今日の臨床サポート 今日の臨床サポート

著者: 眞島任史 日本医科大学付属病院 整形外科

監修: 酒井昭典 産業医科大学 整形外科学教室

著者校正/監修レビュー済:2023/08/02
患者向け説明資料

改訂のポイント:
  1. 『変形性膝関節症診療ガイドライン2023』の発刊に伴い改訂を行なった。
  1. 「概要・推奨」に新ガイドラインのBackground question、Clinical questionについて紹介している。
  1. 新ガイドラインの特徴は以下の通りである。
  1. 今回のガイドラインは海外のガイドラインを日本の現状と比較し適合化させた前回のものと異なり、あらたにクリニカルクエスチョンを作成している。
  1. クリニカルクエスチョン作成に当たっては、学会員だけでなく一般市民から「変形性膝関節症について何が知りたいか」の質問・要望事項を受けて作成した。海外のガイドラインは多くが内科系の医療者によって作成されたものであるが、本ガイドラインは手術を含めた実際の治療にあたる整形外科医が作成したという点で意義がある。
  1. 参考資料としてサプリメントや多血小板血漿(PRP)療法に関して記載されている。

概要・推奨   

  1. 『変形性膝関節症診療ガイドライン2023』では変形性膝関節症に関する国内外の文献を渉猟しランダム化比較試験のような質の高い研究データを、出版バイアスのようなデータの偏りを限りなく除き分析を行った。病態、自然経過、リスク因子、発症機序や診断に関する10のBackground questionと15のClinical questionからなる。推奨度1と推奨度2のClinical questionの要約を以下に記載する。
  1. 推奨度1:
  1. 変形性膝関節症に対して教育と生活習慣についての指導プログラムは有効である(エビデンスの強さB)
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病態・疫学・診察 

疫学情報・病態・注意事項  
  1. 日本における膝関節痛の有訴率は15%程度である[1]
  1. 55歳以上の人口の25%は膝痛を持っているという海外の調査もある[2]
  1. 疼痛を有する症候性変形性膝関節症は1000万人に上ると推定されている[3]
  1. 50歳以上の内側半月板の症状を呈する患者の3.4%が特発性膝関節骨壊死であったとの報告がある[4]
  1. 化膿性関節炎や結核性関節炎の頻度は少ないが、診断が遅れると治療に難渋するので必ず否定しなければならない。
  1. 関連痛や動脈病変は見落とされることが多いので、注意を要する。
 
関連画像:
  1. 中高年の膝痛の原因は、主なものに変形性膝関節症、関節リウマチ、化膿性関節炎、結晶沈着性関節炎(痛風、偽通風)、膝関節骨壊死(特発性膝関節顆部骨壊死[5])、結核性関節炎、半月板損傷、関節遊離体、神経病性関節症、脆弱性骨折 、腱・靭帯付着部炎、骨腫瘍、転移性骨腫瘍、閉塞性動脈硬化症、股関節・腰椎疾患による関連痛などがある。
  1. 変形性膝関節症のX線分類例としてKellgren-Lawrence分類がある[6]
 
変形性膝関節症のX線分類(Kellgren-Lawrence分類)

Gradeが進んでいる症例で、ADLの障害が強ければ手術治療を考慮する。
a:Grade 0
b:Grade 1
c:Grade 2
d:Grade 3
e:Grade 4

出典

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変形性膝関節症のX線分類(Kellgren-Lawrence分類)

Gradeが進んでいる症例で、ADLの障害が強ければ手術治療を考慮する。

出典

著者提供
 
関節リウマチの膝の典型的X線写真

変形性関節症は骨増殖性変化が主体で、内側もしくは外側どちらか一方の関節裂隙の狭小化である。関節リウマチは骨萎縮が主体であり、内側・外側両方の関節裂隙が狭小化する。

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偽痛風のX線写真

半月板の石灰化を伴うことがある

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内側半月板後節の断裂

MRI画像(a)と関節鏡視下縫合術の内視鏡写真(b)。MRI画像の矢印は断裂部位を示す。

出典

著者提供
 
  1. 神経病性関節症:<図表>
  1. 脛骨近位の脆弱性骨折:<図表>
  1. 骨巨細胞腫:<図表>
  1. 骨巨細胞腫(Giant Cell Tumor)のCT画像:<図表>
 
