Murray J.Favus,M.D: Bisphosphonates for Osteoporosis. N Eng J MED 363;2027-35, 2010.


【The clinical problem】
Estrogen deficiency after menopause is the most common cause of osteoporosis, but secondary causes must be ruled out before treatment is undertaken.
Common Secondary Causes of Osteoporosis are Vitamin D deficiency, Primary hyperparathyroidism, Celiac disease, Idiopathic hypercalciuria, Hyperthyroidism, Myeloma.
Osteoporotic hip fractures are associated with the highest morbidity and mortality. Up to 50% of patients with such fractures have permanently impaired mobility, and 25% lose the skills necessary to live independently. The rate of death from any cause is increased by a factor of 5 to 8 during the first 3 months after a hip fracture.
Estrogen deficiency due to either spontaneous or surgical menopause activates osteoclast and accelerate bone resorption. Bisphosphonates disrupt the attachment of osteoclasts to the bone surface, and stop bone resorption.
【Clinical Evidence】
Alendronate and risedronate and zoledronic acid are effective to prevent hip fracture and vertebral fracture.
 Etidronate is effecitive to prevent vertebral fracture, but there is no study to show efficacy for the
treatment of hip fracture.
 Randomized, placebo-controlled trial of pamidronate has not been performed with sufficient power to assess the efficacy of the drug for the treatment of hip fracture in women with postmenopausal osteoporosis.
【Clinical use】
All postmenopausal women with measurements of bone mineral density at either the spine or the hip that meet World Health Organization (WHO) criteria for osteoporosis (T score of less than −2.5) should receive long-term therapy with an agent that has been proven to prevent fractures.
This author often uses the WHO Fracture Risk Assessment Tool (http://www.sheffield.ac.uk/FRAX/tool.jsp?lang=jp) to assist in making treatment decisions. FRAX is a calculator algorithm that incorporates risk factors with measurements of bone mineral density, generating a quantitative estimate of the 10-year probability of a major osteoporotic
fracture (hip, vertebral, humerus, or fore-arm) or of a hip fracture alone in patients who have not yet begun therapy. In general, the author initiates pharmacologic treatment in patients who have a 10-year probability of a hip fracture that exceeds 3% or a 10-year probability of a major osteoporotic fracture that exceeds 20%.
Raloxifene decreases the risk of vertebral fractures, but it may not reduce the risk of nonvertebral fractures.
Calcitonin has limited efficacy in reducing the risk of vertebral fractures and lacks efficacy in preventing hip fracture.
After initiating bisphosphonate therapy, this author typically reevaluate the patient in 1 month to assess tolerance and thereafter at 3 months, 6 months,and 1 year. At 3 months and 6 months, he obtain measurements of bone-turnover markers, such as osteocalcin or serum C-terminal telopeptide of type 1 collagen (CTX). At 1 year, and every 2 years thereafter, he repeat the assessment of bone mineral density with the use of DXA.
【Adverse effects】
 Erosive esophagitis, ulceration, and bleeding, heartburn, chest pain, hoarseness, and vocal-cord irritation, transient renal toxic effects, osteonecrosis of the jaw, etc.
【Areas of uncertainty】
  The optimal duration of bisphosphonate therapy remains uncertain. Recent retrospective studies and case reports suggest that long-term bisphosphonate therapy may result in the suppression of bone turnover and confer a predisposition to increased bone fragility, with an increased risk for atypical femur fractures. After 5 years of treatment, this author would decide whether a drug holiday might be appropriate for this patient, taking into consideration the fact that she is at high risk for recurrent fracture.

Areas of uncertaintyの項ではビスフォスフォネート製剤の長期的な使用がコツの脆弱性を引き起こす可能性を示唆するレトロスペクティブな研究と、この薬剤による治療の期間について言及している。




Joseph J. Y. Sung, et.al: Continuation of Low-Dose Aspirin Therapy in Peptic Ulcer Bleeding: A Randomized Trial. Annals of Internal Medicine: 152:1-9, 2010

Background: It is uncertain whether aspirin therapy should be continued after endoscopic hemostatic therapy in patients who develop peptic ulcer bleeding while receiving low-dose aspirin.

Objective: To test that continuing aspirin therapy with proton-pump inhibitors after endoscopic control of ulcer bleeding was not inferior to stopping aspirin therapy, in terms of recurrent ulcer bleeding in adults with cardiovascular or cerebrovascular diseases.

Design: A parallel randomized, placebo-controlled noninferiority trial, in which both patients and clinicians were blinded to treatment assignment, was conducted from 2003 to 2006 by using computer-generated numbers in concealed envelopes. (ClinicalTrials.gov registration number: NCT00153725)
Setting: A tertiary endoscopy center.

Patients: Low-dose aspirin recipients with peptic ulcer bleeding.
Their indication for aspirin is cardiovascular diseases or/and cerebrovascular diseases.

