新規アミノ・メチルサイクリン系抗生剤 Omadacycline 市中肺炎トライアル vs モキシフロキサシン

Paratek Announces FDA Approval of NUZYRA™ (Omadacycline)
http://phx.corporate-ir.net/phoenix.zhtml?c=253770&p=irol-newsArticle&ID=2369985


Omadacycline：テトラサイクリン系由来の新しいアミノメチルサイクリン抗生剤
テトラサイクリン耐性の排出・リボソーム防御機構克服された薬剤

肺炎球菌、インフルエンザ桿菌、黄色ブドウ球菌、非定型肺炎(レジオネラ、マイコプラズマ、クラミジア肺炎など）へのin vitro感受性あり
肺炎球菌に感受性あり、肺組織濃度維持する



Omadacycline for Pneumonia Treatment in the Community (OPTIC) trial

臨床効果非劣性証明

Omadacycline for Community-Acquired Bacterial Pneumonia
Roman Stets,., et al.
N Engl J Med 2019; 380:517-527
DOI: 10.1056/NEJMoa1800201

日本の各学会理事会メンバーへの製薬会社からの報酬

各学会のリーダーである理事会のメンバーが製薬メーカーから巨額paymentをもらうと利益相反に関して疑念が持たれてもおかしくない。故に、自らが公開すべきという事だと思う。

Pharmaceutical Company Payments to Executive Board Members of Professional Medical Associations in Japan
Hiroaki Saito, et al.
JAMA Intern Med. Published online February 4, 2019. doi:10.1001/jamainternmed.2018.7283
https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2723072


総額は $6 468 585
講演  $5 279 312；執筆　$412 900 ；コンサルティング $776 373
支払い額中央値  $7486 (中間4分位 [IQR], $1767-$20 277)

支払い額のうち、最大支払い受領理事会メンバー40名に、総額45.8％にあたる$2 960 928 が支払われた
日本内科学会が12名、日本泌尿器科学会が7名、日本皮膚科学会が7名がそのメンバー
最大の支払い対象は日本内科学会の理事で $51 974; IQR, $33 900-$86 349)
日本内科学会理事会メンバーへは総支払い額の20.8％が行ったことになる
同様日本泌尿器科学会 14.9%、日本皮膚科学会 11.1%

19の学会が理事会メンバーへの製薬メーカーへのpaymentに関し公的公開したというエビデンスはつかんでない

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メーカーからの報酬全てが悪というわけでもないだろうが・・・


改変（コピペ＆OCRのため、原文参照を）
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	理事数	報酬受領人数（％）	記録数	value	平均(SD)	中央値(IQR)	最大値
内科学会	22	22 (100)	1176	1343732	61 079 (45 523)	51974(33 900-86 349)	171245
小児科学会	28	25 (89.3)	212	206861	7388 (7053)	3853 (2734-11 552)	23387
老年医療学会	22	16 (72.7)	152	133440	6065 (8952)	1647 (0-11 938)	37639
皮膚科学会	18	18 (100)	671	722150	40 199 (27 825)	34213(20 625-56 909)	97676
外科学会	23	23 (100)	371	385328	16 753 (13 033)	11 887 (7276-23 039)	44536
脳外科学会	23	22 (95.7)	259	242379	10 538 (6800)	10 165 (5893-15150)	27465
産科婦人科学会	32	30 (93.8)	331	317245	9914 (9101)	8099 (2997-13 324)	39356
眼科学会	19	19 (100)	437	514321	27 070 (19 625)	20697(11 470-47 120)	72710
整形外科学会	23	22 (95.7)	432	436479	18 977 (17 255)	17 114 (4853-22 810)	61157
耳鼻咽喉科学会	24	20 (83.3)	248	231281	9637 (12 981)	4870 (1406-11 297)	46463
形成外科・美容外科学会	17	9(52.9)	34	40244	2367 (4959)	497 (0-994)	17427
泌尿器科学会	21	20 (95.2)	846	965081	45 956 (38 683)	34073(19 543-55 358)	122967
麻酔科学会	27	21 (77.8)	133	133353	4939 (6079)	3679(497-6502)	24640
救急医療学会	15	13 (86.7)	76	76380	5092 (4903)	4921 (1293-7251)	17199
病理学会	15	10 (66.7)	64	62083	4139 (4962)	1915 (0-8746)	16283
精神科学会	20	19 (95.0)	344	357815	17 891 (20 805)	8976 (1399-24 721)	69580
放射線科学会	18	17 (94.4)	85	93389	5188 (5475)	4452 (1492-7358)	24293
リハビリテーション学会	23	17 (73.9)	186	181575	7895 (9731)	4572 (1023-7726)	29504
臨床検査学会	17	8(47.1)	70	55265	3251 (6600)	0(0-1084)	21492

