健康な高齢者におけるアスピリン投与による心血管イベント及び出血に対する影響
[title]
Effect of Aspirin on Cardiovascular Events and Bleeding in the Healthy Elderly.
[author]
McNeil JJ, et al. N Engl J Med. 2018.
[Abstract]
Background Aspirin is a well-established therapy for the secondary prevention of cardiovascular events. However, its role in the primary prevention of cardiovascular disease is unclear, especially in older persons, who have an increased risk. Methods From 2010 through 2014, we enrolled community-dwelling men and women in Australia and the United States who were 70 years of age or older (or ≥65 years of age among blacks and Hispanics in the United States) and did not have cardiovascular disease, dementia, or disability. Participants were randomly assigned to receive 100 mg of enteric-coated aspirin or placebo. The primary end point was a composite of death, dementia, or persistent physical disability; results for this end point are reported in another article in the Journal. Secondary end points included major hemorrhage and cardiovascular disease (defined as fatal coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal stroke, or hospitalization for heart failure). Results Of the 19,114 persons who were enrolled in the trial, 9525 were assigned to receive aspirin and 9589 to receive placebo. After a median of 4.7 years of follow-up, the rate of cardiovascular disease was 10.7 events per 1000 person-years in the aspirin group and 11.3 events per 1000 person-years in the placebo group (hazard ratio, 0.95; 95% confidence interval [CI], 0.83 to 1.08). The rate of major hemorrhage was 8.6 events per 1000 person-years and 6.2 events per 1000 person-years, respectively (hazard ratio, 1.38; 95% CI, 1.18 to 1.62; P<0.001). Conclusions The use of low-dose aspirin as a primary prevention strategy in older adults resulted in a significantly higher risk of major hemorrhage and did not result in a significantly lower risk of cardiovascular disease than placebo. (Funded by the National Institute on Aging and others; ASPREE ClinicalTrials.gov number, NCT01038583 .).
[memo]
■知らない
enroll :名簿に載せる
community-dwelling :地域社会に暮らす
dementia :痴呆
enteric-coated :腸溶剤の
primary end point :主要評価項目
secondary end point :副次的評価項目
hemorrhage :出血
■使いたい
a well-established therapy for
specially in older persons, who have an increased risk
community-dwelling elderly
After a median of 4.7 years of follow-up,
the rate of cardiovascular disease was 10.7 events per 1000 person-years in the aspirin group
小児における気管支拡張症：診断と治療
[title]
Bronchiectasis in children: diagnosis and treatment.
[author]
Chang AB, et al. Lancet. 2018.
[Abstract]
Bronchiectasis is conventionally defined as irreversible dilatation of the bronchial tree. Bronchiectasis unrelated to cystic fibrosis is an increasingly appreciated cause of chronic respiratory-related morbidity worldwide. Few randomised controlled trials provide high-level evidence for management strategies to treat the children affected by bronchiectasis. However, both decades-old and more recent studies using technological advances support the notion that prompt diagnosis and optimal management of paediatric bronchiectasis is particularly important in early childhood. Although considered to be of a non-reversible nature, mild bronchiectasis determined by radiography might be reversible at any age if treated early, and the lung function decline associated with disease progression could then be halted. Although some management strategies are extrapolated from cystic fibrosis or adult-based studies, or both, non-cystic fibrosis paediatric-specific data to help diagnose and manage these children still need to be generated. We present current knowledge and an updated definition of bronchiectasis, and review controversies relating to the management of children with bronchiectasis, including applying the concept of so-called treatable traits.
[memo]
■知らない
Bronchiectasis :気管支拡張症
dilatation :膨張
cystic fibrosis :嚢胞性繊維症
appreciated :認識された
morbidity :病的状態
prompt :迅速な
optimal :最適な
decades-old :数十年にわたる
a non-reversible nature :非可逆的な性質
radiography :x線撮影
decline :減少
halt :停止する
extrapolate :外挿法によって推定する
controversies :論争
traits :特徴
■使いたい
Few randomised controlled trials provide high-level evidence
high-level evidence for management strategies to treat the children
the children affected by bronchiectasis
still need to be generated
小児の多発性硬化症におけるFingolimod 及び Interferon βeta-1a の比較試験
[title]
Trial of Fingolimod versus Interferon Beta-1a in Pediatric Multiple Sclerosis.
[author]
Chitnis T, et al. N Engl J Med. 2018.
Show full citation
[Abstract]
BACKGROUND: Treatment of patients younger than 18 years of age with multiple sclerosis has not been adequately examined in randomized trials. We compared fingolimod with interferon beta-1a in this population.
