― 文献名 ― 
 Thien-Giang Bach-Huynh, Bindu Nayak, Jennifer Loh, Steven Soldin, and Jacqueline Jonklaas

Timing of Levothyroxine Administration Affects Serum Thyrotropin Concentration
J Clin Endocrinol Metab. 2009 October; 94(10):905-3912.

― 要約 ―

Context: レボチロキシンは、食事による吸収阻害を防ぐため朝食前に内服されている。TSH濃度はレボチロキシンの効果の指標である。

Objective: レボチロキシンのTSH濃度に対する効果が、食事摂取と関連した内服のタイミングで変化するかを検討する
Design: 参加者はランダムに6つに振り分けられ、それぞれが8週間のレジメンを3ターム行うクロスオーバーデザインで実施される。3タームのレジメンはそれぞれ朝食前・就寝前・朝食時での内服。TSH・freeT4・freeT3濃度が各レジメンで測定される。
Primary outcomeは、他のレジメンと朝食前のレジメンとのTSH濃度の相違。

Setting: academic medical centerで実施された

Participants: 甲状腺機能低下症または甲状腺癌の治療のためレボチロキシンを内服している患者

Results: 65人の患者が参加。朝食前内服の平均TSH濃度は1.06 ± 1.23 mIU/L。朝食時内服の平均TSH濃度は有意に高かった(2.93 ± 3.29 mIU/L). 就寝前内服の平均TSH濃度もまた優位に高かった(2.19 ± 2.66 mIU/L)。

Conclusion: 朝食前以外のレジメンでは、TSH濃度が高く、またばらつきが大きかった。特定のTSHの目標値が望まれ、それにより医原性の潜在性甲状腺疾患を避けるならば、朝食前のレボチロキシン内服により最も狭い目標範囲でのTSH濃度が確保されるだろう。

― 考察とディスカッション ―




 Exercise Relieves Pain in Patients with Lower-Extremity Osteoarthritis
    2013 October 24 BMJ


 膝関節のOAを有する患者に関する試験が44件、股関節のOAを有する患者に関する試験が2件、膝関節、股関節、その他の関節のOAを有する患者に関する試験が12件であった。評価の対象とされた運動の種類は、強化運動、柔軟運動、有酸素運動、およびこれらの運動の水中バージョンであった。疼痛の軽減(視覚的な疼痛尺度[visual pain scales])によって測定)については、強化運動、強化運動と柔軟運動の併用、水中バージョン以外の併用(強化運動と柔軟運動と有酸素運動の併用)、水中での強化運動、水中での強化運動と柔軟運動の併用で、運動なしの場合よりも有意に高い効果がみられた。疼痛が軽減する確率がもっとも高かったのは、水中での強化運動と柔軟運動を併用した場合であり、その次に高かったのは、強化運動のみの場合であった。身体機能の改善については、強化運動、強化運動と柔軟運動の併用、水中バージョン以外の各運動の併用で、運動なしの場合よりも有意に高い効果がみられた。



― 文献名 ―

 Ketan Dhatariya. Uncertainties: Should inpatient hyperglycaemia be treated? BMJ 2013;346:f134 doi: 10.1136/bmj.f134

― この文献を選んだ背景 ―

 Usually, we try to control blood glucose of patients who are admitted with acute illness.
But after reading this article, I found that this is not confirmed with good evidence and realized the importance of knowing that some of our usual care may lack sufficient evidence.

― 要約 ―

   Two large scale randomised controlled trials in the 1990s were the first such trials to show that the control of blood glucose helped to prevent long term complications in people with types 1 and 2 diabetes.1 2 Glucose concentrations can rise not only in people with pre-existing diabetes, but also, for short periods, in people without the condition–in particular, during times of acute illness, when it is called stress hyperglycaemia.3
 Data show that raised blood glucose concentrations in people with and without a previous diagnosis of diabetes are associated with short term harm. However, whereas the benefits of good glycaemic control over a long period in people with diabetes are well established, uncertainty remains about whether treating transient hyperglycaemia, in particular in hospital inpatients, makes any difference to short term outcomes.

What is the evidence of the uncertainty?
   Since the two trials in the 1990s,1 2 other studies have also shown that hyperglycaemia in inpatients with and without pre-existing diabetes is associated with poor outcomes. However, most trials were observational, with only a few randomised controlled trials. A meta-analysis of 34 randomised control trials assessing perioperative insulin infusion in 2192 surgical patients concluded that “perioperative insulin infusion may reduce mortality but increases hypoglycaemia in patients who are undergoing surgery.”5 However, only 14 of these studies included patients with diabetes, with 13 studies
excluding them and the rest not reporting whether patients with diabetes were included.

