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A Bibliometric Analysis of the Global Research on Multimorbidity in Older Adults from 2000 to 2023
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摘要:目的
分析2000—2023年老年人共病领域的国际研究趋势及前沿热点，以期为老年人共病研究提供借鉴。
方法检索Web of Science数据库，将文献类型限制为“Article”或“Review”，纳入发表时间为2000年1月1日—2023年10月24日的老年人共病相关英文文献。采用VOSviewer 1.6.18软件对文献中的内容进行提取，并绘制高产国家/地区(发文量≥30篇)、机构(发文量≥43篇)的合作网络图及高频关键词(出现频次≥74次)的共现关系时间线图。采用CiteSpace 6.1.R6软件对作者、研究机构、国家等信息进行共现和聚类分析。采用R语言“bibliometrix”包分析文献的关键词演变趋势。
结果共获得老年人共病相关文献2590篇(包括Article 2230篇、Review 360篇)。自2000年以来全球发文量快速增长，美国在该领域的发文量(35.02%，907/2590)及总被引频次(31 343次)均最多。加拿大多伦多大学的发文量最大(2.59%，67/2590)，加拿大麦克马斯特大学的Jenny Ploeg(1.24%，32/2590)是成果产出最多的作者。BMC Geriatr(3.82%，99/2590)是收录老年人共病相关文献最多的期刊。该领域高频关键词主要为“multimorbidity”“older adults”“frailty”“aging”和“polypharmacy”。
结论近年来，老年人共病研究的热点主要集中于老年人共病与衰老的关系，以及与共病相关的衰弱和多重用药方面。未来可更多围绕老年综合评估、初级卫生保健以及生活质量等内容展开研究。
Abstract:ObjectiveTo analyze the research trends and cutting-edge hot spots in the field of multimorbidity in older adults from 2000 to 2023 to provide reference for related research.
MethodsWe conducted a search in the Web of Science Core Collection database, specifically looking for articles or reviews in English on multimorbidity in older adults published between January 1, 2000 and October 24, 2023. VOSviewer 1.6.18 software was used to extract the contents in the literature and draw the cooperative network diagram of high-producing countries(≥30 articles) and institutions(≥43 articles) as well as the timeline diagram of high-frequency keywords(≥74 occurrences) co-occurrence relationship. CiteSpace 6.1.R6 software was used to co-occur and cluster analyze the information of authors, research institutions and countries. The "bibliometrix" package in R was used to analyze the evolution of keywords in the literature.
ResultsA total of 2590 documents consisting of 2230 Articles and 360 Reviews were obtained. The worldwide publication count significantly increased since 2000. Among the countries, the United States had the highest number of publications (35.02%, 907/2590) and total citations(31 343 times) in this field. The University of Toronto in Canada had the largest number of articles(2.59%, 67/2590). Jenny Ploeg of McMaster University was recognized as the most prolific author(1.24%, 32/2590). When it came to journals, BMC Geriatrics had the highest amount of literature related to multimorbidity(3.82%, 99/2590). The key areas of research in this field included multimorbidity, older adults, frailty, aging, and polypharmacy. Notably, there was growing interest in studying the relationship between multimorbidity and aging in older adults, as well as the impact of frailty and polypharmacy on multimorbidities.
ConclusionsIn recent years, research on multimorbidities in the elderly has primarily centered around examining the correlation between comorbidities and aging, as well as exploring the impact of frailty and polypharmacy on individuals with multimorbidities. Future research could delve into primary health care, comprehensive geriatric assessment for older adults with multimorbidities, and maintenance of their overall quality of life.
