カテゴリー: 臓器別の問題

【文献名】

Memantine Treatment in Patients With Moderate to Severe Alzheimer Disease Already Receiving Donepezil  A Randomized Controlled Trial　JAMA 2004 Jan 21;Vol291,No.3:317-324



【要約】

＜Context＞

Memantine is a low- to moderate-affinity, uncompetitive N-methyl-Daspartate receptor antagonist. Controlled trials have demonstrated the safety and efficacy of memantine monotherapy for patients with moderate to severe Alzheimer disease(AD) but no controlled trials of memantine in patients receiving a cholinesterase inhibitor have been performed.

Objective  To compare the efficacy and safety of memantine vs placebo in patients with moderate to severe AD already receiving stable treatment with donepezil.



＜Design, Setting, and Participants＞

A randomized, double-blind, placebo controlled clinical trial of 404 patients with moderate to severe AD and Mini-Mental State Examination scores of 5 to 14, who received stable doses of donepezil, conducted at 37 US sites between June 11, 2001, and June 3, 2002. A total of 322 patients (80%) completed the trial.



＜Interventions＞

Participants were randomized to receive memantine (starting dose 5 mg/d, increased to 20 mg/d, n=203) or placebo (n=201) for 24 weeks.



＜Main Outcome Measures＞

Change from baseline on the Severe Impairment Battery (SIB), a measure of cognition, and on a modified 19-item AD Cooperative Study? Activities of Daily Living Inventory (ADCS-ADL19). Secondary outcomes included a Clinician’s Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus), the Neuropsychiatric Inventory, and the Behavioral Rating Scale for Geriatric Patients (BGP Care Dependency Subscale).



＜Results＞

The change in total mean (SE) scores favored memantine vs placebo treatment for SIB (possible score range, 0-100), 0.9 (0.67) vs ?2.5 (0.69), respectively (P_.001); ADCS-ADL19 (possible score range, 0-54), ?2.0 (0.50) vs ?3.4 (0.51), respectively (P=.03); and the CIBIC-Plus (possible score range, 1-7), 4.41 (0.074) vs 4.66 (0.075), respectively (P=.03). All other secondary measures showed significant benefits of memantine treatment. Treatment discontinuations because of adverse events for memantine vs placebo were 15 (7.4%) vs 25 (12.4%), respectively.



＜Conclusions＞

In patients with moderate to severe AD receiving stable doses of donepezil, memantine resulted in significantly better outcomes than placebo on measures of cognition, activities of daily living, global outcome, and behavior and was well tolerated. These results, together with previous studies, suggest that memantine represents a new approach for the treatment of patients with moderate to severe AD.



【開催日】

2011年8月24日

【文献名】

Leslee L. Subak, M.D.,　 Weight Loss to Treat Urinary Incontinence　in Overweight and Obese Women　N Engl J Med 2009 360;5 jan 29, 481-490



【要約】

＜Background＞

Obesity is an established and modifiable risk factor for urinary incontinence, but conclusive evidence for a beneficial effect of weight loss on urinary incontinence is lacking.



＜Methods＞

Researchers randomly assigned 338 overweight and obese women with at least 10 urinary incontinence episodes per week to an intensive 6-month weight-loss program that included diet, exercise, and behavior modification (226 patients) or to a structured education program (112 patients).



＜Results＞

The mean (±SD) age of the participants was 53±11 years. The body-mass index (BMI) (the weight in kilograms divided by the square of the height in meters) and the weekly number of incontinence episodes as recorded in a 7-day diary of voiding were similar in the intervention group and the control group at baseline (BMI, 36±6and 36±5, respectively; incontinence episodes, 24±18 and 24±16, respectively). The women in the intervention group had a mean weight loss of 8.0% (7.8 kg), as compared with 1.6% (1.5 kg) in the control group (P<0.001). After 6 months, the mean weekly number of incontinence episodes decreased by 47% in the intervention group, as compared with 28% in the control group (P = 0.01). As compared with the control group, the intervention group had a greater decrease in the frequency of stress incontinence episodes (P = 0.02), but not of urge-incontinence episodes (P = 0.14).A higher proportion of the intervention group than of the control group had a clinically relevant reduction of 70% or more in the frequency of all incontinence episodes (P<0.001), stress-incontinence episodes (P = 0.009), and urge-incontinence episodes(P = 0.04).