  1. 特発性膝関節骨壊死
  1. 病歴:75歳女性
    誘因なく2週間前から右膝痛出現。強い夜間痛を訴える。
  1. 診察:膝屈曲位で大腿骨内側顆に圧痛を認めた。
  1. 診断のためのテストとその結果:単純X線写真では内側関節裂隙の狭小化を認め軽度の変形性膝関節症である。
  1. 治療:NSAIDsを投与し、MRIの予約を行った。
  1. 転帰:MRIでは大腿骨内側顆の骨壊死であった。足底挿板を装用させ、NSAIDsで保存加療した。
  1. 追記:若く活動性が高ければ高位脛骨骨切り術の適応になる。変形性関節症が強い場合には人工膝関節置換術の適応になる。
 
特発性膝関節骨壊死

a:膝関節単純X線写真正面像。骨壊死ははっきりしない。
b:膝関節単純X線写真側面像
c:上図a, bのMRI前額断。壊死の範囲が明らかである。
d:上図a, bのMRI矢状断。壊死の範囲が明らかである。

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問診・診察のポイント  
問診:
  1. 以下の確認を行う。

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最新のエビデンスに基づいた二次文献データベース「今日の臨床サポート」。
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文献 

H Sakakibara, S K Zhu, M Furuta, T Kondo, M Miyao, S Yamada, T Hideaki
Knee pain and its associations with age, sex, obesity, occupation and living conditions in rural inhabitants of Japan.
Environ Health Prev Med. 1996 Oct;1(3):114-8. doi: 10.1007/BF02931201.
Abstract/Text Factors associated with knee pain were investigated using 871 self-administered questionnaires (405 men and 466 women) from residents aged over 30 years in a rural area of Japan. The prevalence of knee pain increased with age, particularly in women over 50. It was significantly higher in women than in men. Body mass index (BMI) was significantly related to knee pain in women, though not in men. With reference to occupational factors, frequent heavy lifting on the job was significantly associated with knee pain in both men and women, whereas job-related standing and walking showed no such relationship. As for living conditions, residence on rather steep mountain slopes and the habit of sitting on Japanese tatami mats were significant factors related to knee pain in men, but not in women. There was no association of knee pain with the style of toilet (Japanese or Western). After controlling for all significant factors by multiple logistic regression analysis, age, heavy lifting, and residence on steep slopes were found to be independent factors related to knee pain in men; and age, BMI, and heavy lifting were the factors in women.

PMID 21432433
T E McAlindon, C Cooper, J R Kirwan, P A Dieppe
Knee pain and disability in the community.
Br J Rheumatol. 1992 Mar;31(3):189-92.
Abstract/Text In order to investigate the strength of any relationship between knee pain and disability, a postal questionnaire was sent to 2102 men and women aged over 55 registered at a general practice in Bristol. A response rate of 80.6% was achieved at second reminder. Knee pain was common particularly in women (27.6% overall). Disability was also more frequently reported in women (P less than 0.05) and rose with increasing age. Respondents with knee pain had significantly more disability relating to upper as well as lower limb activities (P less than 0.05).

PMID 1540789
Shigeyuki Muraki, Toru Akune, Hiroyuki Oka, Yuyu Ishimoto, Keiji Nagata, Munehito Yoshida, Fumiaki Tokimura, Kozo Nakamura, Hiroshi Kawaguchi, Noriko Yoshimura
Incidence and risk factors for radiographic knee osteoarthritis and knee pain in Japanese men and women: a longitudinal population-based cohort study.
Arthritis Rheum. 2012 May;64(5):1447-56. doi: 10.1002/art.33508.
Abstract/Text OBJECTIVE: To examine the incidence and progression of radiographic knee osteoarthritis (OA) and the incidence of knee pain, and their risk factors in Japan, using the large-scale population of the nationwide cohort study ROAD (Research on Osteoarthritis/osteoporosis Against Disability).
METHODS: Subjects from the ROAD study who had been recruited in 2005-2007 were followed up with knee radiography 3 years later. A total of 2,262 paired radiographs (74.4% of the original sample) were scored using the Kellgren/Lawrence (K/L) grading system, and the incidence and progression rate of knee OA was examined. The incidence rate of knee pain was also examined. In addition, risk factors were tested for their association with incident and progressive radiographic knee OA and incident knee pain.
RESULTS: Given the ∼3.3-year followup, the rate of incident K/L grade ≥2 radiographic knee OA was 6.9% and 11.9% in men and women, respectively, while that of K/L grade ≥3 knee OA was 8.4% and 13.9% in men and women, respectively. The rate of progressive knee OA was 17.8% and 22.3% in men and women, respectively. The incident rate of knee pain was 21.2% and 27.3% in men and women, respectively. Female sex was a risk factor for incident K/L grade ≥2 knee OA, but was not associated with incident K/L grade ≥3 knee OA or progressive knee OA. Knee pain was a risk factor for incident and progressive knee OA. Previous knee injury was a risk factor for knee pain but not for radiographic knee OA.
CONCLUSION: The present longitudinal study revealed a high incidence of radiographic knee OA in Japan.

