2023年3月23日 |《新英格兰医学杂志》英文音频和中英文摘要

英文音频来自NEJM官网nejm.org

1

难治性老年期抑郁症的治疗：抗抑郁药增效 vs. 换药

Antidepressant Augmentation versus Switch in Treatment-Resistant Geriatric Depression

摘 要

背景

难治性老年抑郁症患者抗抑郁药增效或换药的获益和风险尚未经过广泛研究。

Background

The benefits and risks of augmenting or switching antidepressants in older adults with treatment-resistant depression have not been extensively studied.

方法

我们开展了一项两阶段、开放标签试验，该试验纳入年龄≥60岁的难治性抑郁症患者。在第1阶段，患者按1:1:1比例随机分组，分别使用阿立哌唑将现有抗抑郁药增效，使用安非他酮将现有抗抑郁药增效或将现有抗抑郁药改用安非他酮。第1阶段未获益或不符合第1阶段纳入标准的患者在第2阶段按1:1比例随机分组，分别使用锂剂增效或改用去甲替林。每个阶段持续约10周。主要结局是心理幸福感相对于基线的变化，使用美国国立卫生研究院（National Institutes of Health）积极情绪和总体生活满意度分量表（Toolbox Positive Affect and General Life Satisfaction subscales）进行评估（人群的平均值，50；评分较高表示幸福感较强）。次要结局是抑郁症缓解。

Methods

We conducted a two-step, open-label trial involving adults 60 years of age or older with treatment-resistant depression. In step 1, patients were randomly assigned in a 1:1:1 ratio to augmentation of existing antidepressant medication with aripiprazole, augmentation with bupropion, or a switch from existing antidepressant medication to bupropion. Patients who did not benefit from or were ineligible for step 1 were randomly assigned in step 2 in a 1:1 ratio to augmentation with lithium or a switch to nortriptyline. Each step lasted approximately 10 weeks. The primary outcome was the change from baseline in psychological well-being, assessed with the National Institutes of Health Toolbox Positive Affect and General Life Satisfaction subscales (population mean, 50; higher scores indicate greater well-being). A secondary outcome was remission of depression.

结果

第1阶段共纳入619例患者；211例被分配使用阿立哌唑增效，206例使用安非他酮增效，202例改用安非他酮。幸福感评分分别提高了4.83分、4.33分和2.04分。阿立哌唑增效组与改用安非他酮组之间的差异为2.79分（95% CI，0.56~5.02；P=0.014，预设阈值P值为0.017）；阿立哌唑增效组与安非他酮增效组之间无显著差异，安非他酮增效组与改用安非他酮组之间也无显著差异。阿立哌唑增效组28.9%的患者出现缓解，安非他酮增效组为28.2%，而改用安非他酮组为19.3%。安非他酮增效组的跌倒发生率最高。第2阶段共纳入248例患者；127例被分配使用锂剂增效，121例改用去甲替林。幸福感评分分别提高了3.17分和2.18分（差异，0.99；95% CI，−1.92~3.91）。增效组18.9%的患者出现缓解，改用去甲替林组为21.5%；两组患者的跌倒发生率相似。

Result

In step 1, a total of 619 patients were enrolled; 211 were assigned to aripiprazole augmentation, 206 to bupropion augmentation, and 202 to a switch to bupropion. Well-being scores improved by 4.83 points, 4.33 points, and 2.04 points, respectively. The difference between the aripiprazole-augmentation group and the switch-to-bupropion group was 2.79 points (95% CI, 0.56 to 5.02; P=0.014, with a prespecified threshold P value of 0.017); the between-group differences were not significant for aripiprazole augmentation versus bupropion augmentation or for bupropion augmentation versus a switch to bupropion. Remission occurred in 28.9% of patients in the aripiprazole-augmentation group, 28.2% in the bupropion-augmentation group, and 19.3% in the switch-to-bupropion group. The rate of falls was highest with bupropion augmentation. In step 2, a total of 248 patients were enrolled; 127 were assigned to lithium augmentation and 121 to a switch to nortriptyline. Well-being scores improved by 3.17 points and 2.18 points, respectively (difference, 0.99; 95% CI, −1.92 to 3.91). Remission occurred in 18.9% of patients in the lithium-augmentation group and 21.5% in the switch-to-nortriptyline group; rates of falling were similar in the two groups.