 ＜Conclusions＞
 A 6-month behavioral intervention targeting weight loss reduced the frequency of self-reported urinary-incontinence episodes among overweight and obese women as compared with a control group. A decrease in urinary incontinence may be another benefit among the extensive health improvements associated with moderate weight reduction. 

 【開催日】
 2011年8月17日

【文献名】

Sertraline or mirtazapine for depression in dementia (HTA-SADD): a randomised, multicentre, double-blind, placebo-controlled trial. The Lancet, Volume 378, Issue 9789, Pages 403 – 411, 30 July 2011.



【要約】
うつ症状を示すアルツハイマー病患者に、選択的セロトニン再取り込み阻害薬（SSRI）のセルトラリン、ノルアドレナリン作動性・特異的セロトニン作動性抗うつ薬（NaSSA）のミルタザピン、偽薬のいずれかを投与した無作為化試験の結果が、Lancet誌2011年7月18日号に掲載された。英London King’s CollegeのSube Banerjee氏らによると、13週後と39週後のうつ症状の変化において、どちらの抗うつ薬にも偽薬を上回る利益は見られず、有害事象発生率は高かった。

認知症患者の多くはうつ症状を示すが、適切な薬物療法を示した質の高いエビデンスはない。



現状では、主要学会は抗うつ薬の認知症患者への適用を支持しており、セルトラリンなどが第1選択として処方されている。高齢化が進む先進国では、認知症患者のうつは臨床的に重要な領域であると考えた英National Institute of Health Research (NIHR)は、著者らに臨床試験の実施を依頼した。



そこで著者らは、英国で最もよく処方されているセルトラリンとミルタザピンの有効性と安全性を偽薬と比較する、二重盲検の無作為化試験HTA-SADDを実施した。

イングランドの高齢者精神医療施設9カ所で、07年1月から09年12月まで、患者登録を実施。NINCDS-ADRDA基準に基づいてアルツハイマー病疑いまたは可能性例と判定された患者の中から、4週間以上うつ状態が続いており、Cornell認知症抑うつ尺度（CSDD）のスコアが8以上の人々を選んだ。臨床的に危険な状態（自殺リスクが高いなど）の患者などは除外した。

登録患者は、1対1対1の割合で、セルトラリン（目標用量は150mg、107人、平均年齢80歳）、ミルタザピン（同45mg、108人、79歳）、偽薬（111人、79歳）のいずれかに無作為に割り付けた。4週と8週の時点でCSDDスコアを調べ、いずれも4以上なら増量するとした。

主要アウトカム評価指標は、13週時点のCSDDスコアに基づくうつ状態の軽減とし、2次評価指標として39週時点のCSDDスコアなどを評価した。

39週までの脱落は、セルトラリン群が35％、ミルタザピン群が29％、偽薬群が24％だった。1日用量の平均は、登録患者全体ではセルトラリンが70mg、ミルタザピンが24mgで、脱落患者を除くとそれぞれ95mgと30mgになった。



どのグループでも、うつ症状はベースラインに比べ軽快化していた。13週時点でCSDDスコアの低下が最も大きかったのは偽薬群で、-5.6ポイント。セルトラリン群では-3.9ポイント、ミルタザピン群では-5.0ポイントだった。39週時点では、それぞれ-4.8ポイント、-4.0ポイント、-5.0ポイントだった。



線形回帰混合モデルを利用し、ベースラインのCSDDスコア、時間、施設で調整して平均差を求めた。ベースラインから13週までのうつスコアの低下レベルに有意差はなかった。セルトラリン群の偽薬群との平均差は1.17（95％信頼区間-0.23から2.58、P＝0.10）、ミルタザピン群の偽薬群との平均差は0.01（-1.37から1.38、P＝0.99）で、セルトラリン群をミルタザピン群と比較した場合の平均差は1.16（-0.25から2.57、P＝0.11）だった。39週の時点でも結果は同様で、偽薬群との平均差は、セルトラリン群が0.37（-1.12から1.87、P＝0.62）、ミルタザピン群は-0.66（-2.12から0.79、P＝0.37）だった。



