagnosis should be made before implementing a lifelong gluten-free diet.
Listen to the full text of this article at NEJM.org.(192 words / 93 sec = 124bpm)

 上掲本の最初の提示症例がセリアック病(Celiac disease)である。なんと１５年もの間、様々な専門医、総合医の診察を受け見逃されてきた経過が語られる。カッパドキアのアレテウスの昔に記載され、その名も、"abdominal" diseaseと呼ばれ、西洋人においては、さほど珍しくもないこの病気がである。その誤診の仕組みは、ぜひ本書に目を通して頂きたい。

備えあれば…

今度の冬至に地球が滅亡するという説があるそうですが、我が家は電気不要の灯油ストーブを購入して備えています。

19:13| "Preparing Health Systems for Future Disasters", a perspective article by Irwin Redlener from Columbia University, New York.
The smooth operation and then evacuation of NYU's hospitals during and after Hurricane Sandy were remarkable. But for the future, it's important to understand what medical and public health challenges are to be expected after such megadisasters.
The first order of business is always to identify and treat storm-related casualties requiring urgent attention.
Second, potentially serious public health complications may follow large-scale storms with extensive flooding. In fact, overflow from the toxin-filled Gowanus Canal in Brooklyn is already a concern that will require close monitoring. Prolonged lack of power and heat, a real problem in the first 2 weeks after Sandy, became dangerous for the elderly, homebound patients, and small children, especially those living in low-income housing projects. There are already signs of dangerous mold infestations in dwellings soaked by rain and floods.
Third, essential supply chains must be restored. The most obvious and critical concern is ensuring that patients receiving life-critical medications or supplies have uninterrupted access.
Finally, access to health care, often a casualty of large-scale disasters, has been a major challenge in Sandy's aftermath. Offices, clinics, and hospitals were damaged, some irreparably. (211 words / 99sec = 128 wpm) [Original Article]

"irreparably"はアクセントの移動があり、ピンとこなかったが、"repair"出来ないほどに、ということ。"repair"繋がりで、JFKの言葉に次のものがあります。

The time to repair the roof is when the sun is shining.

「屋根を直すのは晴れているうちに。 」、つまり、有事に先んじて準備せよってことです。

免疫抑制状態患者におけるノロウイルス胃腸炎

日常遭遇するノロウイルス感染も免疫不全状態の患者さんにおいては様相を異にします。

8:44| "Norovirus Gastroenteritis in Immunocompromised Patients", a review article by Karin Bok from National Institutes of Health, Bethesda, Maryland.
Infectious gastroenteritis is a common, acute illness that is characteristically self-limiting, but it can become debilitating and life-threatening in immunocompromised patients. Noroviruses are major pathogens among the microbes associated with gastroenteritis in both immunocompetent and immunocompromised hosts. In the United States, noroviruses are the single most common cause of acute gastroenteritis in adults that results in a visit to the hospital emergency department, and they are second only to rotaviruses as a major cause of severe diarrhea in infants and young children. In developing countries, noroviruses are estimated to cause more than 200,000 deaths annually among children younger than 5 years of age. Noroviruses are increasingly recognized as an important cause of chronic gastroenteritis in immunocompromised patients, as reflected by the growing number of clinical case reports. A comparison of the known features of norovirus gastroenteritis in immunocompetent versus immunocompromised hosts highlights the potentially serious outcome of this illness in persons who cannot adequately clear the virus. The purpose of this review is to summarize recent developments in norovirus research that are relevant to the prevention and management of norovirus gastroenteritis in immunocompromised patients. Genetic features and emerging treatments are discussed.