   Observational data from an unselected cohort of over 1500 acute general medical admissions with and without diabetes showed that length of stay, readmission rates, and 30 day mortality rates rose with higher blood glucose concentrations.6 Other observational evidence from hospital episode statistics based on discharge coding of over four million patients showed that those who also had diabetes stayed in hospital the longest, regardless of the specialty.7

   People with stress hyperglycaemia may be at risk of developing type 2 diabetes in the long term. However, evidence from intervention studies is sparse or conflicting on whether aggressive treatment of the hyperglycaemia during a patient’s hospital stay makes a difference to short or long term outcomes or even affects outcomes related to their cause for admission. Indeed, data from well conducted large randomised controlled trials and observational studies show that the use of glucose lowering agents–in particular, insulin–are associated with increased levels of harm, in the form of severe hypoglycaemia.10 11

   A few randomised controlled trials show that short term, tight glycaemic control using insulin therapy in intensive care seemed to reduce mortality, infection rate, and length of hospital stay.12 13 Other well conducted randomised controlled trials in intensive care patients have been either equivocal14 15 or associated with harm, with the largest such study of over 6000 patients showing that tight glycaemic control was associated with higher incidence of severe hypoglycaemia and increased mortality.16

   There are good theoretical reasons why glucose reduction with insulin should be beneficial, with reductions in endothelial dysfunction, immune dysfunction, and the maintenance of adequate vasodilatation.20 But insulin use in any patient with hyperglycaemia is fraught with problems and is often used incorrectly or ineffectively–the use of subcutaneous “sliding scales” being one such problem.21 Precipitating severe hypoglycaemia by aggressive glucose lowering with insulin is a major concern.
Uncertainty also remains about the glucose targets that should be aimed for and the best agents to achieve these.

   The data presented show that high glucose concentration in people with and without diabetes is associated with poor outcomes. However, as the author found no directly relevant systematic reviews it remains to be determined if the raised blood glucose is the cause of the poor outcomes or if it is just an epiphenomenon.

What should we do in the light of the uncertainty?
   If the patients are found to be hyperglycaemic then efforts should be made to control their glucose concentrations on the basis of pragmatic consensus documents drawing largely on the best available observational data previously described. 



– 文献名 –

Michael A. Becker, M.D., H. Ralph Schumacher, Jr., M.D., Robert L. Wortmann, M.D., Patricia A. MacDonald, B.S.N., N.P., Denise Eustace, B.A., William A. Palo, M.S., Janet Streit, M.S., and Nancy Joseph-Ridge, M.D., Febuxostat Compared with Allopurinol in Patients with Hyperuricemia and Gout, New England Journal Medicine 2005; 353:2450-2461

– 要約 –

Febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase, is a potential alternative to allopurinol for patients with hyperuricemia and gout.

We randomly assigned 762 patients with gout and with serum urate concentrations of at least 8.0 mg per deciliter (480 μmol per liter) to receive either febuxostat (80 mg or 120 mg) or allopurinol (300 mg) once daily for 52 weeks; 760 received the study drug. Prophylaxis against gout flares with naproxen or colchicine was provided during weeks 1 through 8. The primary end point was a serum urate concentration of less than 6.0 mg per deciliter (360 μmol per liter) at the last three monthly measurements. The secondary end points included reduction in the incidence of gout flares and in tophus area.

The primary end point was reached in 53 percent of patients receiving 80 mg of febuxostat, 62 percent of those receiving 120 mg of febuxostat, and 21 percent of those receiving allopurinol (P<0.001 for the comparison of each febuxostat group with the allopurinol group). Although the incidence of gout flares diminished with continued treatment, the overall incidence during weeks 9 through 52 was similar in all groups: 64 percent of patients receiving 80 mg of febuxostat, 70 percent of those receiving 120 mg of febuxostat, and 64 percent of those receiving allopurinol (P=0.99 for 80 mg of febuxostat vs. allopurinol; P=0.23 for 120 mg of febuxostat vs. allopurinol). The median reduction in tophus area was 83 percent in patients receiving 80 mg of febuxostat and 66 percent in those receiving 120 mg of febuxostat, as compared with 50 percent in those receiving allopurinol (P=0.08 for 80 mg of febuxostat vs. allopurinol; P=0.16 for 120 mg of febuxostat vs. allopurinol). More patients in the high-dose febuxostat group than in the allopurinol group (P=0.003) or the low-dose febuxostat group discontinued the study. Four of the 507 patients in the two febuxostat groups (0.8 percent) and none of the 253 patients in the allopurinol group died; all deaths were from causes that the investigators (while still blinded to treatment) judged to be unrelated to the study drugs (P=0.31 for the comparison between the combined febuxostat groups and the allopurinol group). CONCLUSIONS Febuxostat, at a daily dose of 80 mg or 120 mg, was more effective than allopurinol at the commonly used fixed daily dose of 300 mg in lowering serum urate. Similar reductions in gout flares and tophus area occurred in all treatment groups. 開催日:平成25年9月4日

