ボンソワール書房日誌 Les Éditions Bonsoir Journal

G 薬物は「期待」すると，よく効く可能性がある：BBC News - Negative experiences can stop painkillers working

リンク: BBC News - Negative experiences can stop painkillers working.

ちょっとわかりにくい記事ですが，いくら強力な鎮痛薬を与えられても，鎮痛薬を服用しているという意識がないと，痛みはおさまらないということのようです。薬物に対する「期待」が，痛みを和らげてくれる，つまり，薬物の効果を増してくれます。

A patient's belief that a drug will not work can become a self fulfilling prophecy, according to researchers.

They showed the benefits of painkillers could be boosted or completely wiped out by manipulating expectations.

The study, published in Science Translational Medicine, also identifies the regions of the brain which are affected.

Experts said this could have important consequences for patient care and for testing new drugs.

Heat was applied to the legs of 22 patients, who were asked to report the level of pain on a scale of one to 100. They were also attached to an intravenous drip so drugs could be administered secretly.

The initial average pain rating was 66. Patients were then given a potent painkiller, remifentanil, without their knowledge and the pain score went down to 55.

They were then told they were being given a painkiller and the score went down to 39.

Then, without changing the dose, the patients were then told the painkiller had been withdrawn and to expect pain, and the score went up to 64.

So even though the patients were being given remifentanil, they were reporting the same level of pain as when they were getting no drugs at all.

Professor Irene Tracey, from Oxford University, told the BBC: "It's phenomenal, it's really cool. It's one of the best analgesics we have and the brain's influence can either vastly increase its effect, or completely remove it."

The study was conducted on healthy people who were subjected to pain for a short period of time. She said people with chronic conditions who had unsuccessfully tried many drugs for many years would have built up a much greater negative experience, which could impact on their future healthcare.

Professor Tracey said: "Doctors need more time for consultation and to investigate the cognitive side of illness, the focus is on physiology not the mind, which can be a real roadblock to treatment."

Brain scans during the experiment also showed which regions of the brain were affected.

The expectation of positive treatment was associated with activity in the cingulo-frontal and subcortical brain areas while the negative expectation led to increased activity in the hippocampus and the medial frontal cortex.

Professor Anthony Jones, Salford Royal Hospitals NHS Foundation Trust, said: "Work from our own lab and those of others indicates that expectations are a key driver to pain perception and to placebo analgesic effects. So this provides further confirmation of that idea in relation to drug effects.

"This has been demonstrated previously in relation to nitrous oxide analgesic effects, but the current study provides good evidence that this phenomenon is not due to the subject saying what they think the investigator wants to hear."

The researchers also say clinical trials, which are used to determine the effectiveness of drugs, should be modified.

"Rather than seeking to control for psychological components, trial designs could be developed that aim to maximize the effects of therapeutic agents by integrating the effects of expectation and active treatment."

G ビスフォスフォネートは，大腸癌になるリスクを減らす：Popular Bone Drugs Linked to Reduced Colon Cancer Risk - Yahoo! News

リンク: Popular Bone Drugs Linked to Reduced Colon Cancer Risk - Yahoo! News.

骨粗鬆症の治療などに使われるビスフォスフォネートは，大腸癌になるリスクを減らす可能性がある。スタチン系抗コレステロール薬と類似した作用機序。乳癌のリスクを減らす可能性も。

TUESDAY, Feb. 15 (HealthDay News) -- People who take drugs called bisphosphonates to prevent bone loss may also reduce their risk of developing colorectal cancer by almost 60 percent compared to those not on the drugs, a new study suggests.

Bisphosphonates include such common drugs as Fosamax (alendronate), Boniva (ibandronate), Actonel (risedronate) and Reclast (zoledronic acid). These drugs work by increasing bone thickness, thereby reducing the risk of fractures, the researchers said.

In prior studies, bisphosphonates have already been shown to be associated with a reduced odds for breast cancer.

"These [new] findings are meaningful because they point to a possible protective effect of this class of drugs being relevant to prevention of many different cancers," said lead researcher Dr. Gad Rennert, from the Technion-Israel Institute of Technology Faculty of Medicine and chairman of the department of community medicine and epidemiology at the Carmel Medical Center of Clalit Health Services in Haifa, Israel.