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かたやこういう記事
特集◎新専門医制度時代の学会と専門医《2》
製薬マネーの減少が学会を窮地に追い込む
2019/2/7
https://medical.nikkeibp.co.jp/leaf/mem/pub/report/t325/201902/559721.html

京都で開かれた内科学会総会　会費高い割に、内容　かなりしょぼかったと思うが・・・　内科学会理事個人への報酬分　学会本体へ遷せばどう？

The Physical Activity Guidelines for Americans

“2018年11月のAHA年次集会で、連邦政府「身体活動ガイドライン」と VITAL and REDUCE-IT と DECLARE-TIMI 58といった高品質臨床トライアルの報告があった”

VITAL and REDUCE-IT：

Marine n−3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer
JoAnn E. Manson,  et al., for the VITAL Research Group
https://www.nejm.org/doi/full/10.1056/NEJMoa1811403

ランダム化プラシーボ対照2ｘ2区分デザイン、ビタミンDと海産物n-3脂肪酸(1g/日)：男性50歳以上・女性55歳以上一次予防：重大心血管イベント・がん発生率低下認めず 

DECLARE-TIMI 58

アストラゼネカのフォシーガ、DECLARE-TIMI58試験で、幅広い2型糖尿病患者さんにおける心不全による入院または心血管死のリスク低下を示す
https://www.astrazeneca.co.jp/media/press-releases1/2018/2018111401.html
Wiviott S.D et al. ‘Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes’. The New England Journal of Medicine. DOI https://www.nejm.org/doi/full/10.1056/NEJMoa1812389

で、本題の身体活動ガイドライン
The Physical Activity Guidelines for Americans
Katrina L. Piercy, . et al
https://jamanetwork.com/journals/jama/article-abstract/2712935

 (例によってGoogle訳)

PAGは、多数の集団のために様々な健康上の結果を改善するために身体活動の種類と量に関する情報と手引きを提供します。未就学児（3歳から5歳まで）は、成長と発達を促進するために1日を通して身体的に活動的であるべきです。 6歳から17歳までの子供や青年は、毎日60分以上の中程度から激しい運動をするべきです。成人は、少なくとも週に150分から300分の中強度の運動、または週に75分から150分の激しい強度の有酸素運動、または同等の強度と中強度の有酸素運動の組み合わせを行うべきです。彼らはまた、1週間に2日以上筋肉を強化する活動をするべきです。高齢者は、バランストレーニングや有酸素運動、筋力増強などの多成分運動をするべきです。妊娠中および産後の女性は、週に少なくとも150分の中強度の有酸素運動をするべきです。可能な限り慢性疾患や障害を持つ成人は成人のための重要なガイドラインに従うべきであり、そして有酸素運動と筋肉強化活動の両方をするべきです。勧告は、より多くを動かし、より少なく座っていることが、ほぼすべての人に利益をもたらすことを強調しています。身体活動が最も少ない個人は、中程度から活発な身体活動のわずかな増加でさえも最も利益を得ます。身体活動が多いほど、追加の利点があります。有酸素運動と筋力増強の両方の運動が有益です。

Box 1. 身体活動性の健康ベネフィットに関する新しいエビデンス

• 3−5歳小児での骨健康・体重の改善
• 6−13歳では認知機能改善＋追加部位での癌リスク減少
• 脳の健康へのベネフィット、認知機能改善、不安・うつリスク軽減、睡眠・QOL改善
• 高齢者骨折関連外傷リスク減少
• 妊娠女性では、過剰な体重増加、妊娠糖尿病、産後うつのリスク減少
• 慢性医療疾患患者では、総死亡、疾患原因死亡率減少、機能改善、QOL改善

Box 2. Health Benefits Associated With Regular Physical Activity
Children and Adolescents：小児・青年期

