1、64Pract J Cardiac Cereb Pneum Vasc DisSeptember 2023,Vol.31No.9http:/论著肺癌化疗患者发生导管相关性血流感染的影响因素及其风险预测列线图模型构建郝其艳,王炜【摘要】目的探讨肺癌化疗患者发生导管相关性血流感染(CRBSI)的影响因素,构建其风险预测列线图模型并进行验证。方法选取2010年1月至2022年11月盐城市第三人民医院收治的肺癌化疗患者1 169例为研究对象,按照64的比例将其分为建模集(701例)及验证集(468例)。收集所有患者的临床资料,根据是否发生CRBSI将建模集患者分为发生组和未发生组。采用多因素Logist
2、ic回归分析探讨肺癌化疗患者发生CRBSI的影响因素;采用R 4.1.2软件包及rms程序包建立肺癌化疗患者发生CRBSI的风险预测列线图模型;采用Hosmer-Lemeshoe拟合优度检验评价该列线图模型的拟合程度;绘制校准曲线以评估该列线图模型预测建模集及验证集肺癌化疗患者发生CRBSI的效能;采用ROC曲线分析该列线图模型对建模集及验证集肺癌化疗患者发生CRBSI的预测价值。结果建模集701例肺癌化疗患者中,发生CRBSI 71例(10.13%),未发生CRBSI 630例(89.87%)。两组肿瘤分期、营养状况、有糖尿病者占比、化疗次数、有重症监护病房住院史者占比、导管维护时间延长者占
3、比、导管移动者占比、导管留置时间、穿刺次数比较,差异有统计学意义(P0.05)。多因素Logistic回归分析结果显示,糖尿病、化疗次数、重症监护病房住院史、导管维护时间延长、导管移动、导管留置时间、穿刺次数是肺癌化疗患者发生CRBSI的影响因素(P0.05)。基于多因素Logistic回归分析结果,构建肺癌化疗患者发生CRBSI的风险预测列线图模型。Hosmer-Lemeshoe拟合优度检验结果显示,在建模集中该列线图模型的拟合程度较好(2=8.905,P=0.350),在验证集中该列线图模型的拟合程度较好(2=8.693,P=0.365)。校准曲线分析结果显示,该列线图模型预测建模集和验证
4、集肺癌化疗患者的CRBSI发生率与实际发生率基本吻合。ROC曲线分析结果显示,该列线图模型预测建模集和验证集肺癌化疗患者发生CRBSI的AUC分别为0.85995%CI(0.804,0.914)、0.87695%CI(0.813,0.940)。结论糖尿病、化疗次数5次、有重症监护病房住院史、导管维护时间延长、导管移动、导管留置时间30 d、穿刺次数2次是肺癌化疗患者发生CRBSI的危险因素,基于上述因素构建的列线图模型对肺癌化疗患者发生CRBSI具有一定预测价值。【关键词】肺肿瘤;中心静脉导管;导管相关性血流感染;影响因素分析;列线图【中图分类号】R 734.2【文献标识码】ADOI:10.1
5、2114/j.issn.1008-5971.2023.00.174Influencing Factors of Catheter-Related Bloodstream Infection in Patients with Lung Cancer Undergoing Chemotherapy and Construction of Nomogram Model for Predicting Its RiskHAO Qiyan,WANG WeiDepartment of Oncology,Yancheng Third Peoples Hospital(North Hospital),Yanch
6、eng 224000,ChinaCorresponding author:WANG Wei,E-mail:【Abstract】ObjectiveTo explore the influencing factors of catheter-related bloodstream infection(CRBSI)in patients with lung cancer undergoing chemotherapy,and construct a nomogram model for predicting its risk and validate it.MethodsA total of 1 1
7、69 lung cancer patients undergoing chemotherapy admitted to Yancheng Third Peoples Hospital from January 2010 to November 2022 were selected as the research subjects.The patients were divided into modeling set(70 cases)and validation set(468 cases)in a ratio of 6:4.Clinical data of patients were col
8、lected,the patients in modeling set were divided into occurrence group and non-occurrence group based on whether CRBSI occurred.Multivariate Logistic regression analysis was used to analyze the influencing factors of CRBSI in patients with lung cancer undergoing chemotherapy.The nomogram model for p