"This is [similar] to the effect that we and others have shown for [cholesterol-lowering] statins," he said, noting that "bisphosphonates and statins share the same metabolic pathway."

The results of the U.S. National Cancer Institute-supported study are published in the Feb. 14 issue of the Journal of Clinical Oncology.

For the study, Rennert's team collected data on almost 1,900 postmenopausal women who took part in the Molecular Epidemiology of Colorectal Cancer study, which is a population-based trial in northern Israel.

The researchers found that taking bisphosphonates, mostly Fosamax, for at least a year was associated with a significant 59 percent reduction in relative risk for colorectal cancer.

"The magnitude of the reduced risk is less important because this is an association study; however, it is very significant after controlling for a dozen other known risk factors," Rennert said.

They took into account factors such as family history, ethnic background, diet, physical activity, weight, vitamin D consumption and the use of other drugs such as aspirin, statins and hormone replacement therapy.

The findings in this study show that bisphosphonates are associated with a reduced risk of developing colorectal cancer, but they cannot confirm a causal effect -- that is, the study doesn't prove that the use of bisphosphonates is responsible for the lower risk of colorectal cancer.

However, the lowered risk of colorectal cancer seen with bisphosphonates may be due to the way the drug acts in the body, which is similar to how cholesterol-lowering drugs called statins work, according to Rennert. These same researchers also found in another study that statin use also reduced the risk of colorectal cancer, he noted.

"We also found a similar effect last year with risk of breast cancer, which has already been replicated by three other groups," Rennert added.

A randomized trial is need to prove that bisphosphonates are protective against colorectal cancer, Rennert said. "It should be relatively easy, as it seems that all that is needed is a year of treatment to see the effect," he said.

The researchers noted, however, that the risks of using bisphosphonates include the possibility, in rare cases, of osteonecrosis of the jaw (destruction of the jawbone or jaw tissue). Bisphosphonates used for osteoporosis have also been linked to a rare fracture of the thigh, according to the U.S. Food and Drug Administration.

"The adverse effects profile is of major importance if bisphosphonates are going to be recommended for cancer prevention in healthy people," the study authors cautioned.

Commenting on the study, Eric Jacobs, Strategic Director of Pharmacoepidemiology at the American Cancer Society, said that "the lower risk of colorectal cancer risk seen among bisphosphonate users in this study is intriguing."

However, these results should be interpreted with caution and require confirmation by additional studies, he said. "Results from the only other study of bisphosphonate use and colorectal cancer, a recent large study from the United Kingdom, do not support an important protective effect," Jacobs noted.

Fortunately, there are other proven ways to help lower risk of colorectal cancer, he said. "In particular, all Americans, 50 or older, should get a screening test so that precancerous polyps can be detected and removed before they turn into cancer."

G 国内後発薬シェア、09年度20％に拡大 協会調べ

リンク: いきいき健康.

後発薬のシェアが20％になったという記事です。まだまだ少ないといえるでしょうが，その分，新薬は高価になっているようにも感じます。ジェネリックは安全性が保証されていないと言う人は少なくありませんが，安全でないなら安全にするよう働きかけるのが筋なのであって，たいがい何らかの利害がからんで発言していると，心得たほうがよいです。

（以下引用です）

国内後発薬シェア、09年度20％に拡大　協会調べ

　後発医薬品（ジェネリック）メーカーで構成する日本ジェネリック製薬協会（東京・中央）は１日、後発薬シェア調査をまとめた。2009年度の出荷数量ベースのシェアは20.3％、薬価ベースは8.5％だった。09年度から調査方式を変更したため、前年度との単純比較はできないが、政府による使用促進策の効果もあり、シェアは拡大傾向にあるという。
　数量シェアの内訳は内用薬が20.5％、注射薬が23.2％、外用薬が16.9％。10年４～６月の速報値は調剤報酬改定によって調剤薬局での利用が進んだことから数量シェアは22.4％、金額シェアは9.2％とさらに伸びた。

G ビタミンKの影響のない抗凝固薬：納豆食べても大丈夫！脳卒中予防の新薬発売へ : 医療ニュース : yomiDr./ヨミドクター(読売新聞)

リンク: 納豆食べても大丈夫！脳卒中予防の新薬発売へ : 医療ニュース : yomiDr./ヨミドクター(読売新聞). 　