结论

在难治性老年抑郁症患者中，使用阿立哌唑将现有抗抑郁药增效后，10周期间的幸福感改善幅度显著超过改用安非他酮，而且抑郁缓解率在数值上较高。在增效或改用安非他酮后治疗失败的患者中，使用锂剂增效或改用去甲替林后的幸福感变化和抑郁缓解率相似。(由以患者为中心的结局研究所[Patient-Centered Outcomes Research Institute]资助；OPTIMUM在ClinicalTrials.gov注册号为NCT02960763）。

Conclusions

In older adults with treatment-resistant depression, augmentation of existing antidepressants with aripiprazole improved well-being significantly more over 10 weeks than a switch to bupropion and was associated with a numerically higher incidence of remission. Among patients in whom augmentation or a switch to bupropion failed, changes in well-being and the occurrence of remission with lithium augmentation or a switch to nortriptyline were similar. (Funded by the; OPTIMUM ClinicalTrials.gov number, NCT02960763.)

Eric J. Lenze, Benoit H. Mulsant, Steven P. Roose,Antidepressant Augmentation versus Switch in Treatment-Resistant Geriatric Depression. DOI:10.1056/NEJMoa2204462

2

lebrikizumab治疗中重度特应性皮炎的两项3期试验

Two Phase 3 Trials of Lebrikizumab for Moderate-to-Severe Atopic Dermatitis

摘 要

背景

lebrikizumab是靶向白介素-13的高亲和力IgG4单克隆抗体，可阻止白介素-4Rα-白介素-13Rα1异二聚体受体信号复合物的形成。

Background

Lebrikizumab, a high-affinity IgG4 monoclonal antibody targeting interleukin-13, prevents the formation of the interleukin-4Rα–interleukin-13Rα1 heterodimer receptor signaling complex.

方法

我们开展了两项设计完全相同、为期52周的随机、双盲、安慰剂对照3期试验；两项试验均包括16周诱导期和36周维持期。我们以2∶1的比例将符合条件的中重度特应性皮炎患者（成人[≥18岁]和青少年[12~<18岁，体重≥40 kg]）随机分组，两组分别接受250 mg lebrikizumab（在基线时和第2周时的负荷剂量为500 mg）或安慰剂，每2周1次皮下给药。我们评估了截至第16周的诱导期结局，并在本文中报告。主要结局是研究者总体评估（Investigator’s Global Assessment，IGA）评分为0或1分（表示皮肤无病变或几乎无病变；范围，0~4分[重度疾病]），第16周时相对于基线降低（表示改善）至少2分。次要结局包括湿疹面积和严重程度指数（Eczema Area and Severity Index）评分（EASI-75应答）改善75%，以及瘙痒和瘙痒对睡眠的干扰评估。本试验还评估了安全性。

Methods

We conducted two identically designed, 52-week, randomized, double-blind, placebo-controlled, phase 3 trials; both trials included a 16-week induction period and a 36-week maintenance period. Eligible patients with moderate-to-severe atopic dermatitis (adults [≥18 years of age] and adolescents [12 to <18 years of age, weighing ≥40 kg]) were randomly assigned in a 2:1 ratio to receive either lebrikizumab at a dose of 250 mg (loading dose of 500 mg at baseline and week 2) or placebo, administered subcutaneously every 2 weeks. Outcomes for the induction period were assessed up to 16 weeks and are included in this report. The primary outcome was an Investigator’s Global Assessment (IGA) score of 0 or 1 (indicating clear or almost clear skin; range, 0 to 4 [severe disease]) with a reduction (indicating improvement) of at least 2 points from baseline at week 16. Secondary outcomes included a 75% improvement in the Eczema Area and Severity Index score (EASI-75 response) and assessments of itch and of itch interference with sleep. Safety was also assessed.