Copyright © 2012 by the American College of Rheumatology.
PMID 22135156
Dietrich Pape, Romain Seil, Ekkehard Fritsch, Stefan Rupp, Dieter Kohn
Prevalence of spontaneous osteonecrosis of the medial femoral condyle in elderly patients.
Knee Surg Sports Traumatol Arthrosc. 2002 Jul;10(4):233-40. doi: 10.1007/s00167-002-0285-z. Epub 2002 Apr 9.
Abstract/Text Aseptic osteonecrosis of the medial femoral condyle has recently been reported as a complication of arthroscopic surgery. The time interval between the onset of symptoms and pathognomonic MRI changes (diagnostic window) is not known for osteonecrosis of the knee. To determine the prevalence of early-stage spontaneous osteonecrosis of the knee (SONK) we prospectively examined 176 patients by MRI between May 1998 and December 1999. In six patients MRI revealed a bone marrow edema pattern and subtle subchondral bone changes in the medial condyle consistent with early-stage SONK (prevalence of 3.4%); in the 53 patients older than 65 years the prevalence was 9.4%. In 10 patients (5.7%) the bone and marrow changes on MRI imaging either resolved on follow-up MRI and were regarded as transient epiphyseal lesions or were considered to be reactive changes due to underlying degenerative articular disease. Including MRI in the preoperative diagnostic procedures could avoid missing the diagnosis of avascular necrosis before planning an operative treatment of suspected meniscal tears in elderly patients.

PMID 12172718
S Ahlbäck, G C Bauer, W H Bohne
Spontaneous osteonecrosis of the knee.
Arthritis Rheum. 1968 Dec;11(6):705-33.
Abstract/Text
PMID 5700639
J H KELLGREN, J S LAWRENCE
Radiological assessment of osteo-arthrosis.
Ann Rheum Dis. 1957 Dec;16(4):494-502.
Abstract/Text
PMID 13498604
Sharon L Kolasinski, Tuhina Neogi, Marc C Hochberg, Carol Oatis, Gordon Guyatt, Joel Block, Leigh Callahan, Cindy Copenhaver, Carole Dodge, David Felson, Kathleen Gellar, William F Harvey, Gillian Hawker, Edward Herzig, C Kent Kwoh, Amanda E Nelson, Jonathan Samuels, Carla Scanzello, Daniel White, Barton Wise, Roy D Altman, Dana DiRenzo, Joann Fontanarosa, Gina Giradi, Mariko Ishimori, Devyani Misra, Amit Aakash Shah, Anna K Shmagel, Louise M Thoma, Marat Turgunbaev, Amy S Turner, James Reston
2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee.
Arthritis Care Res (Hoboken). 2020 Feb;72(2):149-162. doi: 10.1002/acr.24131. Epub 2020 Jan 6.
Abstract/Text OBJECTIVE: To develop an evidence-based guideline for the comprehensive management of osteoarthritis (OA) as a collaboration between the American College of Rheumatology (ACR) and the Arthritis Foundation, updating the 2012 ACR recommendations for the management of hand, hip, and knee OA.
METHODS: We identified clinically relevant population, intervention, comparator, outcomes questions and critical outcomes in OA. A Literature Review Team performed a systematic literature review to summarize evidence supporting the benefits and harms of available educational, behavioral, psychosocial, physical, mind-body, and pharmacologic therapies for OA. Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of the evidence. A Voting Panel, including rheumatologists, an internist, physical and occupational therapists, and patients, achieved consensus on the recommendations.
RESULTS: Based on the available evidence, either strong or conditional recommendations were made for or against the approaches evaluated. Strong recommendations were made for exercise, weight loss in patients with knee and/or hip OA who are overweight or obese, self-efficacy and self-management programs, tai chi, cane use, hand orthoses for first carpometacarpal (CMC) joint OA, tibiofemoral bracing for tibiofemoral knee OA, topical nonsteroidal antiinflammatory drugs (NSAIDs) for knee OA, oral NSAIDs, and intraarticular glucocorticoid injections for knee OA. Conditional recommendations were made for balance exercises, yoga, cognitive behavioral therapy, kinesiotaping for first CMC OA, orthoses for hand joints other than the first CMC joint, patellofemoral bracing for patellofemoral knee OA, acupuncture, thermal modalities, radiofrequency ablation for knee OA, topical NSAIDs, intraarticular steroid injections and chondroitin sulfate for hand OA, topical capsaicin for knee OA, acetaminophen, duloxetine, and tramadol.
CONCLUSION: This guideline provides direction for clinicians and patients making treatment decisions for the management of OA. Clinicians and patients should engage in shared decision-making that accounts for patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.