METHODS: In this phase 3 trial, we randomly assigned patients 10 to 17 years of age with relapsing multiple sclerosis in a 1:1 ratio to receive oral fingolimod at a dose of 0.5 mg per day (0.25 mg per day for patients with a body weight of ≤40 kg) or intramuscular interferon beta-1a at a dose of 30 μg per week for up to 2 years. The primary end point was the annualized relapse rate.
RESULTS: Of a total of 215 patients, 107 were assigned to fingolimod and 108 to interferon beta-1a. The mean age of the patients was 15.3 years. Among all patients, there was a mean of 2.4 relapses during the preceding 2 years. The adjusted annualized relapse rate was 0.12 with fingolimod and 0.67 with interferon beta-1a (absolute difference, 0.55 relapses; relative difference, 82%; P<0.001). The key secondary end point of the annualized rate of new or newly enlarged lesions on T2-weighted magnetic resonance imaging (MRI) was 4.39 with fingolimod and 9.27 with interferon beta-1a (absolute difference, 4.88 lesions; relative difference, 53%; P<0.001). Adverse events, excluding relapses of multiple sclerosis, occurred in 88.8% of patients who received fingolimod and 95.3% of those who received interferon beta-1a. Serious adverse events occurred in 18 patients (16.8%) in the fingolimod group and included seizures (in 4 patients), infection (in 4 patients), and leukopenia (in 2 patients). Serious adverse events occurred in 7 patients (6.5%) in the interferon beta-1a group and included infection (in 2 patients) and supraventricular tachycardia (in 1 patient).
CONCLUSIONS: Among pediatric patients with relapsing multiple sclerosis, fingolimod was associated with a lower rate of relapse and less accumulation of lesions on MRI over a 2-year period than interferon beta-1a but was associated with a higher rate of serious adverse events. Longer studies are required to determine the durability and safety of fingolimod in pediatric multiple sclerosis. (Funded by Novartis Pharma; PARADIG MS ClinicalTrials.gov number, NCT01892722 .).
[memo]
■知らない
Fingolimod :an immunomodulating drug, mostly used for treating multiple sclerosis (MS)
Pediatric :小児の
relapsing :再発性の
intramuscular :筋肉内の
annualized :年率の
the annualized relapse rate :一年内の再発率
a mean of :平均
preceding :先行する
Adverse events :有害事象
seizures :発作、脳卒中
leukopenia :白血球減少
supraventricular tachycardia :上室性頻拍
durability :耐久性
■使いたい
has not been adequately examined in randomized trials
in this population
was associated with a lower rate of
Mutation Clearance after Transplantation for Myelodysplastic Syndrome.
[title]
Mutation Clearance after Transplantation for Myelodysplastic Syndrome.
[author]
Duncavage EJ, et al. N Engl J Med. 2018.
Show full citation
[Abstract]
BACKGROUND: Allogeneic hematopoietic stem-cell transplantation is the only curative treatment for patients with myelodysplastic syndrome (MDS). The molecular predictors of disease progression after transplantation are unclear.
METHODS: We sequenced bone marrow and skin samples from 90 adults with MDS who underwent allogeneic hematopoietic stem-cell transplantation after a myeloablative or reduced-intensity conditioning regimen. We detected mutations before transplantation using enhanced exome sequencing, and we evaluated mutation clearance by using error-corrected sequencing to genotype mutations in bone marrow samples obtained 30 days after transplantation. In this exploratory study, we evaluated the association of a mutation detected after transplantation with disease progression and survival.
RESULTS: Sequencing identified at least one validated somatic mutation before transplantation in 86 of 90 patients (96%); 32 of these patients (37%) had at least one mutation with a maximum variant allele frequency of at least 0.5% (equivalent to 1 heterozygous mutant cell in 100 cells) 30 days after transplantation. Patients with disease progression had mutations with a higher maximum variant allele frequency at 30 days than those who did not (median maximum variant allele frequency, 0.9% vs. 0%; P<0.001). The presence of at least one mutation with a variant allele frequency of at least 0.5% at day 30 was associated with a higher risk of progression (53.1% vs. 13.0%; conditioning regimen-adjusted hazard ratio, 3.86; 95% confidence interval [CI], 1.96 to 7.62; P<0.001) and a lower 1-year rate of progression-free survival than the absence of such a mutation (31.3% vs. 59.3%; conditioning regimen-adjusted hazard ratio for progression or death, 2.22; 95% CI, 1.32 to 3.73; P=0.005). The rate of progression-free survival was lower among patients who had received a reduced-intensity conditioning regimen and had at least one persistent mutation with a variant allele frequency of at least 0.5% at day 30 than among patients with other combinations of conditioning regimen and mutation status (P≤0.001). Multivariate analysis confirmed that patients who had a mutation with a variant allele frequency of at least 0.5% detected at day 30 had a higher risk of progression (hazard ratio, 4.48; 95% CI, 2.21 to 9.08; P<0.001) and a lower 1-year rate of progression-free survival than those who did not (hazard ratio for progression or death, 2.39; 95% CI, 1.40 to 4.09; P=0.002).