结果

在试验1中，lebrikizumab组283例患者中的43.1%和安慰剂组141例患者中的12.7%达到了主要结局（P<0.001）；EASI-75应答率分别为58.8%和16.2%（P<0.001）。在试验2中，lebrikizumab组281例患者中的33.2%和安慰剂组146例患者中的10.8%达到了主要结局（P<0.001）；EASI-75应答率分别为52.1%和18.1%（P<0.001）。lebrikizumab治疗后，瘙痒和瘙痒对睡眠的干扰指标有改善。lebrikizumab组患者的结膜炎发生率高于安慰剂组患者。诱导期的大多数不良事件为轻度或中度，未导致试验终止。

Result

In trial 1, the primary outcome was met in 43.1% of 283 patients in the lebrikizumab group and in 12.7% of 141 patients in the placebo group (P<0.001); an EASI-75 response occurred in 58.8% and 16.2%, respectively (P<0.001). In trial 2, the primary outcome was met in 33.2% of 281 patients in the lebrikizumab group and in 10.8% of 146 patients in the placebo group (P<0.001); an EASI-75 response occurred in 52.1% and 18.1%, respectively (P<0.001). Measures of itch and itch interference with sleep indicated improvement with lebrikizumab therapy. The incidence of conjunctivitis was higher among patients who received lebrikizumab than among those who received placebo. Most adverse events during the induction period were mild or moderate in severity and did not lead to trial discontinuation.

结论

在两项3期试验的诱导期， lebrikizumab治疗16周对中重度特应性皮炎青少年和成人患者有效。（由Dermira资助；ADvocate1和ADvocate2在ClinicalTrials.gov注册号分别为NCT04146363和NCT04178967）。

Conclusions

In the induction period of two phase 3 trials, 16 weeks of treatment with lebrikizumab was effective in adolescents and adults with moderate-to-severe atopic dermatitis. (Funded by Dermira; ADvocate1 and ADvocate2 ClinicalTrials.gov numbers, NCT04146363 and NCT04178967, respectively.)

Jonathan I. Silverberg, Emma Guttman-Yassky, Diamant Thaçi,Two Phase 3 Trials of Lebrikizumab for Moderate-to-Severe Atopic Dermatitis. DOI:10.1056/NEJMoa2206714

本周五 中午十二点 app和官网发布全文中译

3

饮用咖啡对非卧床成人健康状况的急性效应

Acute Effects of Coffee Consumption on Health among Ambulatory Adults

摘 要

背景

咖啡是全球范围内人们最常饮用的饮料之一，但饮用咖啡对健康状况的急性效应尚不明确。

Background

Coffee is one of the most commonly consumed beverages in the world, but the acute health effects of coffee consumption remain uncertain. 

方法

我们开展了一项前瞻性、随机、病例交叉试验，旨在评估含咖啡因咖啡对心脏异位搏动和心律失常、每日步数、睡眠分钟数和血糖水平的影响。共计100名成人佩戴了连续记录的心电图装置、腕式加速度计和连续血糖监测仪。参与者下载了用于收集地理位置数据的智能手机应用程序。我们连续14天每日向参与者发送短信，随机告知其饮用含咖啡因咖啡或避免摄入咖啡因。主要结局是每日房性期前收缩的平均次数。我们通过以下几种方式评估参与者对随机分配方案的依从性：参与者记录的实时指标、每日调查、购买咖啡收据（带日期）的报销情况以及对进咖啡店所做的虚拟监控（地理围栏）。