「ワーファリンの禁忌といえば？――納豆」が正解でしたが，新薬が発売される模様。

（以下引用です）

　血管を詰まらせる血栓をできにくくして脳卒中を予防する新しい抗凝固薬の製造・販売が２１日に承認され、今春にも国内で発売される見通しとなった。

　従来薬「ワーファリン」は、納豆を食べると効かなかったが、新薬は食べ合わせなどの影響はない。

　独製薬大手べーリンガーインゲルハイムが開発した「プラザキサ」（成分名ダビガトラン・エテキシラート）。血液を固めるトロンビンという酵素に直接作用する。心臓病の一種の「心房細動」の患者が１日２回服用すると、従来薬よりも３５％、脳卒中や全身性塞栓症の発症が減る。

　１９５０年代から使われているワーファリンは、心房細動後の脳卒中予防のほか、人工関節や人工心臓弁の装着など血栓ができやすい手術の後に欠かせないが、血液中の凝固成分を増やすビタミンＫの作用を抑える薬なので、納豆やクロレラなどビタミンＫを豊富に含む食品は禁忌だった。

（2011年1月23日 読売新聞）

B イレッサ被害「防げたはず」 : 医療ニュース : yomiDr./ヨミドクター(読売新聞)

リンク: イレッサ被害「防げたはず」 : 医療ニュース : yomiDr./ヨミドクター(読売新聞).

ちょうど昨日（1月19日），東京駅でイレッサ関連の抗議行動をみかけました。また，ちょうど昨日はテレビでも，海外で使用されている新薬承認の省略化に関する番組がくまれていました。いろいろと難しい問題が含まれています。

（以下引用）
元薬系技官トップが厚労省批判
　肺がん治療薬イレッサ（一般名ゲフィチニブ）の副作用で死亡した患者の遺族らが国とアストラゼネカ社に損害賠償を求めた訴訟で、東京・大阪両地裁が被告の救済責任を認め和解を勧告したことについて、旧厚生省の薬系技官トップだった土井脩氏（６７）が読売新聞の取材に応じ、イレッサを巡る厚生労働省の審査・安全対策の問題点を指摘し、早期解決を求めた。

　薬務行政の元責任者が古巣の施策を批判するのは異例で、波紋を広げそうだ。

　土井氏は、イレッサ問題が起きる前年の２００１年１月まで、医薬安全担当審議官を務めた。１９９３年、抗ウイルス剤ソリブジンと抗がん剤を併用した患者が死亡した薬害の発生当時は、安全対策の担当課長だった。

　イレッサは０２年７月、世界に先駆けて日本で承認されたが、まもなく間質性肺炎の副作用で死亡例が次々に報告された。土井氏は「最初に承認したのはよいが、前後の対応が問題。行政がやるべきことをやっていれば被害はかなり防げたはず」と話す。間質性肺炎については審査で指摘され、薬の添付文書にも盛り込まれたが、目立たない記載で現場に浸透しなかった上、その後の安全対策にも問題があった、という。

　まず承認の際、条件として全例調査を義務づけなかったのを「間違い」と言う。全例調査は、懸念のある薬の場合、使える医師を限定し、すべての投与患者を把握して、承認後も安全監視を続ける仕組み。土井氏は「イレッサにはこの条件が付かず、無防備に使用が拡大した」と指摘する。

　事後の対策では、「重大な副作用報告があったら迅速に対応すべきだ。イレッサの場合、緊急安全性情報を出して現場に注意喚起するまで３か月もかかった」と問題視する。ソリブジン薬害では、報告１週間後に緊急安全性情報が出た。

　厚労省は、今回の裁判で国の責任を認めると、薬の審査を慎重にせざるを得なくなり、抗がん剤などの承認が難しくなるとの懸念を示している。

　土井氏は「国があつものに懲りてなますを吹く対応をせず、懸念材料があれば条件つきで承認し、責任を持って審査から市販後まで一貫した安全対策を強化すれば、そんな問題は起きない」と断言。「裁判で無駄な時間を費やすより、患者の立場に立った対策に力を尽くすべきだ」と語った。