ベースラインのうつ病の程度で患者を層別化（CSDDのスコアが8～11か12以上か）して分析したが、やはりこれら2種類の抗うつ薬の有効性は認められなかった。

39週までの消化器症状、神経学的症状などの有害事象発生率を調べたところ、偽薬群は29人（26％）、セルトラリン群は46人(43％、P＝0.010)、ミルタザピン群は44人(41％、P＝0.031)だった。

この試験では、偽薬を上回る抗うつ薬の利益は見られず、有害事象のリスクは有意に高かった。著者らは、「得られた結果はネガティブだが臨床的には重要だ」という。この試験では、割り付けから13週時点で偽薬群のうつスコアにも改善が見られたことから、「うつ症状が見られてから3カ月程度は観察を継続し、変化が見られないケースにのみ抗うつ薬の使用を考慮した方が良いのではないか」と著者らは述べている。いずれにせよ、認知症患者のうつに対する第1選択としてこれらの薬剤を用いることについては、再考が必要だろう。



【開催日】

2011年8月10日

【文献名】

Julia Hippisley-Cox : Unintended effects of statins in men and women in England and Wales: population based cohort study using the QResearch database(¶1)  BMJ 2010;340:c2197



【要約】

＜Objective＞

To quantify the unintended effects of statins according to type, dose, and duration of use.



＜Design＞

Prospective open cohort study using routinely collected data. 



＜Setting＞
368 general practices in England and Wales supplying data to the QResearch database. 【Participants】 2 004 692 patients aged 30-84 years of whom 225 922 (10.7%) were new users of statins: 159 790 (70.7%) were prescribed simvastatin(訳注；リポバスR), 50 328 (22.3%) atorvastatin(訳注；リピトールR), 8103 (3.6%) pravastatin(訳注；メバロチンR), 4497 (1.9%) rosuvastatin(訳注；クレストールR), and 3204 (1.4%) fluvastatin(訳注；ローコール).



＜Methods＞

Cox proportional hazards models were used to estimate effects of statin type, dose, and duration of use. The number needed to treat (NNT) or number needed to harm (NNH) were calculated and numbers of additional or fewer cases estimated for 10 000 treated patients.



＜Main outcome measure＞

First recorded occurrence of cardiovascular disease, moderate or serious myopathic events, moderate or serious liver dysfunction, acute renal failure, venous thromboembolism, Parkinson’s disease,dementia, rheumatoid arthritis, cataract, osteoporotic fracture, gastric cancer, oesophageal cancer, colon cancer, lung cancer, melanoma, renal cancer, breast cancer, or prostate cancer.



＜Results＞

(To help reading, I added the number to the original article.　See Table6 in original article.)

1.Individual statins were not significantly associated with risk of Parkinson’s disease, rheumatoid arthritis, venous thromboembolism, dementia, osteoporotic fracture, gastric cancer, colon cancer, lung cancer, melanoma, renal cancer, breast cancer, or prostate cancer. 

2.Statin use was associated with decreased risks of oesophageal cancer but increased risks of moderate or serious liver dysfunction, acute renal failure, moderate or serious myopathy, and cataract. 

3. Adverse effects were similar across statin types for each outcome except liver dysfunction where risks were highest for fluvastatin. A dose-response effect was apparent for acute renal failure and liver dysfunction. All increased risks persisted during treatment and were highest in the first year. After stopping treatment the risk of cataract returned to normal within a year in men and women. Risk of oesophageal cancer returned to normal within a year in women and within 1-3 years in men. Risk of acute renal failure returned to normal within 1-3 years in men and women, and liver dysfunction within 1-3 years in women and from three years in men.

4. Based on the 20% threshold for cardiovascular risk, for women the NNT with any statin to prevent one case of cardiovascular disease over five years was 37 (95% confidence interval 27 to 64) and for oesophageal cancer was 1266 (850 to 3460) and for men the respective values were 33 (24 to 57) and 1082 (711 to 2807).

5. In women the NNH for an additional case of acute renal failure over five years was 434 (284 to 783), of moderate or severe myopathy was 259 (186 to 375), of moderate or severe liver dysfunction was 136 (109 to 175), and of cataract was 33 (28 to 38). Overall, the NNHs and NNTs for men were similar to those for women, except for myopathy where the NNH was 91 (74 to 112).