咳はどのくらいつづくのか? システマティック・レビューのデータと患者の予測の比較

- 文献名 -

 Mark H. Ebell, MD, MS, Jerold Lundgren, BS and Surasak Youngpairoj, MD, MPH. How long does a cough last? Comparing patients’ expectations with data from a systematic review of the literature. Annals of Family Medicine. 2013 Jan-Feb; 11(1):5-13.

- この文献を選んだ背景 -


- 要約 -
 acute cough illness(ACI)に対する抗生剤乱用の原因のひとつに、ACIの自然経過と患者の予測との間の相違があるのではないか、と仮説を立て検証した。

    ■咳は3種類(黄色痰、緑色痰、乾性咳) / 発熱ある・なし

 文献によると咳症状の平均持続期間は17.8日間であった。電話調査の回答の中央値は5-7日間、平均持続期間は7.2-9.3日間であった(シナリオによって異なる)。白人、女性、自己申告で喘息あるいは慢性肺疾患に罹患していると答えた人は、症状持続期間を長めに回答する傾向があった。抗生剤が常に有用だと回答した人の独立予測因子は、有色人種(OR = 1.82, 95% CI, 1.14-2.92)、大卒以下(OR = 2.08, 95% CI, 1.26-3.45)、ACIに対する抗生剤使用歴(OR = 2.20, 95% CI, 1.34-3.55)であった。


- 考察とディスカッション -

 今回の研究の対象となった集団は、人種がちがうものの年齢層やセッティングなど現在働いているクリニックに比較的近いのではないかと感じた。患者のもつ風邪の期間に対する考え方も同じような印象をもった(たいてい1週間程経って治らないと受診する傾向にある。)私自身、風邪の治癒までの期間についてpost-infectious coughで長引くことはあるなと思いつつ、2-3週間咳が続く人には、抗生剤の処方こそしないが、結核や肺癌が心配になり、胸部Xpを撮ることがあった。ただ、この研究で咳症状のみを根拠にはしてはいけないと改めて反省した。
 また、家庭医療のコア・コンピテンシーであるPCCMにおいて、患者の持つillness expectationと臨床的事実の間のギャップを埋めるべく共通の理解基盤を構築していく過程があるが、そのバックグラウンドとして今回のようなmassな患者を対象としたillness expectationの調査は有用だと感じた。



 Uptodate [Anticoagulation in acute pulmonary embolism]

have some patients in home visit who are difficult to do blood test. Because
they have a fragile blood vessels and we can’t find thick and good ones. Some
patients take warfarin to prevent re-attack of pulmonary embolism, so we must
check INR every month.

wonder if it is necessary to check INR every month or it is possible to change
a drug except warfarin or stop it.

Monitoring — The
laboratory test most commonly used to measure the effects of warfarin is the INR. Warfarin therapy
for acute PE should target an INR of 2.5 (range 2.0 to 3.0) [5,40]. Randomized trials indicate
that less intense anticoagulation (INR <2.0) is associated with an increased
likelihood of recurrent PE or DVT and more intense anticoagulation is
associated with bleeding [40-44].