注

• debilitating: 消耗性の
• second only to 〜: 〜に次いで
• relevant to 〜: 〜に関して

乳がん検診の効果

結論を言うと、マンモグラフィーによる検診は、進行癌を１人減らすためのNNTが12,500と非常に非効率だそうです。

6:04 | "Effect of Three Decades of Screening Mammography on Breast-Cancer Incidence" by Archie Bleyer from St. Charles Health System, Central Oregon.
The introduction of screening mammography in the United States has been associated with a doubling in the number of cases of early-stage breast cancer that are detected each year, from 112 to 234 cases per 100,000 women — an absolute increase of 122 cases per 100,000 women. Concomitantly, the rate at which women present with late-stage cancer has decreased by 8%, from 102 to 94 cases per 100,000 women — an absolute decrease of 8 cases per 100,000 women. With the assumption of a constant underlying disease burden, only 8 of the 122 additional early-stage cancers diagnosed were expected to progress to advanced disease. After excluding the transient excess incidence associated with hormone-replacement therapy and adjusting for trends in the incidence of breast cancer among women younger than 40 years of age, the authors estimated that breast cancer was overdiagnosed (i.e., tumors were detected on screening that would never have led to clinical symptoms) in 1.3 million U.S. women in the past 30 years. The authors estimated that in 2008, breast cancer was overdiagnosed in more than 70,000 women; this accounted for 31% of all breast cancers diagnosed.
These rusults suggests that screening is having, at best, only a small effect on the rate of death from breast cancer. (240 words / 109 sec = 132 wpm)
From NEJM Audio Summaries

注

• mammography: mæmɑ'grəfi アクセントの位置に注意
• concomitantly： 同時に　cf. concomitant chemoradiotherapy
• i.e. (latin: id est) = that is
• at best: よくても　cf. The best of men are but men at best.どんなに立派な人でも、所詮、人以上のものではない。◆ことわざ

再発性ライム病、再燃、それとも再感染？

0:51| "Differentiation of Reinfection from Relapse in Recurrent Lyme Disease" by  Robert Nadelman from New York Medical College, Valhalla.
Much controversy exists regarding whether recurrent Lyme disease is due to reinfection or relapse. These investigators used molecular typing of Borrelia burgdorferi isolates obtained from patients with culture-confirmed episodes of erythema migrans to distinguish between relapse and reinfection. The outer-surface protein C of B. burgdorferi which is expressed in early infection was found to be different at each initial and second episode. Apparently identical genotypes were identified on more than one occasion in only one patient, at the first and third episodes, 5 years apart, but different genotypes were identified at the second and fourth episodes. None of the 22 paired consecutive episodes of erythema migrans were associated with the same strain of B. burgdorferi on culture. These data show that repeat episodes of erythema migrans in appropriately treated patients were due to reinfection and not relapse.
In editorial, Allen Steere from Massachusetts General Hospital, Boston, writes that the issue of relapse versus reinfection has a broader context because of patient-advocacy groups that promote months or years of antibiotic therapy for “chronic Lyme disease.” Moreover, chronic Lyme disease has become a common diagnosis for medically unexplained pain or neurocognitive or fatigue symptoms, even when there is little or no evidence of previous B. burgdorferi infection. Even so, these patients are said to have persistent infection, which can be suppressed only with months or years of antibiotic therapy, and the therapy must be restarted when symptoms recur. As concluded by the Infectious Diseases Society of America, there is no evidence of persistent B. burgdorferi infection in human patients after recommended courses of antibiotic therapy. Although B. burgdorferi infection may persist for years in untreated patients, the weight of evidence is strongly against persistent infection as the explanation for persistent symptoms in antibiotic-treated patients with Lyme disease.  (317 words / 151 sec = 126 wpm)

この論文とは関係ありませんが、ライム病つながりで。上掲本に、下の論文にあるライム病とトカゲの関係の話が出てきます。感染症の治療は、患者、病原体、薬剤のトライアングルで考えますが、公衆衛生学的な対策は生態系全体を考慮に入れなければならないことを実感させる実例です。

• Lane RS, Quistad GB. Borreliacidal factor in the blood of the western fence lizard (Sceloporus occidentalis).  J Parasitol. 1998 Feb;84(1):29-34. 

NEJM Audio Summary - Nov 8, 2012

先日３例目の感染者が公表された新型コロナウイルス感染症の記事です。

7:37| "Isolation of a Novel Coronavirus from a Man with Pneumonia in Saudi Arabia", by Ali M. Zaki from the Dr. Soliman Fakeeh Hospital, Jeddah, Saudi Arabia. On June 24, a 60-year-old man died of progressive respiratory infection in Saudi Arabia. The previously unknown coronavirus was isolated from the sputum of a man who had presented with acute pneumonia and subsequent renal failure with a fatal outcome. The virus (called HCoV-EMC) replicated readily in cell culture, producing cytopathic effects of rounding, detachment, and syncytium formation. The virus represents a novel betacoronavirus species. The closest known relatives are bat coronaviruses. In this ariticle, the clinical data, virus isolation, and molecular identification are presented. The clinical picture was remarkably similar to that of the severe acute respiratory syndrome (SARS) outbreak in 2003 and reminds us that animal coronaviruses can cause severe disease in humans.
 In editorial, Larry Anderson, from Emory Children Center, Atlanta, Georgea writes that The global community was apparently not aware of the first case of HCoV-EMC infection until it was reported on ProMED, a website for monitoring emerging diseases, on September 20, approximately 3 months after the patient died. Luckily, there have been no new reports of cases since September 22, but local surveillance should continue. With no evidence of human-to-human transmission, the WHO currently recommends no heightened global surveillance for this virus but continued “routine surveillance for early detection and rapid response of all potential public health threats.” However, such cases provide an opportunity to reconsider response strategies. (255 words / 124 sec = 123 wpm)