＜Conclusions＞

Claims of unintended benefits of statins, except for oesophageal cancer, remain unsubstantiated, although potential adverse effects at population level were confirmed and quantified. Further studies are needed to develop utilities to individualise the risks so that patients at highest risk of adverse events can be monitored closely.

【開催日】

2011年8月3日

【文献名】

Shimoli V. Shah and Brian F. Gage. Cost-Effectiveness of Dabigatran for Stroke Prophylaxis in Atrial Fibrillation. (Circulation. 2011;123:2562-2570.)



【要約】

＜Background＞

Recent studies have investigated alternatives to warfarin for stroke prophylaxis in patients with atrial fibrillation (AF), but whether these alternatives are cost-effective is unknown.



＜Methods and Results＞

On the basis of the results from Randomized Evaluation of Long Term Anticoagulation Therapy
(RE-LY) and other trials, we developed a decision-analysis model to compare the cost and quality-adjusted survival of various antithrombotic therapies. We ran our Markov model in a hypothetical cohort of 70-year-old patients with AF using a cost-effectiveness threshold of $50 000/quality-adjusted life-year. We estimated the cost of dabigatran as US $9 a day. For a patient with an average risk of major hemorrhage (3%/y), the most cost-effective therapy depended on stroke risk. For patients with the lowest stroke rate (CHADS 2 stroke score of 0), only aspirin was cost-effective. For patients with a moderate stroke rate (CHADS 2 score of 1 or 2), warfarin was cost-effective unless the risk of hemorrhage was high or quality of international normalized ratio control was poor (time in the therapeutic range 57.1%). For patients with a high stroke risk (CHADS 2 stroke score 3), dabigatran 150 mg (twice daily) was cost-effective unless international normalized ratio control was excellent (time in the therapeutic range  72.6%). Neither dabigatran 110 mg nor dual therapy (aspirin and clopidogrel) was cost-effective.



＜Conclusions＞

Dabigatran 150 mg (twice daily) was cost-effective in AF populations at high risk of hemorrhage or high risk of stroke unless international normalized ratio control with warfarin was excellent. Warfarin was cost-effective in moderate-risk AF populations unless international normalized ratio control was poor.



【開催日】

2011年7月26日

【タイトル】

風邪に対するプラセボの効果～ランダム化比較試験～



【文献名】

Barret B. Brown R. et al. Placebo Effects and the Common Cold: A Randomized Controlled Trial. Ann Fam Med. 2011; 312-322.



【要約】

＜PURPOSE＞

 We wanted to determine whether the severity and duration of illness caused by the common cold are influenced by randomized assignment to open- label pills, compared with conventional double-blind allocation to active and placebo pills, compared with no pills at all.



＜METHODS＞

We undertook a randomized controlled trial among a population with new-onset common cold. Study participants were allocated to 4 parallel groups: (1) those receiving no pills, (2) those blinded to placebo, (3) those blinded to echina- cea, and (4) those given open-label echinacea. Primary outcomes were illness dura- tion and area-under-the-curve global severity. Secondary outcomes included neu- trophil count and interleukin 8 levels from nasal wash at intake and 2 days later.



＜RESULTS＞

Of 719 randomized study participants, 2 were lost and 4 exited early. Participants were 64% female, 88% white, and aged 12 to 80 years. Mean ill- ness duration for each group was 7.03 days for those in the no-pill group, 6.87 days for those blinded to placebo, 6.34 days for those blinded to echinacea, and 6.76 days for those in the open-label echinacea group. Mean global sever- ity scores for the 4 groups were no pills, 286; blinded to placebo, 264; blinded to echinacea, 236; and open-label echinacea, 258. Between-group differences were not statistically significant. Comparing the no-pill with blinded to placebo groups, differences (95% confidence interval [CI]) were ?0.16 days (95% CI, ?0.90 to 0.58 days) for illness duration and ?22 severity points (95% CI, ?70 to 26 points) for global severity. Comparing the group blinded to echinacea with the open-label echinacea group, differences were 0.42 days (95% CI, ?0.28 to 1.12 days) and 22 severity points (95% CI, ?19 to 63 points). Median change in interleukin 8 concentration and neutrophil cell count, respectively by group, were 30 pg/mL and 1 cell for the no-pill group, 39 pg/mL and 1 cell for the group binded to placebo, 58 pg/mL and 2 cells for the group blinded to echinacea, and 70 pg/mL and 1 cell for the group with open-label echinacea, also not statisti- cally significant. Among the 120 participants who at intake rated echinacea’s effectiveness as greater than 50 on a 100-point scale for which 100 is extremely effective, illness duration was 2.58 days shorter (95% CI, ?4.47 to ?0.68 days) in those blinded to placebo rather than no pill, and mean global severity score was 26% lower but not significantly different (?97.0, 95% CI, ?249.8 to 55.8 points). In this subgroup, neither duration nor severity differed significantly between the group blinded to echinacea and the open-label echinacea group.