Following discharge, initial monitoring can be reduced to once every few days until a stable dose has been achieved [40] and then to once every four weeks [45]. INR measurements should return to the more frequent interval any time that adjustments in the dose become necessary and the more frequent interval should be continued until a stable dose is again achieved. (See “Therapeutic use of warfarin“.
Long-term therapy — After initial therapy with LMWH, UFH, or subcutaneous fondaparinux, long-term therapy is generally completed with a vitamin K antagonist, such as warfarin. Vitamin K antagonists are preferred over rivaroxaban due to the greater clinical experience with the former [5].
Duration — We advocate the following treatment durations for warfarin therapy. Recommendations for indefinite therapy ascribe a higher value to preventing recurrent PE and a lower value to bleeding, cost, and inconvenience.
•    For patients with a first episode of acute PE due to a temporary risk factor (eg, surgery, immobilization, trauma), we recommend warfarin therapy for three months, rather than a shorter or longer duration (Grade 1B). (See ‘Reversible risk factor’ above.)
•    For patients with a first episode of unprovoked acute PE, we recommend warfarin therapy for at least three months, rather than a shorter duration (Grade 1B). The potential benefits and risks of indefinite anticoagulant therapy should be assessed after the three months of anticoagulant therapy (see ‘Unprovoked’ above):
•    For patients who have a low or moderate risk of bleeding, we suggest indefinite warfarin therapy, rather than three months of therapy (Grade 2B).
•    For patients who have a high risk of bleeding, we recommend three months of warfarin therapy, rather than indefinite therapy (Grade 1B).
•    For patients with two or more episodes of acute PE, we recommend warfarin therapy for at least three months, rather than a shorter duration (Grade 1B). The potential benefits and risks of indefinite anticoagulant therapy should be assessed after the three months of anticoagulant therapy (see ‘Recurrent PE’ above):
•    For patients who have a low risk of bleeding, we recommend indefinite warfarin therapy, rather than three months of therapy (Grade 1A).
•    For patients who have a moderate risk of bleeding, we suggest indefinite warfarin therapy, rather than three months of therapy (Grade 2B).
•    For patients who have a high risk of bleeding, we suggest three months of warfarin therapy, rather than indefinite therapy (Grade 2B).
Anticoagulant therapy for
patients with an acute PE who are pregnant or have a malignancy is discussed



 Aleesa A Carter, Tara Gomes, Ximena Camacho, et al. Risk of incident diabetes among patients treated with statins: population based study.BMJ 2013; 346.







結果: プラバスタチン(全ての解析における対照薬剤)と比較して、アトロバスタチン(補整ハザード比 1.22, 95% C.I. 1.15 to 1.29)、ロスバスタチン(1.18, 1.10 to 1.26)、シンバスタチン(1.10, 1.04 to 1.17)では糖尿病の発症リスクが増加した。フルバスタチン(0.95, 0.81 to 1.11)やロバスタチン(0.99, 0.86 to 1.14)を投与された患者群では優位なリスクの増加はなかった。アトロバスタチンとロスバスタチンの糖尿病発症絶対リスクはそれぞれ31、34/1000人年だった。シンバスタチンのリスクはわずかに低く(26 /1000人年)、対照となったプラバスタチンは23/1000人年だった。この結果は、スタチンが心血管疾患の1次予防を目的として投与された場合と2次予防を目的として投与された場合とで変わらなかった。効力によりスタチンを分類した時も同じような結果となったが、投与量も考慮した際にはロスバスタチンによる糖尿病発症リスクは有意なものではなくなった (補整ハザード比 1.01, 0.94 to 1.09) 。



プライマリケアの現場での虚血性脳卒中リスク評価 QStroke scoreについて

– 文献名 -
 Derivation and validation of QStroke score for predicting risk of ischaemic stroke in primary care and comparison with other risk scores: a prospective open cohort study   Julia Hippisley-Cox , et al. BMJ 2013;346:f2573

- この文献を選んだ背景 -
 We usually examine the patients with stroke, hypertension, diabetes, atrial fibrillation, and so on. When we examine such as patients, we evaluate risk of ischemic stroke. For example,when we examine the patients with atrial fibrillation, we evaluate CHADS2 score and consider whether we should prescribe anticoagulants. 
I found this article about the predicting risk of ischemic stroke in primary care. I read it.