9、redicting the risk of CRBSI in patients with lung cancer undergoing chemotherapy was constructed by using the R 4.1.2 software package and rms package.Hosmer-Lemeshoe goodness of fit test was used to evaluate the fitting degree of the nomogram model.Calibration curve was drawn to evaluate the effect
10、iveness of the nomogram model for predicting CRBSI in patients with lung cancer undergoing chemotherapy in modeling set and validation set,and the ROC curve was used to analyze the predictive value of the nomogram model for CRBSI in patients with lung cancer undergoing chemotherapy in modeling set a
11、nd validation set.基金项目:江苏省2017年度省第五期“333工程”科研项目资助(BRA2017222)作者单位:224000江苏省盐城市第三人民医院(北院)肿瘤科通信作者:王炜,E-mail:扫描二维码查看更多65实用心脑肺血管病杂志 2023年9月第31卷第9期 投稿网址:http:/ResultsAmong 701 lung cancer patients undergoing chemotherapy in the modeling set,71(10.13%)patients had CRBSI,630(89.87%)patients had no CRBSI.Th
12、ere were significant differences in tumor stage,nutritional status,the proportion of patients with diabetes,the number of chemotherapy,the proportion of patients with a history of hospitalization in intensive care unit,the proportion of patients with prolonged catheter maintenance time,the proportio
13、n of patients with catheter movement,catheter retention time,and the number of punctures between the two groups(P 0.05).Multivariate Logistic regression analysis showed that diabetes,the number of chemotherapy,history of hospitalization in intensive care unit,prolonged catheter maintenance time,cath
14、eter movement,catheter retention time,and the number of punctures were the influencing factors of CRBSI in patients with lung cancer undergoing chemotherapy(P 0.05).The nomogram model for predicting CRBSI in patients with lung cancer undergoing chemotherapy was constructed based on the results of mu
15、ltivariate Logistic regression analysis.The results of Hosmer-Lemeshoe goodness of fit test showed that the nomogram model fit well in modeling set(2=8.905,P=0.350)and in validation set(2=8.693,P=0.365).The results of calibration curve analysis showed that the incidence of CRBSI in patients with lun
16、g cancer undergoing chemotherapy predicted by the nomogram model was basically consistent with the actual incidence of CRBSI in patients with lung cancer undergoing chemotherapy in modeling set and validation set.The results of ROC curve analysis showed that the AUC of the nomogram model for predict