＜CONCLUSIONS＞

Participants randomized to the no-pill group tended to have longer and more severe illnesses than those who received pills. For the subgroup who believed in echinacea and received pills, illnesses were substantively shorter and less severe, regardless of whether the pills contained echinacea. These findings sup- port the general idea that beliefs and feelings about treatments may be important and perhaps should be taken into consideration when making medical decisions.



【開催日】

2011年7月20日

【文献名】

Stuart J. Connolly, M.D. Dabigatran versus Warfarin in Patients with Atrial Fibrillation. N Engl J Med 2009; 361:1139-1151



【要約】

＜Background＞

Warfarin reduces the risk of stroke in patients with atrial fibrillation but increases the risk of hemorrhage and is difficult to use. Dabigatran is a new oral direct thrombin inhibitor.



＜Methods＞

In this noninferiority trial, we randomly assigned 18,113 patients who had atrial fibrillation and a risk of stroke to receive, in a blinded fashion, fixed doses of dabigatran ? 110 mg or 150 mg twice daily ? or, in an unblinded fashion, adjusted-dose warfarin. The median duration of the follow-up period was 2.0 years. The primary study outcome was stroke or systemic embolism.
  Systemic embolism was defined as an acute vascular occlusion of an extremity or organ,documented by means of imaging,surgery,or autopsy.
The primary safety outcome was major hemorrhage.



＜Results＞

Characteristics of the study patients was described table 1 in the original article. The three treatment groups were well balanced with respect to baseline characteristics
Rates of the primary outcome were 1.69% per year in the warfarin group, as compared with 1.53% per year in the group that received 110 mg of dabigatran (relative risk with dabigatran, 0.91; 95% CI, 0.74 to 1.11; P<0.001 for noninferiority) and 1.11% per year in the group that received 150 mg of dabigatran (relative risk, 0.66; 95% CI, 0.53 to 0.82; P<0.001 for superiority). 
The rate of major bleeding was 3.36% per year in the warfarin group, as compared with 2.71% per year in the group receiving 110 mg of dabigatran (P=0.003) and 3.11% per year in the group receiving 150 mg of dabigatran (P=0.31). The rate of hemorrhagic stroke was 0.38% per year in the warfarin group, as compared with 0.12% per year with 110 mg of dabigatran (P<0.001) and 0.10% per year with 150 mg of dabigatran (P<0.001). The mortality rate was 4.13% per year in the warfarin group, as compared with 3.75% per year with 110 mg of dabigatran (P=0.13) and 3.64% per year with 150 mg of dabigatran (P=0.051).

The only adverse effect that was significantly more common with dabigatran than with warfarin was dyspepsia（Table.4）Dyspepsia occurred in 348 patients (5.8%) in the warfarin group and in 707 patients (11.8%) and 688 patients (11.3%) in the 110-mg and 150-mg dabigatran groups, respectively (P<0.001 for both comparisons)



 
 ＜Conclusions＞

In patients with atrial fibrillation, dabigatran given at a dose of 110 mg was associated with rates of stroke and systemic embolism that were similar to those associated with warfarin, as well as lower rates of major hemorrhage. Dabigatran administered at a dose of 150 mg, as compared with warfarin, was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage.