　地裁和解勧告でも土井氏同様の所見

　イレッサ訴訟で東京地裁が７日に示した和解勧告では、土井氏の指摘通り、ソリブジン薬害の教訓が生かされなかったことを問題視する所見が示されていた。

　イレッサの添付文書では、間質性肺炎についての記載が「重大な副作用」を示す欄の４番目と、目立たない扱いだった。ソリブジンもイレッサ同様、添付文書の記載が医療現場で見落とされ、被害につながった。ソリブジン薬害を契機に、重要な事項は前に記すよう添付文書の記載要領が改められたが、イレッサで同じ過ちが繰り返された。

　所見はソリブジン薬害に触れた上で、「（イレッサでも）重大な副作用欄の初めに記載したうえ、致死的なものとなりうることについて記載する行政指導を行うことが適切であった」などと指摘した。和解勧告への回答期限は今月２８日。原告は受け入れを表明したが、被告は国、アストラゼネカ社とも態度を保留している。

（2011年1月19日 読売新聞）

G 抗がん剤の最大の欠点カプセルで克服…東大開発 : 科学 : YOMIURI ONLINE（読売新聞）

リンク: 抗がん剤の最大の欠点カプセルで克服…東大開発 : 科学 : YOMIURI ONLINE（読売新聞）.

（以下引用）

人体が医薬品を異物として解毒したり、がん細胞が抗がん剤を排出したりする防御網をかいくぐり、抗がん剤をがん細胞の奥まで運べる微細カプセルの開発に、東京大などが成功した。

　効率的ながん治療を可能にする成果で、米医学誌サイエンス・トランスレーショナル・メディシンに６日発表する。

　カプセルの大きさは、ウイルスとほぼ同じ直径１０万分の４ミリ・メートル。表面が水になじむよう素材を工夫し、血液中にまぎれさせて人体の免疫機能に捕捉されないようにした。また、薬剤耐性を獲得したがん細胞は少ない分子からなる抗がん剤を外へ排出するポンプのような構造を持つため、細胞が取り込む栄養分に見せかけるよう、分子の数が多いカプセルを設計した。

　その結果、カプセルはがん細胞の遺伝子が収納された核の近くまで届いて初めて破壊されるようになり、抗がん剤が遺伝子の働きを邪魔してがん細胞の増殖を抑制できるようになった。

　開発した片岡一則教授は「カプセルは『トロイの木馬』のように、がん細胞に気付かれず入り込める。様々なタイプの抗がん剤が利用できるので、治療の幅が大きく広がる」と話している。

G Placebo effect: Placebos work, even when patients know they're phony - latimes.com

リンク: Placebo effect: Placebos work, even when patients know they're phony - latimes.com.

A simple sugar pill may help treat a disease — even if patients know they're getting fake medicine.

The finding, reported online Wednesday in the journal PloS One, may point the way to wider — and more ethical — applications of the well-known "placebo effect."

"The conventional wisdom is you need to make a patient think they're taking a drug; you have to use deception and lies," said lead author Ted Kaptchuk, an associate professor of medicine at Harvard Medical School. And, Kaptchuk added, it seems many doctors do this: In one report, as many as half of rheumatologists and internists surveyed said they had intentionally given patients ineffective medication in the hopes it would have a positive result.

Kaptchuk, however, wondered whether the deception was needed. When he first tried to persuade fellow researchers to explore a sort of "honest" placebo, "they said it was nuts," he said. After all, didn't the whole effect hinge on people believing they were getting real treatment?

Patients were easier to enlist. "People said, 'Wow, that's weird,' and we said, 'Yeah, we think it might work.' "

The researchers enrolled 80 people suffering from irritable bowel syndrome, explaining the experiment while framing it positively — they called it a novel "mind-body" therapy.

Half the patients were given a bottle with the word "placebo" printed on it. The pills it held, they were told, were like sugar pills. The patients were told they didn't even need to believe in the placebo effect, but had to take the pills twice daily.

The other half were given no treatment at all.

At the end of the three-week trial, 59% of the patients taking the placebo said their symptoms had been adequately relieved, far outstripping the 35% in the non-treatment group.