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Keywords:
- multimorbidity /
- older adults /
- bibliometrics /
- visual analysis /
- research hot spots /
- clinical practice
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1. 病例资料
患者女性，32岁，2023年11月因“腹胀”就诊于北京协和医院肿瘤内科，CT检查示胰腺多发囊性病变合并胰头实性肿物，肝内多发富血供占位，双肾富血供占位性病变。既往手术史：于2009年、2018年行血管母细胞瘤手术，颅内病变基因检测结果为VHL(von Hippel-Lindau)杂合突变pQ96*。家族中患者父亲确诊血管母细胞瘤，双胞胎妹妹可疑VHL综合征。结合影像学结果，考虑患者符合VHL综合征表现，累及胰腺、肾脏、脑，并出现肝脏多发转移。
为进一步评估全身各系统受累情况，患者于2023年11月11日行18F-FDG PET/CT检查，提示胰头部、肝脏、全身多发糖代谢增高骨病灶，双肾肿物，与肾实质代谢活性相近(图 1)。该患者进一步参加了北京协和医院NYCOV临床研究(伦理批号：I-23PJ753，ClinicalTrials.gov Identifier：NCT05810246)，使用68Ga-NY104 PET/CT评估VHL相关病灶。68Ga-NY104是一种新型PET示踪剂，靶向VHL-HIFα-CAⅨ轴中最下游碳酸酐酶Ⅸ (carbonic anhydrase Ⅸ, CAⅨ)靶点，理论上可以评估所有VHL突变所致的的CAⅨ高表达病灶。该患者于2023年11月14日行68Ga-NY104 PET/CT检查，显示胰头肿物、肝脏多发病灶、全身多发骨病灶、双肾占位摄取均异常增高(图 2)，提示病灶异常高表达CAⅨ；小脑可见多发CAⅨ表达病灶。后行肝脏占位穿刺，病理结果示小圆细胞巢团，考虑神经内分泌瘤(NET，G3)；免疫组织化学染色：O6-甲基鸟嘌呤-DNA甲基转移酶(O6-methylguanine-DNA-methyltransferase，MGMT)(-)，嗜铬粒蛋白A(chromogranin A，CgA)(+)，Ki-67(index约25%)，突触素(synapsin，Syn)(+), CD56(+)，P53(-)，ATRX(+)，生长抑素受体2(somatostatin receptor 2，SSTR2)(+)，胰岛素瘤相关蛋白1(insulinoma associated protein 1，INS M1)(+)，AE1/AE3(+)。
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图 1 患者18F-FDG PET/CT检查(2023.11.11)A.最大密度投影图；B.肝脏增大见多发大小不等放射性摄取增高结节及团块，部分相互融合，最大截面约15.0 cm× 7.3 cm，SUVmax=18.9，TBR=11.8(中图箭头)；胰腺多发囊性密度灶，体尾部为著，最大长径约4.0 cm；C.右侧第7后肋、T11、左侧股骨头及股骨颈见放射性摄取增高灶，部分伴骨质破坏，SUVmax=17.0，TBR=10.6(箭头)；D.双肾见多个实性结节，最大位于左肾上极，大小约2.0 cm(左图箭头)，放射性摄取与周围肾脏一致，SUVmax=2.3，TBR=1.4；SUV(standardized uptake value)：标准化摄取值；TBR(tumor to background ratio)：肿瘤背景比值(以血池作为背景摄取)Figure 1. This patient's 18F-FDG PET/CT (2023.11.11)A.maximal intensity projection image; B.the liver is enlarged with multiple nodules and masses of varying sizes showing increased radiotracer uptake, some of which are fused together, the largest cross-section being approximately 15.0 cm×7.3 cm, SUVmax=18.9, TBR=11.8 (middle arrow); multiple cystic density lesions in the pancreas, predominantly in the body and tail, with the largest being approximately 4.0 cm in length; C.increased radiotracer uptake is seen in the right 7th posterior rib, T11 vertebra, left femoral head, and femoral neck, some with bone destruction, SUVmax=17.0, TBR=10.6(arrow); D. multiple solid nodules are seen in both kidneys, the largest located at the upper pole of the left kidney, measuring approximately 2.0 cm (left arrow), with radiotracer uptake similar to the surrounding renal tissue, SUVmax=2.3, TBR=1.4; SUV: standardized uptake value; TBR: tumor to background ratio (with the blood pool as the background uptake)![]()