【開催日】

2011年6月22日

【文献名】

Chun-Sick Eom, Sang Min Park, Seung-Kwon Myung, Jae Moon Yun, and Jeong-Soo Ahn. Use of Acid-Suppressive Drugs and Risk of Fracture: A Meta-analysis of Observational Studies. Ann Fam Med . 2011 9: 257-267.



【要約】

＜背景＞

PPIは破骨細胞の酸生成も抑制するため骨折に予防的に働くと考えられてきたが、むしろ骨折が増えるという知見が出てきている。PPIと骨折リスクの増加についての研究は議論の一致をみておらず、これまでメタアナリシスが存在しないことからメタアナリシスを実施することとした。



＜文献検索＞

MEDLINE、EMBASE、Cochrane Libraryを使用。



＜研究選別＞

RCT、コホート内症例対照研究、症例対照研究を利用。骨折リスクのリストを作成。二人の研究者が独立して評価される研究の妥当性を評価。



＜主解析＞

PPI、H2ブロッカー、あるいはその両者の使用と骨折リスクとの関係



＜結果＞

1809の文献がヒットしたが選別の結果、最終解析に残ったのは5つの症例対照研究、3つのコホート内症例対照研究、3つのコホートであった。RCTは最終選別までに除外され残らなかった。

　

●主解析結果

PPIで骨折リスク上昇を認めた（adjusted OR 1.29: 95%CI 1.18-1.41, I2 69.8%, n=10）
H2ブロッカーで骨折リスク上昇認めず（adjusted OR 1.10: 95%CI 0.99-1.23, I2 86.3%, n=7）

●サブグループ解析結果
Table.2参照。



●出版バイアスの評価
特に影響はないと考えられた（funnel plot、Egger test）。



＜Discussion＞

PPIと骨折リスク増加が認められた。H2ブロッカーと骨折リスクには明らかな関係は見いだせなかったが、サブグループ解析ではhigh-quality methodology studyと5つ以上の変数について補正した解析では骨折との関連性が示唆されており今後のさらなる4研究が必要。
　限界として①観察研究が含まれるのでバイアスが含まれる可能性がるが、これについては様々なサブグループ解析を行うことで補った。②Egger testは出版バイアス評価としては信頼性が劣る。③栄養データについては評価していない。④胃の疾患の有無の評価をしていない。



＜まとめ＞

PPIは骨折リスクを中等度上昇させる可能性がある。H2ブロッカーに関してはその可能性は示唆されなかった。ORは2以下で僅かな影響と考えられるもののcommon diseaseでもあり社会への影響は大きい。臨床家は特に65歳以上の女性に対してこれらの処方するときには慎重に考慮をするべきである。用量についても望ましい結果得られるために必要な最低限の量にとどめることが勧められる。



【考察とディスカッション】

弱いながらもPPIと骨折リスク上昇の可能性が示唆されている。やはり制酸薬を使用する際は必要最小限のものとすることを目標とするのがよさそうである。
以下、全体でのディスカッション
NSAIDSの投与にあわせてPPIを使用している患者も多い。この文献の結果を受けて、自分自身の投薬行動を見直す機会としたい。



【開催日】

2011年6月22日

【文献名】

辻野元祥，これで決まり！おすすめ処方　糖尿病編，日本医事新報，2011年4月9日；No.4537：42-46



【要約】


　糖尿病患者をⅠ～Ⅳの４つのグループに分けて初めて薬物治療を開始する場合および、そこからステップアップする場合の代表的な処方例をあげる。


Ⅰ．痩せ型かつ軽中等症
　このグループに入る患者は、中等度のインスリン分泌不全、特にインスリン初期分泌障害に伴い空腹時血糖以上に食後高血糖が目立つという特徴を持つ方が多い。したがって、まずは、食後高血糖を是正する目的で最初の薬剤が選択される。
＜処方例＞（2～3ヶ月毎に見直し）



Ⅱ．痩せ型かつ重症
　グループⅠよりもインスリン分泌不全がより進んだ病態。まず、HbA1cが10％以上あるいは尿ケトン体強陽性の患者はインスリンを導入すべき。HbA1cが8～10％でも可能な限りインスリン導入が勧められる。しかし、最初からインスリン導入の話をすると逃げ出してしまう患者も少なくない。インスリン導入が困難な場合の処方例を示す。
＜処方例＞（1～2ヶ月毎に見直し）