"We were all taken aback," Kaptchuk said. "We triple-checked the data before we decided it was real."

The results, which Kaptchuk said need to be replicated in a longer, larger study, show that placebo pills could be useful for chronic pain, depression and anxiety, among other ailments, without the need for deception.

"My personal hypothesis is this would not happen without a positive doctor-patient relationship," Kaptchuk said.

Others agreed.

"What seems to be the active ingredient is the warm, personal relationship," said Dr. Howard Brody of the University of Texas Medical Branch in Galveston.

Tor Wager, a cognitive neuroscientist at the University of Colorado at Boulder, said this and future research may help change the way doctors treat their patients.

"In terms of medical research, there's been a big gap between what people feel is true in the clinic and what is scientifically investigated," he said. "This study takes a step toward filling that gap. It shows the human context essentially does matter."

B オピオイド使用で有害事象が増える：Study Shows Higher Risks for Opioid Pain Drugs - WSJ.com

リンク: Study Shows Higher Risks for Opioid Pain Drugs - WSJ.com.

関節炎の痛みを緩和するために安易にオピオイドを使うと，かえって有害事象が増大するという記事です。米国と異なり日本では，それほど簡単にオピオイドは使われていません。

Arthritis patients taking opioid pain drugs had a higher risk of bone fractures and death compared with people taking other painkillers, according to a study that looked at Medicare claims records.

Researchers from Harvard-affiliate Brigham and Women's Hospital in Boston looked at painkiller use among Medicare beneficiaries over seven years, and found elevated risks from opioids, compared with other painkilling medications.

Other pain drugs compared included older ones like ibuprofen, Advil and Motril known as nonsteroidal anti-inflammatory drugs, or NSAIDs. Also compared were newer pain drugs, called "coxibs," like Celebrex and Vioxx, which has been withdrawn from the market.

Researchers focused on opioids because they have garnered relatively limited attention during the focus on other painkillers in recent years.

The study found that opioids were linked to an 87% increased risk of death during the study, compared to NSAIDs like ibuprofen. The coxib drugs didn't raise the risk of death. The study focused on 12,840 patients in Pennsylvania and New Jersey treated between January 1999 and December 2005.

The opioid drugs were linked to a 68% increase in overall "safety events"—ranging from intestinal bleeding to stroke and heart attack to fractures—when compared with the older painkillers. Newer pain drugs didn't show any increase in these overall safety events.

Perhaps most striking, the opioids were linked to a risk of fractures that was 4.5 times that in patients taking the NSAID drugs. Opioids include codeine, hydrocodone, oxycodone, propoxyphene and tramadol. But the risks weren't consistent among these. A second study by the same researchers found that the risk of death from any cause was 2.4 times as likely among those taking oxycodone, and twice as likely with those taking codeine, compared to those taking hydrocodone. Both studies are published in Monday's Archives of Internal Medicine.

Researchers noted that while the records examined showed "strong associations" between certain drugs and safety events, such an analysis of Medicare claims records "cannot prove causation."

G アスピリンの日常服用でがん予防：BBC News - Small daily aspirin dose 'cuts cancer risk'

リンク: BBC News - Small daily aspirin dose 'cuts cancer risk'.

少量のアスピリンを毎日服用することで，がん発症を防止できる。患者はアスピリン服用に伴う有害作用を上回る利益を得ることができる。

A small daily dose of aspirin - 75mg - substantially reduces death rates from a range of common cancers, a study suggests.

Research at Oxford University and other centres found that it cut overall cancer deaths by at least a fifth.

The study, published in the Lancet, covered some 25,000 patients, mostly from the UK.

Experts say the findings show aspirin's benefits often outweighed its associated risk of causing bleeding.

Aspirin is already known to cut the risk of heart attack and stroke among those at increased risk. But the protective effects against cardiovascular disease are thought to be small for healthy adults, and aspirin increases the risks of stomach and gut bleeds.

However, this latest research shows that when weighing up the risks and benefits of taking aspirin, experts should also consider its protective effect against cancer.

Those patients who were given aspirin had a 25% lower risk of death from cancer during the trial period and a 10% reduction in death from any cause compared to patients who were not given the drug.