17、ing CRBSI in patients with lung cancer undergoing chemotherapy in modeling set and validation set was 0.859 95%CI(0.804,0.914),0.876 95%CI(0.813,0.940),respectively.ConclusionDiabetes,the number of chemotherapy 5,history of hospitalization in intensive care unit,prolonged catheter maintenance time,c
18、atheter movement,catheter retention time 30 d,and the number of punctures 2 are the risk factors of CRBSI in patients with lung cancer undergoing chemotherapy.The nomogram model constructed based on the above factors has a certain predictive value for CRBSI in patients with lung cancer undergoing ch
19、emotherapy.【Key words】Lung neoplasms;Central venous catheters;Catheter-related bloodstream infection;Root cause analysis;Nomograms肺癌是最常见的恶性肿瘤之一,其发病率和死亡率在恶性肿瘤中排名第一,并呈逐年上升趋势1。2020年,中国新发肺癌患者例数位居新发癌症患者首位,为82万例,占中国新发癌症患者总例数的17.9%;中国肺癌死亡患者例数亦位居癌症死亡患者首位,为71万例,占中国癌症死亡患者总例数的23.8%2。肺癌的发病原因和发病机制尚不清楚,给早期诊断和治疗带来
20、很多困难3。化疗是肺癌常见的辅助治疗方法,经外周置入中心静脉导管(peripherally inserted central venous catheter,PICC)因并发症少、留置时间长等优点,为肿瘤患者提供了最佳的静脉通路,应用也越来越多4-6。尽管PICC有很多优势,但越来越多的证据表明,其导管相关性血流感染(catheter-related bloodstream infection,CRBSI)发生风险较高,发生率为0.2%9.2%7。还有研究显示,CRBSI是导致医疗费用增加、住院时间延长及患者死亡的一个重要原因8。近年来,肺癌化疗患者发生CRBSI影响因素的相关研究虽有报道8,
21、但建立预测模型者较少。列线图可直观展示患者出现相应疾病的概率,利于临床快速筛选高危人群,并制定有效干预措施。本研究旨在探讨肺癌化疗患者发生CRBSI的影响因素,并建立列线图模型来预测肺癌化疗患者发生CRBSI的风险,以期为肺癌化疗患者制定个体化治疗方案提供临床依据,从而提高患者的生活质量。1对象与方法1.1研究对象采用便利抽样法,选取2010年1月至2022年11月盐城市第三人民医院收治的肺癌化疗患者1 169例为研究对象。纳入标准:(1)经影像学及病理检查确诊为肺癌;(2)接受PICC治疗;(3)年龄18岁。排除标准:(1)合并严重的多器官功能衰竭者,如心脏衰竭、肾衰竭、呼吸衰竭等;(2)存
22、在意识或精神障碍者,如昏迷或意识紊乱等;(3)由于任何原因提前拔管者;(4)PICC治疗后使用抗凝剂治疗者;(5)合并其他恶性肿瘤者。按照64的比例将患者分为建模集(701例)及验证集(468例)。建模集与验证集临床资料比较,差异无统计学意义(P0.05),见表1。本研究经盐城市第三人民医院医学伦理委员会批准。1.2资料收集收集所有患者的临床资料,包括年龄、性别、体质指数、文化程度、病理分型(包括腺癌、鳞癌、其他)、肿瘤分期、营养状况采用主观综合营养评估(subjective global assessment,SGA)法评估患者营养状态,A级为营养正常,B级为轻中度营养不良,C级为重度营养不
23、良,将B级和C级定义为营养状况差、有无糖尿病、化疗次数、重症监护病房住院史、管腔类型(单腔、双腔)、导管维护时间是否延长、是否发生导管移动、导管留置时间、穿刺次数、置管部位(贵要静脉、肘正中静脉、头静脉)。1.3CRBSI诊断标准参照血管内导管相关感染的预防和治疗指南(2007)9,符合以下一条及以上即可诊断为CRBSI:(1)1次半定量导管培养阳性,或者定量导管培养阳性,且外周静脉血培养阳性,与导管节段属于同一微生物;(2)沿导管以及外周静脉同时抽66Pract J Cardiac Cereb Pneum Vasc DisSeptember 2023,Vol.31No.9http:/血做定量
24、血培养,两者菌落计数比为951;(3)沿中心静脉导管以及外周静脉同时抽血做定性血培养,中心静脉血培养阳性出现时间较外周血培养阳性至少早2 h;(4)外周血以及导管出血部位的脓液培养均为阳性,属于同一微生物。根据是否发生CRBSI将建模集患者分为发生组和未发生组。1.4统计学方法采用SPSS 22.0统计学软件进行数据处理。计数资料以相对数表示,组间比较采用2检验;采用多因素Logistic回归分析探讨肺癌化疗患者发生CRBSI的影响因素;采用R 4.1.2软件包及rms程序包建立肺癌化疗患者发生CRBSI的风险预测列线图模型;采用Hosmer-Lemeshoe拟合优度检验评价该列线图模型的拟合
25、程度;绘制校准曲线以评估该列线图模型预测建模集及验证集肺癌化疗患者发生CRBSI的效能;采用ROC曲线分析该列线图模型对建模集及验证集肺癌化疗患者发生CRBSI的预测价值。以P0.05为差异有统计学意义。2结果2.1未发生组与发生组临床资料比较建模集701例肺癌化疗患者中,发生CRBSI 71例(10.13%),未发生CRBSI 630例(89.87%)。两组年龄、性别、体质指数、文化程度、病理分型、管腔类型、置管部位比较,差异无统计学意义(P0.05);两组肿瘤分期、营养状况、有糖尿病者占比、化疗次数、有重症监护病房住院史者占比、导管维护时间延长者占比、导管移动者占比、导管留置时间、穿刺次数