Ⅲ．中肉～肥満型かつ軽中等症
　若干あるいは高度のインスリン抵抗性があり、グループⅠ同様にインスリン初期分泌障害があるとしても高度ではない病態。ターゲットはインスリン抵抗性、次いでインスリン初期分泌障害となる。
＜処方例＞（2～3ヶ月毎に見直し）



Ⅳ．中肉～肥満型かつ重症
　HbA1cが10％以上あるいは尿ケトン体陽性の患者は痩せ型でなくてもインスリンを導入すべき。HbA1cが8～10％の患者では、尿ケトン体陰性であることを確認してメトホルミンを、食事療法が可能であれば、早期からピオグリタゾンを併用するか、DPP4阻害薬を併用する。
＜処方例＞（1～2ヶ月毎に見直し）



【考察とディスカッション】
糖尿病患者を4つのグループに分け、グループ毎にStepを踏んで治療を組み立てていくという考え方はこれまでも何気なくやってきたことではあったが、今回の記事を読んで、頭の中を整理する事ができた。しかも、DPP4阻害薬などインクレチン製剤も組み合わせた形で整理する事ができた。しかし、DPP4阻害薬とSU薬の併用で重篤な低血糖が起きるなど危険性も把握したうえで治療を組み立てる必要がある。
以下全体でのディスカッション。
　現時点ではDPP4阻害薬に関するエビデンスは乏しく、また多くの症例が長期で服薬した場合の副作用なども明らかにはなっていない。今回の文献はエキスパートオピニオンとして参考にすべきものであろう。
　ビグアナイド製材やSU剤が経口血糖降下薬の主役であることは当面変わらないだろう。その他の今後のエビデンスの出現に期待したい。
　ビグアナイド製剤であるメトホルミンはこれまで1日750mgまでの使用が限度であったが、2250mgまで使用可能な製剤が発売され1年が経過、長期処方が可能になったところである。こちらも注目すべき情報である。




【開催日】

2011年6月15日

【文献名】
Erika Ringdahl, Sandesh Pndit. Treatment of Knee Osteoarthritis. Am Fam Physician. 2011;83(11):1287-1292.

【要約】

＜Background＞
Osteoarthritis is a degenerative joint disease occurring primarily in older adults. It is characterized by erosion of the articular cartilage, hypertrophy of bone at the margins (i.e., osteophytes), and subchondral sclerosis.1  Arthritis is the leading cause of disability in the United States,2 and osteoarthritis is the most common condition affecting synovial joints.3 
Despite its widespread prevalence, however, the precise etiology, pathogenesis, and progression of osteoarthritis are unknown. Several factors may make a person vulnerable to the disease (Table 1).


＜Diagnosis of Osteoarthritis＞
The differential diagnosis of chronic knee pain is given in original paper (table2).
The criteria for diagnosing knee osteoarthritis are based on the presence of knee pain plus at least three of the six clinical characteristics listed in Table 3.5,6 The addition of laboratory and radiographic criteria enchances the diag- nostic accuracy; however, these tests are not necessary for all patients. In most patients, the history, physical examination, and radiography are all that is needed.


＜Treatment of Osteoarhritis＞

The evidence ratings of treatment of knee osteoarthritis are below.
# The use of braces and heel wedges may also be effective. There is some evidence that the use of a lateral heel wedge decreases the use of nonsteroidal anti-inflammatory drugs (NSAIDs). Similar evidence suggests that a brace and lateral wedge insole may have a small beneficial effect.
# Ginger may provide some clinical benefit in patients with knee osteoarthritis; patients who took 255mg of ginger extract twice daily had a reduction in pain (63% compared with 50% in the placebo group).
# Topical NSAIDs were superior to placebo in relieving pain, but only for the first two weeks of treatment. Topical NSAIDs were less effective than oral NSAIDs.
#  Arthroscopic surgery is not an appropriate treatment unless there is evidence of loose bodies or mechanical symptoms such as locking, giving way, or catching. 
#  The main indication for total knee arhtroplasty is relief of pain associated with knee osteoarthritis if nonsurgical treatment has been ineffective. The complication rate of total knee replacement is 5.4% of patients.



【開催日】

2011年6月15日