- 要約 -
 Objective :To develop and validate a risk algorithm (QStroke) to estimate risk of stroke or transient ischaemic attack in patients without prior stroke or transient ischaemic attack at baseline; to compare (a) QStroke with CHADS2 and CHA2DS2VASc scores in patients with atrial fibrillation and (b) the performance of QStroke with the Framingham stroke score in the full population free of stroke or transient ischaemic attack.
Design :Prospective open cohort study using routinely collected data from general practice during the study period 1 January 1998 to 1 August 2012.
Setting :451 general practices in England and Wales contributing to the national QResearch database to develop the algorithm and 225 different QResearch practices to validate the algorithm.
Participants :3.5 million patients aged 25-84 years with 24.8 million person years in the derivation cohort who experienced 77 578 stroke events. For the validation cohort, we identified 1.9 million patients aged 25-84 years with 12.7 million person years who experienced 38 404 stroke events. We excluded patients with a prior diagnosis of stroke or transient ischaemic attack and those prescribed oral anticoagulants at study entry.
Main outcome measures :Incident diagnosis of stroke or transient ischaemic attack recorded in general practice records or linked death certificates during follow-up.
Risk factors :Self assigned ethnicity, age, sex, smoking status, systolic blood pressure, ratio of total serum cholesterol to high density lipoprotein cholesterol concentrations, body mass index, family history of coronary heart disease in first degree relative under 60 years, Townsend deprivation score, treated hypertension, type 1 diabetes, type 2 diabetes, renal disease, rheumatoid arthritis, coronary heart disease, congestive cardiac failure, valvular heart disease, and atrial fibrillation
Results :The QStroke algorithm explained 57% of the variation in women and 55% in men without a prior stroke. The D statistic for QStroke was 2.4 in women and 2.3 in men. QStroke had improved performance on all measures of discrimination and calibration compared with the Framingham score in patients without a prior stroke. Among patients with atrial fibrillation, levels of discrimination were lower, but QStroke had some improved performance on all measures of discrimination compared with CHADS2 and CHA2DS2VASc.
Conclusion :QStroke provides a valid measure of absolute stroke risk in the general population of patients free of stroke or transient ischaemic attack as shown by its performance in a separate validation cohort. QStroke also shows some improvement on current risk scoring methods, CHADS2 and CHA2DS2VASc, for the subset of patients with atrial fibrillation for whom anticoagulation may be required. Further research is needed to evaluate the cost effectiveness of using these algorithms in primary care.




- 文献名 -
 Kidney stones and kidney function loss: a cohort study
 BMJ 2012; 345 doi: http://dx.doi.org/10.1136/bmj.e5287 (Published 30 August 2012)
R Todd Alexander, Brenda R Hemmelgarn,  Natasha Wiebe, Aminu Bello, Catherine Morgan, Susan Samuel,  Scott W Klarenbach, Gary C Curhan,  Marcello Tonelli,

- 要約 -

Objective To investigate whether the presence of kidney stones increase the risk of end stage renal disease (ESRD) or other adverse renal outcomes.
Design A registry cohort study using validated algorithms based on claims and facility utilisation data. Median follow-up of 11 years.
Setting Alberta, Canada, between 1997 and 2009.
Participants 3 089 194 adult patients without ESRD at baseline or a history of pyelonephritis. Of these, 1 954 836 had outpatient serum creatinine measurements and were included in analyses of chronic kidney disease and doubling of serum creatinine level.
Exposure One or more kidney stones during follow-up.
Main outcome measures Incident ESRD, development of stage 3b-5 chronic kidney disease (estimated glomerular filtration rate <45 mL/min/1.73 m2), and sustained doubling of serum creatinine concentration from baseline. Results 23 706 (0.8%) patients had at least one kidney stone, 5333 (0.2%) developed ESRD, 68 525 (4%) developed stage 3b-5 chronic kidney disease, and 6581 (0.3%) experienced sustained doubling of serum creatinine. Overall, one or more stone episodes during follow-up was associated with increased risk of ESRD (adjusted hazard ratio 2.16 (95% CI 1.79 to 2.62)), new stage 3b-5 chronic kidney disease (hazard ratio 1.74 (1.61 to 1.88)), and doubling of serum creatinine (hazard ratio 1.94 (1.56 to 2.43)), all compared with those without kidney stones during follow-up. The excess risk of adverse outcomes associated with at least one episode of stones seemed greater in women than in men, and in people aged <50 years than in those aged ≥50. However, the risks of all three adverse outcomes in those with at least one episode of stones were significantly higher than in those without stones in both sexes and age strata. The absolute increase in the rate of adverse renal outcomes associated with stones was small: the unadjusted rate of ESRD was 2.48 per million person days in people with one or more episodes of stones versus 0.52 per million person days in people without stones. Conclusion Even a single kidney stone episode during follow-up was associated with a significant increase in the likelihood of adverse renal outcomes including ESRD. However, the increases were small in absolute terms. 開催日:2012年11月28日


- 文献名 -
 M. SUE KIRKMAN et al. Diabetes in Older Adults. Diabetes Care online October 25, 2012

- この文献を選んだ背景 -

- 要約 -