Intervention: 78 patients received aspirin, 80 mg/d, and 78 received placebo for 8 weeks immediately after endoscopic therapy. All patients received a 72-hour infusion of pantoprazole followed by oral pantoprazole. All patients completed follow-up.

Measurements: The primary end point was recurrent ulcer bleeding within 30 days confirmed by endoscopy. Secondary end points were all-cause and specific-cause mortality in 8 weeks.

Results: 156 patients were included in an intention-to-treat analysis. Three patients withdrew from the trial before finishing follow-up. Recurrent ulcer bleeding within 30 days was 10.3% in the aspirin group and 5.4% in the placebo group (difference, 4.9 percentage points [95% CI, −3.6 to 13.4 percentage points]). Patients who received aspirin had lower all-cause mortality rates than patients who received placebo (1.3% vs. 12.9%; difference, 11.6 percentage points [CI, 3.7 to 19.5 percentage points]). Patients in the aspirin group had lower mortality rates attributable to cardiovascular, cerebrovascular, or gastrointestinal complications than patients in the placebo group (1.3% vs. 10.3%; difference, 9 percentage points [CI, 1.7 to 16.3 percentage points]).

Limitations: The sample size is relatively small, and only low-dose aspirin, 80 mg, was used. Two patients with recurrent bleeding in the placebo group did not have further endoscopy.

Conclusion: Among low-dose aspirin recipients who had peptic ulcer bleeding, continuous aspirin therapy may increase the risk for recurrent bleeding but potentially reduces mortality rates. Larger trials are needed to confirm these findings.




Philip Castle: Recommendations for the use of human papillomavirus vaccines. UpToDate ONLINE 18.3: 2010. 
今野良:HPVワクチンによる子宮頚がん予防.JIM:p258、vol.20 No.4 2010

【Up to Date】より
初交以前のワクチン接種- 臨床試験の結果から、HPVワクチンはHPV未感染の人たちに最も有効である。(初交以前など) なぜならHPVワクチンは予防であり、治療ではないので、すでに感染している16型または18型のHPVが発症することを防ぐことは出来ない。ワクチンを行えば、これらのタイプのHPVに対する保護的な免疫ができる。アメリカ合衆国では9歳から26歳の間の全ての女性にHPVワクチンが推奨されている。

費用対効果 ― HPVワクチンの費用対効果が複数の研究において数学的に検証された。ある研究では、米国12歳の女児全員に接種することで、20万以上のHPVの感染を予防し、10万以上の頸部細胞診の異常を予防し、近年の推奨通りに頸部がん検診を継続すれば3300例の子宮頸癌を予防すると示している。ワクチン接種年齢が増すにつれ費用対効果は低下していく。HPVワクチンが終生免疫と仮定すると、12歳の少女にワクチン接種した場合、費用対効果は1QALY(quality-adjusted life-year)あたり$43,600という報告がある一方、別の報告では26歳まで範囲を拡大して予防接種を行った場合は1QALYあたり$152,700まで上昇する。




感染者の90%はHPVは2年以内に消失している。日本においては、10代後半や20代前半では50%の感染率であるが、40歳代 以降になると5~10%である。





~Effectiveness of screening for CKD(CKDのスクリーニングの有効性)~


Braden Manns, et.al.:  Population based screening for chronic kidney disease: cost effectiveness study.BMJ 341:5869,2010.


To determine the cost effectiveness of one-off population based screening for chronic kidney disease based on e-GFR. 


Cost utility analysis of screening with e-GFR alone compared with no screening. Analyses were stratified by age, diabetes, and the presence or absence of proteinuria. 
Scenario and sensitivity analyses, including probabilistic sensitivity analysis, were performed. Costs were estimated in all adults and in subgroups defined by age, diabetes, and hypertension. 


Publicly funded Canadian healthcare system. 


Large population based laboratory cohort used to estimate mortality rates and incidence of end stage renal disease for patients with chronic kidney disease over a five year follow-up period. Patients had not previously undergone assessment of GFR. 

【Main outcome measures】

Lifetime costs, end stage renal disease, quality adjusted life years (QALYs) gained, and incremental cost per QALY gained. 


Compared with no screening, population based screening for chronic kidney disease was associated with an incremental cost of $C463 (Canadian dollars in 2009; equivalent to about £275, €308, US $382) and a gain of 0.0044 QALYs per patient overall, representing a cost per QALY gained of $C104 900. 
In a cohort of 100 000 people, screening for chronic kidney disease would be expected to reduce the number of people who develop end stage renal disease over their lifetime from 675 to 657.
In subgroups of people with and without diabetes, the cost per QALY gained was $C22 600 and $C572 000, respectively. In a cohort of 100 000 people with diabetes, screening would be expected to reduce the number of people who develop end stage renal disease over their lifetime from 1796 to 1741. 
In people without diabetes with and without hypertension, the cost per QALY gained was $C334 000 and $C1 411 100, respectively.