• 3−17歳：骨健康の改善、3−17歳：体重改善
• 6−17歳：心臓呼吸・筋肉フィットネス改善、6−13歳：認知改善
• 6−13歳：うつリスク減少

Adults and Older Adults：正常・高齢

• 総死亡率減少
• 心血管死亡率減少
• 心血管（心臓疾患と卒中含め）リスクの減少
• 高血圧リスク減少
• 2型糖尿病リスク減少
• 不都合な脂質特性のリスク減少
• がん（膀胱、乳、子宮内膜、食毒、腎臓、肺、胃）のリスク減少
• 認知改善
• 認知症（アルツハイマー病を含む）リスク減少
• QOL改善
• 不安減少
• うつリスク減少
• 睡眠改善
• 体重増加の緩徐化・減少
• 減量、特にカロリー摂取減少と組み合わせで
• 減量後体重増加予防
• 骨健康改善
• 身体機能の改善
• 転倒リスク減少（高齢者）
• 転倒関連外傷リスク減少（高齢者）

Box 3. Types and Intensity of Physical Activity
Aerobic Activity

• An activity in which the body’s large muscles move for a sustained amount of time, therefore improving cardiorespiratory fitness. Aerobic activity is also called endurance or cardio activity. Examples include brisk walking, running, or bicycling.

Muscle-Strengthening Activity

• An activity that increases skeletal muscle strength, power, endurance, and mass. Examples include weight lifting or resistance training.

Bone-Strengthening Physical Activity

• An activity that produces a force on the bones, which promotes bone growth and strength. Examples include jumping rope or running.

Balance Activity

• An activity designed to improve individuals’ ability to resist forces within or outside of the body that cause falls while a person is stationary or moving. Examples include lunges or walking backward.

Multicomponent Physical Activity

• An activity that includes more than 1 type of physical activity, such as aerobic, muscle strengthening, and balance training. Examples include some dancing or sports.

Absolute Intensity

• Refers to the rate of work being performed and does not consider the physiologic capacity of the individual. This is often expressed in metabolic equivalent of task (MET) units. Moderate-intensity physical activities such as walking briskly or raking the yard have a MET level of 3 to 5.9 METs.

Relative Intensity

• Takes into account or adjusts for a person’s cardiorespiratory fitness. Someone who is more fit will perceive an exercise to be easier and thus rate it as of lower relative intensity than someone who is less fit.

Box 4. Key Guidelines for Preschool-aged Children and for School-aged Children and Adolescents
Preschool-aged Children

• Preschool-aged children (3 through 5 years) should be physically active throughout the day to enhance growth and development.
• Adult caregivers of preschool-aged children should encourage active play that includes a variety of activity types.

School-aged Children and Adolescents

• It is important to provide young people opportunities and encouragement to participate in physical activities that are appropriate for their age, that are enjoyable, and that offer variety.
• Children and adolescents aged 6 through 17 years should do 60 minutes (1 hour) or more of moderate-to-vigorous physical activity daily

• Aerobic: Most of the 60 minutes or more per day should be either moderate- or vigorous-intensity aerobic physical activity and should include vigorous-intensity physical activity on at least 3 days a week.

• Muscle-strengthening: As part of their 60 minutes or more of daily physical activity, children and adolescents should include muscle-strengthening physical activity on at least 3 days a week.

• Bone-strengthening: As part of their 60 minutes or more of daily physical activity, children and adolescents should include bone-strengthening physical activity on at least 3 days a week.

Box 5. Key Guidelines for Adults

• Adults should move more and sit less throughout the day. Some physical activity is better than none. Adults who sit less and do any amount of moderate-to-vigorous physical activity gain some health benefits.
• For substantial health benefits, adults should do at least 150 minutes (2 hours and 30 minutes) to 300 minutes (5 hours) a week of moderate-intensity, or 75 minutes (1 hour and 15 minutes) to
• 150 minutes (2 hours and 30 minutes) a week of vigorous-intensity aerobic physical activity, or an equivalent combination of moderate- and vigorous-intensity aerobic activity. Preferably, aerobic activity should be spread throughout the week.
• Additional health benefits are gained by doing physical activity beyond the equivalent of 300 minutes (5 hours) of moderate-intensity physical activity a week.
• Adults should also do muscle-strengthening activities of moderate or greater intensity that involve all major muscle groups on
• 2 or more days a week, as these activities provide additional health benefits.

Box 6. Key Guidelines for Older Adults

• The key guidelines for adults also apply to older adults. In addition, the following key guidelines are just for older adults:
• As part of their weekly physical activity, older adults should do multicomponent physical activity that includes balance training as well as aerobic and muscle-strengthening activities.
• Older adults should determine their level of effort for physical activity relative to their level of fitness.
• Older adults with chronic conditions should understand whether and how their conditions affect their ability to do regular physical activity safely.
• When older adults cannot do 150 minutes of moderate-intensity aerobic activity a week because of chronic conditions, they should be as physically active as their abilities and conditions allow.