© 2020, American College of Rheumatology.
PMID 31908149
Rinie Geenen, Cécile L Overman, Robin Christensen, Pernilla Åsenlöf, Susana Capela, Karen L Huisinga, Mai Elin P Husebø, Albère J A Köke, Zoe Paskins, Irene A Pitsillidou, Carine Savel, Judith Austin, Afton L Hassett, Guy Severijns, Michaela Stoffer-Marx, Johan W S Vlaeyen, César Fernández-de-Las-Peñas, Sarah J Ryan, Stefan Bergman
EULAR recommendations for the health professional's approach to pain management in inflammatory arthritis and osteoarthritis.
Ann Rheum Dis. 2018 Jun;77(6):797-807. doi: 10.1136/annrheumdis-2017-212662. Epub 2018 May 3.
Abstract/Text Pain is the predominant symptom for people with inflammatory arthritis (IA) and osteoarthritis (OA) mandating the development of evidence-based recommendations for the health professional's approach to pain management. A multidisciplinary task force including professionals and patient representatives conducted a systematic literature review of systematic reviews to evaluate evidence regarding effects on pain of multiple treatment modalities. Overarching principles and recommendations regarding assessment and pain treatment were specified on the basis of reviewed evidence and expert opinion. From 2914 review studies initially identified, 186 met inclusion criteria. The task force emphasised the importance for the health professional to adopt a patient-centred framework within a biopsychosocial perspective, to have sufficient knowledge of IA and OA pathogenesis, and to be able to differentiate localised and generalised pain. Treatment is guided by scientific evidence and the assessment of patient needs, preferences and priorities; pain characteristics; previous and ongoing pain treatments; inflammation and joint damage; and psychological and other pain-related factors. Pain treatment options typically include education complemented by physical activity and exercise, orthotics, psychological and social interventions, sleep hygiene education, weight management, pharmacological and joint-specific treatment options, or interdisciplinary pain management. Effects on pain were most uniformly positive for physical activity and exercise interventions, and for psychological interventions. Effects on pain for educational interventions, orthotics, weight management and multidisciplinary treatment were shown for particular disease groups. Underpinned by available systematic reviews and meta-analyses, these recommendations enable health professionals to provide knowledgeable pain-management support for people with IA and OA.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
PMID 29724726
Kusum Sharma, Aman Sharma, Shiv Kumar Sharma, Ramesh Kumar Sen, Mandeep Singh Dhillon, Meera Sharma
Does multiplex polymerase chain reaction increase the diagnostic percentage in osteoarticular tuberculosis? A prospective evaluation of 80 cases.
Int Orthop. 2012 Feb;36(2):255-9. doi: 10.1007/s00264-011-1241-7. Epub 2011 Mar 26.
Abstract/Text PURPOSE: Multiplex Polymerase Chain Reaction (MPCR) is a technique in which two or more gene targets are amplified in a single reaction. This has increased sensitivity of diagnosis as a single gene target may be absent in some Mycobacterium tuberculosis strains.
METHODS: MPCR using two target genes specific for Mycobacterium tuberculosis, that is, IS6110 and MPB 64, ZN staining and Mycobacterial culture were performed on synovial fluid/pus samples of 80 (three confirmed, 77 suspected) patients of osteoarticular tuberculosis and 25 non tuberculosis patients.
RESULTS: MPCR had a sensitivity of 100% in confirmed cases and 81.8% in clinically suspected cases. AFB was positive in one patient and Mycobacterial culture was positive in three patients. MPCR also had 100% specificity; MPB64 was positive in five patients in which IS6110 was negative whereas IS6110 was positive in two patients in which MPB64 was negative.
CONCLUSIONS: MPCR is a sensitive and specific method for diagnosis of paucibacilliary conditions such as osteoarticular tuberculosis.