Population based screening for chronic kidney disease with assessment of e-GRF is not cost effective overall or in subgroups of people with hypertension or older people.
 Targeted screening of people with diabetes is associated with a cost per QALY that is similar to that accepted in other interventions funded by public healthcare systems.




Donald A. Redelmeier, Robert B. Cialdini. Problems for clinical judgement: 5. Principles of influence in medical practice. CMAJ 2002;166(13):1680-1684

医療における「影響力」の7要素-人はなぜ動かされるのか?- 広島大学病院 佐伯俊成


心理学における基礎科学は特異的な自動反応(ingrained responses=しみついた反応)を同定した。その反応というのは人の性質の根本的な要素であり、一般的な影響の戦略(influence strategies)を裏打ちするもので、医療の現場において適応できるかもしれない。・人は受けた恩義にこたえようとする義務感を感じる。・少しばかり受け入れがたいお願いを先にすると、(それより条件の良い)要求はより魅力的になる。・一貫性のある活動への意欲というのはたとえ要求が過剰になっても続く。・人は不確実な状態に直面した時、周囲からの圧力(Peer Pressure)は極めて強いものとなる。・要求する人のイメージが要求それ自体の魅力に影響を与える。・権威は専門家としての力量以上の力を持っている。・機会はそれらが得られにくように見える時ほど、より価値あるように見える。これらの7つの反応は何十年も前に心理学の研究により発見され、ビジネスの世界で直観的に理解されているようであるが、医療の文脈ではめったに議論がされていない。臨床家はこれらの原理を意識することで、患者が自分の行動を変える手助けをし、社会における他の人々が時に患者の選択をどの様に変えるのかということを理解するための、一つのフレームワークを提供することが出来る。

【Basic theory:基本的原理】

患者は圧倒的な情報の中で生活しているので、たとえ関係のある出来ごとでも「思慮深い決断」を下すことはほぼ不可能である。これらをうまく処理するためには、患者は自動反応(ingrained responses)と呼ばれる理にかなった近道が頼りになる。人の論理的思考過程において、自動反応というのは大半の影響の戦略の根底にある基本的な経路である。これらの経路を意識することが、患者が習慣を変える手助けを試みるためのフレームワークを臨床家に提供する。(Table1)



























臨床家は助言をより強力な物にするため希少性を思い起こさせるかもしれない。前置きのアドバイスにて「今日見た全ての患者の中であなたが一番心に残っています、なぜなら…」 このような差別化は、この後にどの様なアドバイスが来たとしても重みを与え、彼らの習慣を変えるよう動機づけられるかもしれない。色々な代替案を示されるより、一つの選択肢をしめされたとき、そのままの状態を差し控え、新たな選択を受け入れる傾向になぜあるかということを、この希少性の原理は説明する助けになる。特別な治療を受けているという認識が、なぜ心移植患者が従順であり続けるかということを説明しているかもしれない。


自由社会において有能な大人の習慣を変えるにはコントロールするのではなく影響力を行使することが必要である。医学の全ての側面にいえることだが、影響力の戦略は狙ったケアによって良いものにも害にもなり得る。社会における力(forces in society)が既にこれらのテクニックを患者に対して使用しているのが現実である。患者が有益な選択をする手助けをするにはどのようにするかを意識することが、効果的なケアを提供するために臨床家に必要なスキルである。




Givens JL, Jones RN, et al. Survival and Comfort After Treatment of Pneumonia in Advanced Dementia. Arch Intern Med 170 (13), 1107-9.








重度認知症の入居者で肺炎と確定診断された患者 Table1参照。




・Cognitive Performance Score 5^6点(重度の認知能低下)

・Global Deterioration Scale 7点(家族がわからない、最低限の会話、ADL全介助、便尿失禁)





快適さ(scored according to the Symptom Management at End-of-Life in Dementia scale:SM-EOLD)

測定前90日間の痛み・呼吸苦・抑うつ・恐れ・心配・いらいら・落ち着き・皮膚の損傷・介護への抵抗の項目に対して頻度(なし、月1回、月数回、週1回、週数回、毎日)を介護士?nursing caringが記載。点数が高いほど、快適度が高いスコア。

※90以内に亡くなった方は除外されるが、Comfort Assessment in Dying with Dementia scaleが死亡後2週間以内に測定された。







生命予後Table3/Figureは、治療しない人と比べて、すべての治療あり群は改善(経口群リスク比0.2 95%CI 0.10‐0.37)(筋注群リスク比0.26 95%CI 0.12‐0.57)(点滴・入院群リスク比0.2 95%CI 0.09‐0.42)であった。

快適さはTable4、治療前のSM-EOLDと比べ、いずれの抗菌薬治療をえた群でもscored according to the Symptom Management at End-of-Life in Dementia scaleは低かった。