图 2 患者68Ga-NY104 PET/CT检查(2023.11.14)A.最大密度投影图；B.胰头可见一软组织密度肿物，放射性摄取异常增高，SUVmax=22.9，TBR=28.6(左图)；肝内可见多发放射性摄取增高的转移灶，最大者位于右叶，融合成团片状，SUVmax=12.9，TBR=16.1 (右图)；C.全身骨骼多发放射性摄取增高灶，SUVmax=14.2，TBR=17.7；D.左肾上极(左侧箭头)及右肾中部(右侧箭头)分别可见一软组织密度肿物，较大者约2.5 cm，放射性摄取增高，SUVmax=17.2，TBR=21.5(68Ga-NY104在正常肾皮质中存在生理性摄取)；E.左小脑上脚(左侧箭头)、左小脑扁桃体(右侧箭头)可见放射性摄取稍增高灶，SUVmax=5.5，TBR=6.8；SUV、TBR: 同图 1Figure 2. This patient's 68Ga-NY104 PET/CT (2023.11.14)A.maximal intensity projection image; B.a soft tissue density mass is visible in the pancreatic head with abnormally increased radiotracer uptake, SUVmax=22.9, TBR=28.6(left); Multiple metastatic lesions with increased radiotracer uptake are visible in the liver, the largest located in the right lobe, forming a confluent mass, SUVmax=12.9, TBR=16.1(right); C.multiple sites of increased radiotracer uptake in the whole skeletal system, SUVmax=14.2, TBR=17.7; D.soft tissue density masses are visible in the upper pole of the left kidney (left arrow) and the middle part of the right kidney (right arrow), the larger one approximately 2.5 cm, with increased radiotracer uptake, SUVmax=17.2, TBR=21.5(68Ga-NY104 shows physiological uptake in the normal renal cortex); E.wlightly increased radiotracer uptake is visible in the left superior cerebellar peduncle (left arrow) and the left cerebellar tonsil (right arrow), SUVmax=5.5, TBR=6.8; SUV, TBR: same as Fig. 1本例患者评估完成后, 开始替莫唑胺+卡培他滨治疗。2024年1月腹盆腔增强CT显示肝内多发转移灶部分较前缩小，中心低强化区缩小，部分病灶较前显示不清，影像学提示部分缓解，胰腺头部占位、左肾上极及右肾中部病灶、胰腺多囊性改变、大致同前。
2. 讨论
VHL综合征是一种罕见的常染色体显性遗传病，由VHL基因的胚系突变引起，发病率为1/(91 000~ 36 000)[1]。VHL基因是一种抑癌基因，位于染色体3q25-26，编码含有213个氨基酸的VHL蛋白。VHL基因突变导致VHL蛋白合成出现障碍，而VHL蛋白是一种E3泛素连接酶，介导低氧诱导因子-1(hypoxia inducible factor-1，HIF-1)的泛素化和靶蛋白降解，从而导致HIF介导的转录途径激活，包括血管内皮生长因子(vascular endothelial growth factor, VEGF)、细胞周期蛋白D1、葡萄糖转运体1和红细胞生成素等。VHL基因的胚系突变可导致多器官系统囊肿或良恶性肿瘤[如血管母细胞瘤、肾透明细胞癌(clear cell renal cell carcinoma，ccRCC)、嗜铬细胞瘤、副神经节瘤和胰腺神经内分泌肿瘤]的发生[2]。VHL综合征的主要临床表现为：血管母细胞瘤(中枢神经系统或视网膜)、肾癌、嗜铬细胞瘤、胰腺多发囊肿、神经内分泌瘤以及内淋巴囊肿瘤。当患者符合下述条件之一时可诊断为VHL综合征：(1)有明确家族史，存在以上7种肿瘤之一；(2)无家族史，出现至少2个血管母细胞瘤或1个血管母细胞瘤及上述7种肿瘤之一[3]。
中枢神经系统血管母细胞瘤是VHL综合征患者中最常见的肿瘤，也是主要致死原因，其平均发病年龄约31岁，较散发病例早约20年，病变常发生于小脑、脊髓和脑干[4]。其临床表现受肿瘤位置及其对周围神经组织的压迫程度影响，肿瘤周围囊肿较实体肿瘤更易引发颅内压增高等症状；血管母细胞瘤出血虽罕见，但可能导致严重神经功能障碍甚至死亡[3]。肾细胞癌(renal cell carcinoma, RCC)是VHL综合征患者死亡的第二大原因，VHL相关RCC呈早发和多发特点，平均发病年龄约40岁，常累及双侧肾脏，病理学特征通常表现为ccRCC，但ccRCC的进展速度相对缓慢，肿瘤直径≤3 cm时转移的概率极低[5]。VHL相关肾囊肿与普通肾囊肿性质不同，前者的囊壁和囊液中可能含有癌细胞，需进行严密随访和监测，以便及时发现并处理可能的病变[6]。胰腺神经内分泌肿瘤(pancreatic neuroendocrine neoplasm，pNEN)是VHL综合征患者胰腺病变的主要类型之一，在行影像学检查时，超过60%的VHL患者可观察到胰腺病变，其中囊性病变是最常见的类型，其发病率约为47%。值得注意的是，近15%的VHL综合征患者还伴有pNEN[7]。pNEN为富血供肿瘤，大多数生长缓慢，但具有潜在的转移风险，应根据肿瘤大小、生长快慢和基因突变类型决定处理方式。由于pNEN早期多起病隐匿，其诊疗具有极高的挑战性，患者最终确诊时多已发生转移。早发现、早治疗是延长患者生命、改善患者预后的最佳途径。