CONCLUSIONS: The risk of disease progression was higher among patients with MDS in whom persistent disease-associated mutations were detected in the bone marrow 30 days after transplantation than among those in whom these mutations were not detected. (Funded by the Leukemia and Lymphoma Society and others.).
[memo]
■知らない
Clearance :除去
Myelodysplastic :骨髄異形成
allogeneic :同種異型の
hematopoietic :造血の
predictor :予測因子
progression :腫瘍が大きくなること
myeloablative :骨髄破壊的な
reduced-intensity conditioning :強度軽減移植前療法
regimen :摂取法
exploratory :診査の
evaluate :評価する
association :関連、合同、協会
validated :確認する、有効にする、の過去形
somatic mutation :体細胞突然変異
Sequencing :DNAのヌクレオチド配列決定
variant :異なる
variant allele :変異型アレル
persistent :持続的な、頑固な
■使いたい
we evaluated mutation clearance by using
equivalent to
was associated with
The risk of disease progression was higher among
those in whom these mutations were not detecte
are unclear
One-Year Outcomes after PCI Strategies in Cardiogenic Shock.
[title]
One-Year Outcomes after PCI Strategies in Cardiogenic Shock.
[author]
Thiele H, et al. N Engl J Med. 2018.
Show full citation
[Abstract]
Background Among patients with acute myocardial infarction, cardiogenic shock, and multivessel coronary artery disease, the risk of a composite of death from any cause or severe renal failure leading to renal-replacement therapy at 30 days was found to be lower with percutaneous coronary intervention (PCI) of the culprit lesion only than with immediate multivessel PCI. We evaluated clinical outcomes at 1 year. Methods We randomly assigned 706 patients to either culprit-lesion-only PCI or immediate multivessel PCI. The results for the primary end point of death or renal-replacement therapy at 30 days have been reported previously. Prespecified secondary end points at 1 year included death from any cause, recurrent myocardial infarction, repeat revascularization, rehospitalization for congestive heart failure, the composite of death or recurrent infarction, and the composite of death, recurrent infarction, or rehospitalization for heart failure. Results As reported previously, at 30 days, the primary end point had occurred in 45.9% of the patients in the culprit-lesion-only PCI group and in 55.4% in the multivessel PCI group (P=0.01). At 1 year, death had occurred in 172 of 344 patients (50.0%) in the culprit-lesion-only PCI group and in 194 of 341 patients (56.9%) in the multivessel PCI group (relative risk, 0.88; 95% confidence interval [CI], 0.76 to 1.01). The rate of recurrent infarction was 1.7% with culprit-lesion-only PCI and 2.1% with multivessel PCI (relative risk, 0.85; 95% CI, 0.29 to 2.50), and the rate of a composite of death or recurrent infarction was 50.9% and 58.4%, respectively (relative risk, 0.87; 95% CI, 0.76 to 1.00). Repeat revascularization occurred more frequently with culprit-lesion-only PCI than with multivessel PCI (in 32.3% of the patients vs. 9.4%; relative risk, 3.44; 95% CI, 2.39 to 4.95), as did rehospitalization for heart failure (5.2% vs. 1.2%; relative risk, 4.46; 95% CI, 1.53 to 13.04). Conclusions Among patients with acute myocardial infarction and cardiogenic shock, the risk of death or renal-replacement therapy at 30 days was lower with culprit-lesion-only PCI than with immediate multivessel PCI, and mortality did not differ significantly between the two groups at 1 year of follow-up. (Funded by the European Union Seventh Framework Program and others; CULPRIT-SHOCK ClinicalTrials.gov number, NCT01927549 .).
[URL]
https://www.ncbi.nlm.nih.gov/m/pubmed/30145971/?i=16&from=nejm%20AND%20hasabstract
[Memo]
■知らない
acute myocardial infarction 急性心筋梗塞
multivessel coronary artery disease 多枝冠動脈疾患
composite 複合
a composite of A or B AもしくはBの合併
renal-replacement therapy 腎代替療法
percutaneous 経皮的
culprit 犯人、原因
culprit lesion 責任病変
recurrent 再発性の
Prespecified 事前に指定された
revascularization 血管再建
congestive heart failure うっ血性心不全
conclusions 結論
■使いたい
was found to be lower with A than with B
The rate of recurrent infarction was 1.7% with culprit-lesion-only PCI and 2.1% with multivessel PCI
the two groups at 1 year of follow-up