NEJM Audio Summary - Nov 1, 2012

今回は、アタマジラミの治療に関する論文。日本では、ピレスロイドの１つ、フェノトリンを含むスミスリンパウダーかスミスリンシャンプーを使用するが、耐性を獲得した虫が多い欧米では、代替え治療としてイベルメクチンの内服、外用も行われるらしい。内服治療に関しては、以前にNEJMでも論文が出ている。今回は外用の効果についてです。

0:56 | "Topical 0.5% Ivermectin Lotion for Treatment of Head Lice" by David Pariser from Eastern Virginia Medical School, Norfolk. New treatments for head lice are needed. Two trials involving 765 patients investigated the efficacy and safety of a single application of a new 0.5% ivermectin lotion formulation as compared with vehicle control, an identical formulation without ivermectin, in patients with head-louse infestation. In the intention-to-treat population, significantly more patients receiving ivermectin than patients receiving vehicle control were louse-free on day 2 (94.9% vs. 31.3%) and day 15 (73.8% vs. 17.6%). The frequency and severity of adverse events were similar in the two groups. A single, 10-minute, at-home application of ivermectin was more effective than vehicle control in eliminating head-louse infestations at 1, 7, and 14 days after treatment. 

In editorial Olivier Chosidow from Hôpital Henri-Mondor, Créteil, France asks "How should head-louse infestation be managed?". With good comparative-effectiveness research still lacking, indirect comparisons support the 2010 American Academy of Pediatrics recommendations to use 1% permethrin or pyrethrin insecticide as first-line therapy. If resistance in the community has been proven or live lice are present 1 day after the completion of treatment, a switch to malathion may be necessary. Other options include wet combing or treatment with dimethicone or other topical agents, depending on the availability of the agents in the country. Nit removal is useful. Ivermectin should be the last choice, whether topical (for still-infested persons) or oral (especially for mass treatment). Management should also include more frequent checking for head-louse infestation in families and schools. (273 words / 136 sec = 120 wpm) 

NEJM Audio Summary - Oct 25, 2012（3）

Mac用のテープ起こしのためのツール"CasualTranscriber"が非常に便利で、今週３記事目。和訳は、呼吸器内科医さんの「癌患者は、抗癌剤治療に過度の期待を持つ傾向がある」を参照してください。

[00:07:16]
"Patients' expectations about effects of chemotherapy for advanced cancer", by Jane Weeks from Dana-Farber Cancer Institute, Boston. The authors characterize the prevalence of the expectation among patients with metastatic lung or colorectal cancer that chemotherapy might be curative and to identify the clinical, sociodemographic, and health-system factors associated with this expectation. Overall, 69% of patients with lung cancer and 81% of those with colorectal cancer did not report understanding that chemotherapy was not at all likely to cure their cancer. The risk of reporting inaccurate beliefs about chemotherapy was higher among patients with colorectal cancer, as compared with those with lung cancer among nonwhite and Hispanic patients, as compared with non-Hispanic white patients and among patients who rated their communication with their physician very favorably, as compared with less favorably. Educational level, functional status, and the patient's role in decision making were not associated with such inaccurate beliefs about chemotherapy. Many patients receiving chemotherapy for incurable cancers may not understand that chemotherapy is unlikely to be curative, which could compromise their ability to make informed treatment decisions that are consonant with their preferences. Physicians may be able to improve patients' understanding, but this may come at the cost of patients' satisfaction with them.
[00:08:53]
In editorial Thomas Smith from the Johns Hopkins University School of Medicine, Baltimore writes that truthful conversations that acknowledge death help patients understand their curability, are welcomed by patients, and do not squash hope or cause depression. This is not one hard conversation for which we can muster our courage but a series of conversations over time from the first existential threat to life. The editorialist recommend stating the prognosis at the first visit, appointing someone in the office to ensure there is a discussion of advance directives, helping to schedule a hospice-information visit within the first three visits, and offering to discuss prognosis and coping ("What is important for you?") at each transition. ( 322 words / 146 sec = 132 wpm)