早期影像学检查对于VHL病的评估及治疗决策有着关键作用，可提示VHL综合征患者累及的系统和器官情况，评估疾病发展变化，进而辅助临床早期治疗。目前VHL诊断及随访常用的影像学检查包括MRI和CT[8-9]。关于VHL的监测，国外指南建议[10]：(1)对于无症状或病情稳定的血管母细胞瘤患者，每2年或更早进行1次MRI检查；对于进行性血管母细胞瘤或眼周囊肿扩大的患者，或担心疾病进展的患者，需进行更频繁的MRI评估。(2) 对于RCC患者，首选腹部MRI进行监测。如未发现肿瘤，每2年进行1次MRI检查；如发现肾脏肿物(直径＜3 cm)，应每3~6个月进行1次MRI检查，以确定肿瘤稳定性，若连续3次无变化则恢复至每2年1次；如发现肾脏肿物直径＞3 cm，则应转诊行进一步评估。(3)对于pNEN患者，如未发现肿瘤，每2年进行1次MRI检查；如发现pNEN病灶＜15 mm，或在2次连续扫描中稳定，则考虑每2年进行1次胰腺影像学检查；如发现pNEN病灶＞15 mm，或现有的pNEN病灶范围扩大，则应转诊行VHL相关pNEN治疗或进一步评估。此外，对于腹部病灶的评估所采用的影像学方法优先级为：增强MRI＞平扫MRI＞增强CT＞平扫CT[10]。
VHL综合征患者往往存在多器官、多种类型病灶同时存在的情况，单一检查方法或单一示踪剂的PET/CT检查无法一次性满足临床所有病灶的评估需求。此外，目前临床常用的头部增强MRI、胸腹盆增强CT存在多次扫描时间较长，以及多次CT辐射剂量暴露较高的问题。因此，改进显像手段，寻找潜在的“一站式”成像方法，辅助临床评估VHL相关病灶成为值得研究的问题。CAⅨ是碳酸酐酶家族中的一种亚型，在调节细胞外pH中发挥至关重要的作用，亦与HIF的上调直接相关[11]。CAⅨ在正常人体组织中的表达有限，使其成为分子成像和精准药物递送的理想靶点。病理研究表明，CAⅨ在VHL相关病变中均普遍表达，包括血管母细胞瘤、内淋巴囊瘤、附睾囊腺瘤、ccRCC、pNEN、嗜铬细胞瘤和囊肿，因此CAⅨ是VHL全身病灶评估的理想靶点[12]。目前99mTc-PHC-102是唯一在临床前和临床评估中均显示出良好效果的小分子放射性示踪剂[13]，但与正电子放射性示踪剂相比，使用99mTc标记的单光子示踪剂进行全身SPECT成像，具有采集时间长、图像分辨率低的问题，这限制了CAⅨ靶点示踪剂的临床应用，且不利于发现VHL综合征相关微小病灶。
而68Ga-NY104是一种新型靶向CAⅨ的小分子探针，对于CAⅨ具有较高的靶向性。前期研究发现68Ga-NY104对CAⅨ阳性ccRCC具有良好的亲和性[14]。目前正在进行中的多项针对ccRCC的临床试验(NCT05879510、NCT05879471、NCT05879497)均显示68Ga-NY104 PET/CT对于ccRCC，特别是复发转移性肾癌展现出良好性能(数据尚未发表)，具有较高的临床开发潜力，但对于VHL综合征的评估目前尚在早期探索阶段。在本例患者中，68Ga-NY104有效检测出VHL综合征相关的肾脏、胰腺、肝转移病灶及小脑病灶，进一步提示了68Ga-NY104作为“一站式”示踪剂检出VHL相关病灶的应用前景。但目前相关数据仍较少，需更大样本量的VHL综合征人群进一步验证其诊断效能。
作者贡献：张宁负责论文构思、数据分析、论文撰写；张晓辰负责文献检索、文献筛选、数据分析；何牧负责文献筛选、数据分析；康琳、曲璇、朱鸣雷负责文献检索及论文修订；孙晓红负责论文修订与审核。利益冲突：所有作者均声明不存在利益冲突 -
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图 1 2590篇老年人共病研究文献年发文量及被引频次分布情况
Figure 1. Distribution of annual publications and citation frequency of 2590 co-morbidity research literature on older adults
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图 2 发文量≥30篇的国家/地区合作网络图
注：各节点间的连线表明二者存在合作关系，连线越粗表示合作关系越强。美国所代表的红色条带宽度、与其他条带的连接宽度均最大
Figure 2. Map of cooperation network of countries/regions with ≥30 publications
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图 3 发文量居前10位的研究机构合作网络图
Figure 3. Collaborative network map of the top 10 research institutions in terms of number of publications
表 1 发文量、连接强度、被引频次居前10位的国家
Table 1 Top 10 countries in terms of number of publications, link strength and frequency of citations
序号 国家 发文量(篇) 国家 连接强度 国家 被引频次(次) 1 美国 907 英国 396 美国 31 343 2 英国 240 美国 371 英国 10099 3 加拿大 228 意大利 323 意大利 9258 4 意大利 206 西班牙 300 荷兰 7193 5 荷兰 200 荷兰 278 加拿大 7191 6 德国 191 德国 254 德国 5782 7 中国 185 澳大利亚 243 瑞典 5086 8 西班牙 184 法国 193 瑞士 4462 9 澳大利亚 183 加拿大 170 西班牙 3944 10 瑞典 105 比利时 170 澳大利亚 3693 
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表 2 发文量、被引频次及共被引频次居前10位的作者