Lasting protection

The treatment with aspirin lasted for between four and eight years, but long term-follow-up of around 12,500 patients showed the protective effect continued for 20 years in both men and women.

Lead researcher Professor Peter Rothwell said the findings might well underestimate the reduction in deaths that would result from longer-term treatment with aspirin.

The risk of cancer death was reduced by 20% over 20 years. For individual cancers the reduction was about 40% for bowel cancer, 30% for lung cancer, 10% for prostate cancer and 60% for oesophageal cancer.

The reductions in pancreas, stomach and brain cancers were difficult to quantify because of smaller numbers of deaths.

There was also not enough data to show an effect on breast or ovarian cancer and the authors suggest this is because there were not enough women in the trials. Large-scale studies investigating the effects on these cancers are under way.

Professor Rothwell said he was not urging healthy middle-aged adults to immediately start taking aspirin, but said the evidence on cancer "tips things towards it being well worth it". The benefit in cancer reduction were found from a low daily dose of 75mg.

Professor Rothwell said the annual risk of major internal bleeding was about 1 in 1,000 and aspirin roughly doubled that risk. But he said the danger of major bleeding was "very low" in middle age but increased dramatically after 75.

A sensible time to consider starting daily aspirin use would be between 45-50, continuing for around 25 years, he said.

Cancer Research UK described the results as "promising". But Ed Yong, head of health information and evidence, said: "We encourage anyone interested in taking aspirin on a regular basis to talk to their GP first."

Professor Peter Elwood, an epidemiologist from Cardiff University, who carried out some of the first studies into the effects of aspirin on health, said individuals should make up their own minds:

"Aspirin should be thought of in the same context as lifestyle changes such as diet and exercise which can help to preserve health."

Professor Elwood said taking aspirin at night and with calcium seemed to enhance its effects. He suggested taking it with a glass of milk as this could also reduce stomach irritation.

サリドマイド，骨髄腫治療薬として製造販売承認へ

●サリドマイドの国内製造販売承認へ。

●サリドマイドは近年，血液のがんである骨髄腫の治療薬として個人輸入により使用されていた。患者団体などから，骨髄腫としての製造販売が求められていた。

●サリドマイドは1950年代に睡眠薬として発売されたが，妊婦の服用による催奇性が問題となった。

●サリドマイドにはがん治療薬としての効果は少ないという意見もあるようだが，再発性・難治性の多発性骨髄腫患者にとっては，待望の承認である。

リンク: サリドマイド、骨髄腫治療薬として製造販売承認へ : 科学 : YOMIURI ONLINE（読売新聞）.

●以下引用。「厚生労働省は１８日、胎児の四肢などに深刻な障害を生んだ催眠鎮静剤サリドマイドを、血液がんの一種、多発性骨髄腫の治療薬として製造販売を承認する方針を決めた。

　年内にも国内企業による販売が再開される見通しだ。

　同日の有識者検討会で、原則として妊婦の服用を避けるため、〈１〉承認を申請した藤本製薬（大阪府松原市）が患者、医師、薬剤師を登録し、処方量や服用量を管理する〈２〉妊娠の可能性がある患者には処方前に妊娠の有無を検査する〈３〉飲み残さず、不要になったら返却する――などの必要事項を決めた。

　これらが守られていることを監視するため、厚労省や専門家のほか、患者、サリドマイド被害者の代表で構成する第三者評価委員会をつくり、違反があれば処方を中止させる。評価委の運営は国が財政支援し、薬害防止に厚労省が大きく関与する。

　厚労省は承認後、準備が整った病院から段階的に処方を認める方針。保険の適用対象は、推定１万３０００～１万４０００人の患者のうち再発性・難治性の患者で、治療薬の選択肢が広がることになる。

　多発性骨髄腫に対するサリドマイドの有効性は１９９０年代後半に報告され、海外１７か国で承認済み。国内では２０００年ごろから医師が未承認のまま推定８００人の患者に処方している。

　サリドマイドは鎮痛剤や胃腸薬として１９５８年に国内で発売され、つわり止めに使った妊婦の胎児に障害が相次いだ。認定被害者は３０９人に上り、６２年に販売が中止された。

（2008年9月18日20時26分  読売新聞）」