Methods

We conducted a prospective, randomized, case-crossover trial to examine the effects of caffeinated coffee on cardiac ectopy and arrhythmias, daily step counts, sleep minutes, and serum glucose levels. A total of 100 adults were fitted with a continuously recording electrocardiogram device, a wrist-worn accelerometer, and a continuous glucose monitor. Participants downloaded a smartphone application to collect geolocation data. We used daily text messages, sent over a period of 14 days, to randomly instruct participants to consume caffeinated coffee or avoid caffeine. The primary outcome was the mean number of daily premature atrial contractions. Adherence to the randomization assignment was assessed with the use of real-time indicators recorded by the participants, daily surveys, reimbursements for date-stamped receipts for coffee purchases, and virtual monitoring (geofencing) of coffee-shop visits.

结果

参与者平均（±SD）年龄为39±13岁；51%为女性，51%为非西班牙语裔白种人。评估结果表明，参与者对随机分配方案的依从性高。饮用含咖啡因咖啡与每日58次房性期前收缩相关，而在避免摄入咖啡因的日子，每日发生53次房性期前收缩（率比，1.09；95%置信区间[CI]，0.98~1.20；P=0.10）。饮用含咖啡因咖啡与不摄入咖啡因分别与以下情况相关：每日154次和102次室性期前收缩（率比，1.51；95% CI，1.18~1.94），每日10,646步和9665步（平均差，1058；95% CI，441~1675），每晚睡眠时间397分钟和432分钟（平均差，36；95% CI，25~47）；血糖水平95 mg/dL和96 mg/dL（平均差，－0.41；95% CI，－5.42~4.60）。

Result

The mean (±SD) age of the participants was 39±13 years; 51% were women, and 51% were non-Hispanic White. Adherence to the random assignments was assessed to be high. The consumption of caffeinated coffee was associated with 58 daily premature atrial contractions as compared with 53 daily events on days when caffeine was avoided (rate ratio, 1.09; 95% confidence interval [CI], 0.98 to 1.20; P=0.10). The consumption of caffeinated coffee as compared with no caffeine consumption was associated with 154 and 102 daily premature ventricular contractions, respectively (rate ratio, 1.51; 95% CI, 1.18 to 1.94); 10,646 and 9665 daily steps (mean difference, 1058; 95% CI, 441 to 1675); 397 and 432 minutes of nightly sleep (mean difference, 36; 95% CI, 25 to 47); and serum glucose levels of 95 mg per deciliter and 96 mg per deciliter (mean difference, −0.41; 95% CI, −5.42 to 4.60).

结论

在此项随机试验中，与避免摄入咖啡因相比，饮用含咖啡因咖啡未显著增加每日房性期前收缩次数。（由美国加州大学旧金山分校[University of California，San Francisco]和美国国立卫生研究院资助；CRAVE在ClinicalTrials.gov注册号为NCT03671759）。

Conclusions

In this randomized trial, the consumption of caffeinated coffee did not result in significantly more daily premature atrial contractions than the avoidance of caffeine. (Funded by the University of California, San Francisco, and the National Institutes of Health; CRAVE ClinicalTrials.gov number, NCT03671759.)

Gregory M. Marcus, David G. Rosenthal, Gregory Nah, Acute Effects of Coffee Consumption on Health among Ambulatory Adults. DOI:10.1056/NEJMoa2204737