PMID 21442201
Cleveland Clinic: Current Clinical Medicine, 2nd ed. Saunders,2010; 1129-1134.
Firestein: Kelley’s Textbook of Rheumatology, 8th ed.( Chapter 53 Imaging Modalities in Rheumatic Disease),Saunders;2008:805.
David S Jevsevar, Peter B Shores, Kyle Mullen, Danielle M Schulte, Gregory A Brown, Deborah S Cummins
Mixed Treatment Comparisons for Nonsurgical Treatment of Knee Osteoarthritis: A Network Meta-analysis.
J Am Acad Orthop Surg. 2018 May 1;26(9):325-336. doi: 10.5435/JAAOS-D-17-00318.
Abstract/Text INTRODUCTION: Knee osteoarthritis (KOA) is a significant health problem with lifetime risk of development estimated to be 45%. Effective nonsurgical treatments are needed for the management of symptoms.
METHODS: We designed a network meta-analysis to determine clinically relevant effectiveness of nonsteroidal anti-inflammatory drugs, acetaminophen, intra-articular (IA) corticosteroids, IA platelet-rich plasma, and IA hyaluronic acid compared with each other as well as with oral and IA placebos. We used PubMed, EMBASE, and Cochrane Central Register of Controlled Trials to perform a systematic search of KOA treatments with no date limits and last search on October 7, 2015. Article inclusion criteria considered the following: target population, randomized controlled study design, English language, human subjects, treatments and outcomes of interest, ≥30 patients per group, and consistent follow-up. Using the best available evidence, two abstractors independently extracted pain and function data at or near the most common follow-up time.
RESULTS: For pain, all active treatments showed significance over oral placebo, with IA corticosteroids having the largest magnitude of effect and significant difference only over IA placebo. For function, no IA treatments showed significance compared with either placebo, and naproxen was the only treatment showing clinical significance compared with oral placebo. Cumulative probabilities showed naproxen to be the most effective individual treatment, and when combined with IA corticosteroids, it is the most probable to improve pain and function.
DISCUSSION: Naproxen ranked most effective among conservative treatments of KOA and should be considered when treating pain and function because of its relative safety and low cost. The best available evidence was analyzed, but there were instances of inconsistency in the design and duration among articles, potentially affecting uniform data inclusion.