Box 7. Key Guidelines for Women During Pregnancy and the Postpartum Period

• Women should do at least 150 minutes (2 hours and 30 minutes) of moderate-intensity aerobic activity a week during pregnancy and the postpartum period. Preferably, aerobic activity should be spread throughout the week.
• Women who habitually engaged in vigorous-intensity aerobic activity or who were physically active before pregnancy can continue these activities during pregnancy and the postpartum period.
• Women who are pregnant should be under the care of a health care practitioner who can monitor the progress of the pregnancy. Women who are pregnant can consult their health care practitioner about whether or how to adjust their physical activity during pregnancy and after the child is born.

 Box 8. Key Guidelines for Adults With Chronic Health Conditions and Adults With Disabilities

• Adults with chronic conditions or disabilities, who are able, should do at least 150 minutes (2 hours and 30 minutes) to 300 minutes (5 hours) a week of moderate-intensity, or 75 minutes (1 hour and 15 minutes) to 150 minutes (2 hours and 30 minutes) a week of vigorous-intensity aerobic physical activity, or an equivalent combination of moderate- and vigorous-intensity aerobic activity. Preferably, aerobic activity should be spread throughout the week.
• Adults with chronic conditions or disabilities, who are able, should also do muscle-strengthening activities of moderate or greater intensity that involve all major muscle groups on 2 or more days
• a week, as these activities provide additional health benefits.
• When adults with chronic conditions or disabilities are not able to meet the above key guidelines, they should engage in regular physical activity according to their abilities and should avoid inactivity.
• Adults with chronic conditions or symptoms should be under the care of a health care practitioner. People with chronic conditions can consult a health care professional or physical activity specialist about the types and amounts of activity appropriate for their abilities and chronic conditions.

Box 9. Key Guidelines for Safe Physical Activity

• To do physical activity safely and reduce risk of injuries and other adverse events, people should
• Understand the risks, yet be confident that physical activity can be safe for almost everyone.
• Choose types of physical activity appropriate for their current fitness level and health goals, because some activities are safer than others.
• Increase physical activity gradually over time to meet key guidelines or health goals. Inactive people should “start low and go slow” by starting with lower-intensity activities and gradually increasing how often and how long activities are done.
• Protect themselves by using appropriate gear and sports equipment, choosing safe environments, following rules and policies, and making sensible choices about when, where, and how to be active.
• Be under the care of a health care practitioner if they have chronic conditions or symptoms. People with chronic conditions and symptoms can consult a health care professional or physical activity specialist about the types and amounts of activity appropriate for them.

カナグリフロジンと2型糖尿病 日本人への包括的効果

日本人　カナグル：包括的臨床状態への効果

日本人を含むアジア人種の肥満頻度に比例しないメタボリックシンドロームの罹病率の高さ、内臓脂肪との兼ね合いが課題になっているだけに、以下の脂肪組織・アディポネクチン・インスリン感受性へのSGLT2iの効果は日本人T2D治療にとって頼もしい（別にSGLT2iクラス内比較してるわけじゃないから・・・他のSGLT2iでも同じかもしれないけど)



single-arm, single-center, open-label study という制限
体重および体脂肪量低下効果、ならびにそれに伴うインスリン抵抗性の改善効果確認

特に、CANAの投与による血中アディポネクチン濃度上昇ってのが印象深い

Effect of canagliflozin on the overall clinical state including insulin resistance in Japanese patients with Type 2 diabetes mellitus
Yoko Koike et al.
Diabetes Research and Clinical Practice
DOI: https://doi.org/10.1016/j.diabres.2019.01.029

https://www.diabetesresearchclinicalpractice.com/article/S0168-8227(18)31513-4/fulltext

2型糖尿病日本人患者：24週カナグリフロジン 100mg/日24週間投与

HbA1c、空腹時血糖、血中肝機能、血中アディポネクチン値有意低下

体重、内臓脂肪、皮下脂肪面積、脂肪量・除脂肪量、脂肪肝減少

血中アディポネクチン値変化量は有意に体脂肪・内臓脂肪面積変化に相関

グルコースクランプ検査：glucose infusion rate (GIR)　 3.25 ± 1.53 → 4.11 ± 1.30 mg/kg/min (P ＜ 0.05)

空腹時アディポネクチン変化量と内臓脂肪面積相関
 Pearson’s correlation coefficient.

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