本周五 中午十二点 app和官网发布全文中译

4

护理机构的Covid-19监测和居民结局

Covid-19 Surveillance Testing and Resident Outcomes in Nursing Homes

摘 要
背景尽管对专业护理机构工作人员进行广泛Covid-19监测，但关于其与护理机构居民结局的关系，证据有限。BackgroundDespite widespread adoption of surveillance testing for coronavirus disease 2019 (Covid-19) among staff members in skilled nursing facilities, evidence is limited regarding its relationship with outcomes among facility residents.
方法利用2020—2022年获得的数据，我们对13,424家专业护理机构工作人员在疫情三个时期的SARS-CoV-2检测情况进行了回顾性队列研究，三个时期分别是疫苗获批前、B.1.1.259（omicron）变异株流行前以及omicron流行期间。我们评估了在无Covid-19病例几周内的工作人员检测量和该县其他专业养老机构的检测量，以及在潜在爆发期间（定义为在无病例的2周后出现病例）的Covid-19病例和居民死亡数量。我们报告了检测量较高机构（检测量第90百分位）和较低机构（第10百分位）之间的校正后结局差异。两项主要结局是潜在爆发期间，居民中的每周累积Covid-19病例数和相关死亡人数。MethodsUsing data obtained from 2020 to 2022, we performed a retrospective cohort study of testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among staff members in 13,424 skilled nursing facilities during three pandemic periods: before vaccine approval, before the B.1.1.259 (omicron) variant wave, and during the omicron wave. We assessed staff testing volumes during weeks without Covid-19 cases relative to other skilled nursing facilities in the same county, along with Covid-19 cases and deaths among residents during potential outbreaks (defined as the occurrence of a case after 2 weeks with no cases). We reported adjusted differences in outcomes between high-testing facilities (90th percentile of test volume) and low-testing facilities (10th percentile). The two primary outcomes were the weekly cumulative number of Covid-19 cases and related deaths among residents during potential outbreaks.
结果在整个研究期间，在检测量较高机构的居民中，每100个潜在爆发期间的Covid-19病例为519.7例，而在检测量较低机构的居民中，这一数值为591.2例（校正后差异，−71.5；95%置信区间[CI]，−91.3~−51.6）。在同一时期，每100个潜在爆发期间，检测量较高机构的居民有42.7人死亡，而检测量较低机构有49.8人死亡（校正后差异，−7.1；95% CI，−11.0~−3.2）。在疫苗上市之前，每100个潜在爆发期间，检测量较高和检测量较低机构分别有759.9例和1060.2例病例（校正后差异，－300.3；95% CI，−377.1~−223.5），死亡数量分别为125.2例和166.8例（校正后差异，−41.6；95% CI，−57.8~−25.5）。在omicron流行之前，检测量较高和检测量较低机构的病例和死亡人数相似；在omicron流行期间，检测量较高机构居民中的病例较少，但两组的死亡人数相似。ResultDuring the overall study period, 519.7 cases of Covid-19 per 100 potential outbreaks were reported among residents of high-testing facilities as compared with 591.2 cases among residents of low-testing facilities (adjusted difference, −71.5; 95% confidence interval [CI], −91.3 to −51.6). During the same period, 42.7 deaths per 100 potential outbreaks occurred in high-testing facilities as compared with 49.8 deaths in low-testing facilities (adjusted difference, −7.1; 95% CI, −11.0 to −3.2). Before vaccine availability, high- and low-testing facilities had 759.9 cases and 1060.2 cases, respectively, per 100 potential outbreaks (adjusted difference, −300.3; 95% CI, −377.1 to −223.5), along with 125.2 and 166.8 deaths (adjusted difference, −41.6; 95% CI, −57.8 to −25.5). Before the omicron wave, the numbers of cases and deaths were similar in high- and low-testing facilities; during the omicron wave, high-testing facilities had fewer cases among residents, but deaths were similar in the two groups. 
结论专业护理机构工作人员加强Covid-19监测与居民中Covid-19病例和死亡人数出现有临床意义减少相关，特别是在疫苗上市之前。ConclusionsGreater surveillance testing of staff members at skilled nursing facilities was associated with clinically meaningful reductions in Covid-19 cases and deaths among residents, particularly before vaccine availability.

Gregory M. Marcus, David G. Rosenthal, Gregory Nah,Acute Effects of Coffee Consumption on Health among Ambulatory Adults. DOI:10.1056/NEJMoa2204737

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