PMID 29688920
D Rhon
Re: Zhang W, Moskowitz RW, Nuki G, et al. OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthritis Cartilage 2008;16:137-62.
Osteoarthritis Cartilage. 2008 Dec;16(12):1585; author reply 1589. doi: 10.1016/j.joca.2008.04.019. Epub 2008 Jun 2.
Abstract/Text
PMID 18515155
越智隆弘、山本一彦、龍順之助編:診断のマニュアルとEBMに基づく治療ガイドライン、財団法人日本リウマチ財団、2004..
American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines
Guidelines for the management of rheumatoid arthritis: 2002 Update.
Arthritis Rheum. 2002 Feb;46(2):328-46.
Abstract/Text
PMID 11840435
F A van Gaalen, S P Linn-Rasker, W J van Venrooij, B A de Jong, F C Breedveld, C L Verweij, R E M Toes, T W J Huizinga
Autoantibodies to cyclic citrullinated peptides predict progression to rheumatoid arthritis in patients with undifferentiated arthritis: a prospective cohort study.
Arthritis Rheum. 2004 Mar;50(3):709-15. doi: 10.1002/art.20044.
Abstract/Text OBJECTIVE: Rheumatoid arthritis (RA) is a common, severe, chronic inflammatory joint disease. Since the disease may initially be indistinguishable from other forms of arthritis, early diagnosis can be difficult. Autoantibodies seen in RA can be detected years before clinical symptoms develop. In an inception cohort of patients with recent-onset arthritis, we undertook this study to assess the predictive value of RA-specific autoantibodies to cyclic citrullinated peptides (CCPs) in patients with undifferentiated arthritis (UA).
METHODS: Anti-CCP2 antibody tests were performed at baseline in 936 consecutive, newly referred patients with recent-onset arthritis. Patients who could not be properly classified 2 weeks after inclusion were categorized as having UA. Patients with UA were followed up for 3 years and evaluated for progression of their disease to RA as defined by the American College of Rheumatology (ACR) 1987 revised criteria.
RESULTS: Three hundred eighteen of 936 patients with recent-onset arthritis were classified as having UA and were available for analysis. After 3 years of followup, 127 of 318 UA patients (40%) had been classified as having RA. RA had developed in 63 of 249 patients (25%) with a negative anti-CCP test and in 64 of 69 patients (93%) with a positive anti-CCP test (odds ratio 37.8 [95% confidence interval 13.8-111.9]). Multivariate analysis of the presence of anti-CCP antibodies and parameters from the ACR criteria identified polyarthritis, symmetric arthritis, erosions on radiographs, and anti-CCP antibodies as significant predictors of RA.
CONCLUSION: Testing for anti-CCP antibodies in UA allows accurate prediction of a substantial number of patients who will fulfill the ACR criteria for RA.

PMID 15022309
S L Wallace, H Robinson, A T Masi, J L Decker, D J McCarty, T F Yü
Preliminary criteria for the classification of the acute arthritis of primary gout.
Arthritis Rheum. 1977 Apr;20(3):895-900.
Abstract/Text The American Rheumatism Association sub-committe on classification criteria for gout analyzed data from more than 700 patients with gout, pseudogout, rheumatoid arthritis, or septic arthritis. Criteria for classifying a patient as having gout were a) the presence of characteristic urate crystals in the joint fluid, and/or b) a topus proved to contain urate crystals by chemical or polarized light microscopic means, and/or c) the presence of six of the twelve clinical, laboratory, and X-ray phenomena listed in Table 5.

PMID 856219
日本痛風・核酸代謝学会 ガイドライン改訂委員会編:高尿酸血症・痛風の治療ガイドライン 第2版、メディカルレビュー社、2010.
Michael A Mont, David R Marker, Michael G Zywiel, John A Carrino
Osteonecrosis of the knee and related conditions.
J Am Acad Orthop Surg. 2011 Aug;19(8):482-94.
Abstract/Text Osteonecrosis (ON) of the knee is a progressive disease that often leads to subchondral collapse and disabling arthritis. Recent studies have identified three distinct pathologic entities, all of which were previously described as knee ON: secondary ON, spontaneous ON of the knee, and postarthroscopic ON. Radiographic and clinical assessment is useful for differentiating these conditions, predicting disease progression, and distinguishing these conditions from other knee pathologies. The etiology, pathology, and pathogenesis of secondary ON of the knee are similar to those found at other sites (eg, hip, shoulder). Spontaneous ON is a disorder of unknown etiology. Postarthroscopic ON has been described as an infrequent but potentially destructive complication. Various treatment modalities (eg, core decompression, bone grafting, high tibial osteotomy, arthroplasty), have been used with varying degrees of success for each type of ON. Secondary ON frequently progresses to end-stage disease, and early surgical intervention is recommended. Initial management of spontaneous ON of the knee and postarthroscopic ON is typically nonsurgical, with observation for clinical or radiographic progression.

PMID 21807916
P R Krey, D A Bailen
Synovial fluid leukocytosis. A study of extremes.
Am J Med. 1979 Sep;67(3):436-42.
Abstract/Text
PMID 474588
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、渡邉裕次、井ノ口岳洋、梅田将光および日本医科大学多摩永山病院 副薬剤部長 林太祐による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、 著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※同効薬・小児・妊娠および授乳中の注意事項等は、海外の情報も掲載しており、日本の医療事情に適応しない場合があります。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適応の査定において保険適応及び保険適応外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適応の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
眞島任史 : 特に申告事項無し[2025年]
監修:酒井昭典 : 講演料(旭化成ファーマ(株),帝人ヘルスケア(株))[2025年]

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