Table 2 Top 10 authors in terms of number of publications, citation frequency and co-citation frequency
序号 作者 发文量(篇) 作者 被引频次(次) 作者 共被引频次(次) 1 Jenny Ploeg 32 Alessandra Marengoni 3491 Alessandra Marengoni 566 2 Maureen Markle-Reid 29 Laura Fratiglioni 2794 Linda P Fried 496 3 Davide L.Vetrano 29 Susan M.Smith 1419 Martin Fortin 437 4 Alessandra Marengoni 28 Graziano Onder 1186 Mary E.Charlson 425 5 Cynthia M.Boyd 22 Martin Fortin 1123 World Health Organization 400 6 Amaia Calderon-Larranaga 22 Davide L.Vetrano 997 Cynthia M.Boyd 357 7 Graziano Onder 22 Cynthia M.Boyd 972 Karen Barnett 342 8 Laura Fratiglioni 21 Jenny Ploeg 963 Mary E Tinetti 335 9 Ai Koyanagi 17 Maureen Markle-Reid 815 Martine Exterman 293 10 Kathryn Fisher 16 Emma Wallace 799 Ronald C.Kessler 273
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表 3 发文量、总连接强度、被引频次居前10位的研究机构
Table 3 Top 10 research institutions in terms of number of publications, total link strength and citation frequency
序号 机构名称 发文量(篇) 机构名称 总连接强度 机构名称 被引频次(次) 1 多伦多大学 67 卡罗林斯卡学院 164 卡罗林斯卡学院 4128 2 卡罗林斯卡学院 63 多伦多大学 135 哥伦比亚大学 3640 3 麦克马斯特大学 53 斯德哥尔摩大学 125 布雷西亚大学 3552 4 约翰斯·霍普金斯大学 51 约翰斯·霍普金斯大学 117 约翰斯·霍普金斯大学 3343 5 华盛顿大学 50 杜克大学 115 斯德哥尔摩大学 3055 6 密歇根州立大学 49 加利福尼亚大学旧金山分校 114 斯德哥尔摩老年研究中心 2830 7 杜克大学 47 布雷西亚大学 102 伦敦卫生与热带医学院 2731 8 加利福尼亚大学旧金山分校 45 哈佛医学院 100 印第安纳大学 2653 9 悉尼大学 45 圣心天主教大学 96 拉德堡德大学 2570 10 伦敦国王学院 43 斯德哥尔摩老年研究中心 94 匹兹堡大学 2134
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表 4 发文量、被引频次居前10位的期刊
Table 4 Top 10 journals in terms of number of publications and frequency of citations
序号 期刊 发文量(篇) 影响因子(JCR2022) JCR分区 共被引期刊 被引频次(次) 影响因子(JCR2022) JCR分区 1 BMC Geriatr 99 4.1 Q2 J Am Geriatr Soc 4037 6.3 Q1 2 J Am Geriatr Soc 67 6.3 Q1 J Gerontol A Biol Sci Med Sci 2164 5.1 Q2 3 BMJ Open 56 2.9 Q2 J Am Med Assoc 2144 120.7 Q1 4 Arch Gerontol Geriatr 53 4 Q2 J Clin Oncol 2105 45.4 Q1 5 J Geriatr Oncol 53 3 Q3 Lancet 1829 168.9 Q1 6 PLoS One 50 3.7 Q2 PLoS One 1815 3.7 Q2 7 Age Ageing 46 6.7 Q1 J Clin Epidemiol 1781 7.2 Q1 8 Int J Environ Res Public Health 36 NA NA New Engl J Med 1431 158.5 Q1 9 J Gerontol A Biol Sci Med Sci 34 5.1 Q2 Age Ageing 1382 6.7 Q1 10 J Am Med Dir Assoc 33 7.6 Q1 Blood 1193 20.3 Q1
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表 5 出现频次、总连接强度居前20位的关键词
Table 5 Top 20 keywords in terms of frequency of occurrenceand total link strength
序号 关键词 出现频次(次) 总连接强度 1 multimorbidity 1172 2194 2 older adults 886 1706 3 frailty 206 468 4 aging 153 301 5 polypharmacy 138 312 6 depression 137 294 7 chronic disease 134 302 8 mortality 124 261 9 geriatric assessment 83 200 10 quality of life 80 188 11 cancer 75 213 12 dementia 74 145 13 epidemiology 70 132 14 disability 68 145 15 comprehensive geriatric assessment 62 151 16 geriatrics 60 144 17 primary care 58 116 18 anxiety 54 118 19 geriatric oncology 46 123 20 geriatric 44 102