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

NEJM Audio Summary - May 24, 2012

Excerpted Script

0:56|"Aspirin for Preventing the Recurrence of Venous Thromboembolism" by Cecilia Becattini. From University of Perugia, Italy. About 20% of patients with venous thrombosis or embolism but no defined risk factors have a recurrence within the first 2 years after stopping anticoagulation therapy. This study assessed the clinical benefit of aspirin for the prevention of recurrence after a course of treatment with vitamin K antagonists in patients with unprovoked venous thromboembolism. Venous thromboembolism recurred in 28 of the 205 patients who received aspirin and in 43 of the 197 patients who received placebo (6.6% vs. 11.2% per year). During a median treatment period of 23.9 months, 23 patients taking aspirin and 39 taking placebo had a recurrence (5.9% vs. 11.0% per year). One patient in each treatment group had a major bleeding episode. Aspirin reduced the risk of recurrence when given to patients with unprovoked venous thromboembolism who had discontinued anticoagulant treatment, with no apparent increase in the risk of major bleeding.
2:13| Richard Becker, from Duke University Medical Center, Durham, North Carolina, writes in the editorial that the findings of this study are compelling and may signal an important step in the evolution of care; however, confirmatory studies will be required to establish a role in daily clinical practice for the use of aspirin among patients who are at high risk for bleeding due to anticoagulant therapy or for whom ongoing investigations identify and subsequently validate a clinical or biomarker-based profile associated with a low risk of recurring venous thromboembolism.

これをきっかけに循環器学会のHPを覗いて見ました。いつのまにか、ガイドラインが充実しています。呼吸器学会みたいに「買ってね」というのじゃないのが嬉しい。

NEJM Audio Summary - May 17, 2012

Excerpted Script

0:54| "Warfarin and Aspirin in Patients with Heart Failure and Sinus Rhythm", by  Shunichi Homma, from Columbia University Medical Center, New York. Patients with heart failure and sinus rhythm benefit from anticoagulation. This trial assessed whether warfarin or aspirin is a better treatment for patients with a reduced left ventricular ejection fraction (LVEF) who were in sinus rhythm. The rates of the primary outcome which was the first event of ischemic stroke, intracerebral hemorrhage, or death from any cause were 7.47 events per 100 patient-years in the warfarin group and 7.93 in the aspirin group. Thus, there was no significant overall difference between the two treatments. In a time-varying analysis, the hazard ratio changed over time, slightly favoring warfarin over aspirin by the fourth year of follow-up, but this finding was only marginally significant. Warfarin, as compared with aspirin, was associated with a significant reduction in the rate of ischemic stroke throughout the follow-up period (0.72 events per 100 patient-years vs. 1.36 ). The rate of major hemorrhage was 1.78 events per 100 patient-years in the warfarin group as compared with 0.87 in the aspirin group. Among patients with reduced LVEF who were in sinus rhythm, there was no significant overall difference in the primary outcome between treatment with warfarin and treatment with aspirin. A reduced risk of ischemic stroke with warfarin was offset by an increased risk of major hemorrhage. The choice between warfarin and aspirin should be individualized.
2:47| In editorial, John Eikelboom from McMaster University, Hamilton, Ontario, Canada, writes that the results of this trial are consistent with those of three previous smaller randomized, controlled trials in showing that warfarin anticoagulant therapy, as compared with aspirin, is not associated with a reduction in mortality among patients with heart failure. This trial provides clear evidence that anticoagulant therapy prevents stroke, probably embolic stroke, in patients with heart failure who have severe systolic dysfunction, but the rates of stroke are too low to justify the routine clinical use of warfarin in most patients with heart failure, in light of the increase in the risk of bleeding.

内容は2月に行われた国際脳卒中学会で発表されたもの。著者の本間俊一教授はこのような方。

NEJM Audio Summary - May 10, 2012

Excerpted Script

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

Excerpted Script

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

Excerpted Script

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

Excerpted Script

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

Excerpted Script

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。

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