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表 6 被引频次居前15位的文献
Table 6 Top 15 cited articles
序号 作者及发表时间 文章题目 期刊名称 被引频次(次) 文章类别 1 Moussavi S等(2007年) Depression, chronic diseases, and decrements in health: results from the World Health Surveys Lancet 2586 Article 2 Kroenke K等(2009年) The PHQ-8 as a measure of current depression in the general population J Affect Disord 2575 Article 3 Marengoni A等(2011年) Aging with multimorbidity: A systematic review of the literature Ageing Res Rev 1645 Review 4 Wolff JL等(2002年) Prevalence, expenditures, and complications of multiple chronic conditions in the elderly Arch Intern Med 1480 Article 5 Diniz BS等(2013年) Late-life depression and risk of vascular dementia and Alzheimer's disease: systematic review and meta-analysis of community-based cohort studies Br J Psychiatry 763 Review 6 Repetto L等(2002年) Comprehensive geriatric assessment adds information to Eastern Cooperative Oncology Group performance status in elderly cancer patients: An Italian group for geriatric oncology study J Clin Oncol 676 Article 7 Salive ME(2013年) Multimorbidity in Older Adults Epidemiol Rev 669 Article 8 Lehnert T等(2011年) Health Care Utilization and Costs of Elderly Persons With Multiple Chronic Conditions Med Care Res Rev 468 Review 9 Hanlon P等(2018年) Frailty and pre-frailty in middle-aged and older adults and its association with multimorbidity and mortality: a prospective analysis of 493 737 UK Biobank participants Lancet Public Health 441 Article 10 Byers AL等(2010年) High Occurrence of Mood and Anxiety Disorders Among Older Adults The National Comorbidity Survey Replication Arch Gen Psychiatry 428 Article 11 Quoix E等(2011年) Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised, phase 3 trial Lancet 417 Article 12 Diederichs C等(2011年) The measurement of multiple chronic diseases--a systematic review on existing multimorbidity indices J Gerontol A Biol Sci Med Sci 413 Review 13 Smith SM等(2012年) Managing patients with multimorbidity: systematic review of interventions in primary care and community settings BMJ 396 Article 14 Björgvinsson T等(2013年) Psychometric properties of the CES-D-10 in a psychiatric sample Assessment 389 Article 15 Smith SM等(2016年) Interventions for improving outcomes in patients with multimorbidity in primary care and community settings Cochrane DatabaseSyst Rev 384 Review
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