26、比较,差异有统计学意义(P0.05),见表2。2.2肺癌化疗患者发生CRBSI影响因素的多因素Logistic回归分析以建模集肺癌化疗患者是否发生CRBSI为因变量(赋值:发生=1,未发生=0),以单因素分析差异有统计学意义的变量肿瘤分期(赋值:期=0,期=1)、营养状况(赋值:正常=0,差=1)、糖尿病(赋值:无=0,有=1)、化疗次数(赋值:5次=0,5次=1)、重症监护病房住院史(赋值:无=0,有=1)、导管维护时间延长(赋值:否=0,是=1)、导管移动(赋值:否=0,是=1)、导管留置时间(赋值:30 d=0,30 d=1)、穿刺次数(赋值:1次=0,2次=1)为自变量,进行多因素Lo
27、gistic回归分析,结果显示,糖尿病、化疗次数、重症监护病房住院史、表1建模集与验证集临床资料比较n(%)Table 1Comparison of clinical data between modeling set and validation set项目建模集(n=701)验证集(n=468)2值P值年龄1.960 0.16160岁408(58.20)253(54.06)60岁293(41.80)215(45.94)性别0.552 0.457男378(53.92)242(51.71)女323(46.08)226(48.29)体质指数2.988 0.08424 kg/m2397(56.63
28、)214(51.50)24 kg/m2304(43.37)227(48.50)文化程度0.236 0.889小学及以下410(58.49)275(58.76)中学或中专164(23.40)113(24.15)大专及以上127(18.12)80(17.09)病理分型2.758 0.252腺癌380(54.21)266(56.84)鳞癌218(31.10)125(26.71)其他103(14.69)77(16.45)肿瘤分期1.466 0.226期444(63.34)280(59.83)期257(36.66)188(40.17)营养状况0.287 0.592正常411(58.63)267(57.0
29、5)差290(41.37)201(42.95)糖尿病2.475 0.116有285(40.66)212(45.30)无416(59.34)256(54.70)化疗次数0.260 0.6105次427(60.91)292(62.39)5次274(39.09)176(37.61)重症监护病房住院史0.839 0.360有133(18.97)99(21.15)无568(81.03)369(78.85)管腔类型3.131 0.077单腔300(42.80)176(37.61)双腔401(57.20)292(62.39)导管维护时间延长2.002 0.157是38(5.42)17(3.63)否663(9
30、4.58)451(96.37)导管移动2.724 0.099是405(57.77)293(62.61)否296(42.23)175(37.39)导管留置时间1.545 0.21430 d329(46.93)237(50.64)30 d372(53.07)231(49.36)(续表1)项目建模集(n=701)验证集(n=468)2值P值穿刺次数0.134 0.7141次406(57.92)266(56.84)2次295(42.08)202(43.16)置管部位4.684 0.096贵要静脉453(64.62)286(61.11)肘正中静脉198(28.25)132(28.21)头静脉50(7.1
31、3)50(10.68)67实用心脑肺血管病杂志 2023年9月第31卷第9期 投稿网址:http:/导管维护时间延长、导管移动、导管留置时间、穿刺次数是肺癌化疗患者发生CRBSI的影响因素(P0.05),见表3。2.3肺癌化疗患者发生CRBSI的风险预测列线图模型构建及验证基于多因素Logistic回归分析结果,构建肺癌化疗患者发生CRBSI的风险预测列线图模型,见图1。Hosmer-Lemeshoe拟合优度检验结果显示,在建模集中该列线图模型的拟合程度较好(2=8.905,P=0.350),在验证集中该列线图模型的拟合程度较好(2=8.693,P=0.365)。校准曲线分析结果显示,该列线图
32、模型预测建模集和验证集肺癌化疗患者的CRBSI发生率与实际发生率基本吻合,见图2、3。ROC曲线分析结果显示,该列线图模型预测建模集和验证集肺癌化疗患者发生CRBSI的AUC分别为0.85995%CI(0.804,0.914)、0.87695%CI(0.813,0.940),见图4、5。3讨论CRBSI定义为在PICC置管或拔管后48 h内出现菌血症或真菌血症伴发热10-11。如果在早期阶段对患者进行干预,可以最大限度地降低CRBSI的发生率。因此,早期了解接受PICC治疗患者发生CRBSI的危险因素,加强临床CRBSI风险管理体系建设,对改善患者预后十分重要。本研究结果显示,建模集701例肺
33、癌化疗患者中,发生CRBSI 71例,发生率为10.13%,与既往研究报道的CRBSI发生率(10.0%)基本一致12。本研究结果显示,糖尿病、化疗次数5次、有重表2未发生组与发生组临床资料比较n(%)Table 2Comparison of clinical data between non-occurrence group and occurrence group项目发生组(n=71)未发生组(n=630)2值P值年龄0.4610.49760岁44(61.97)364(57.78)60岁27(38.03)266(42.22)性别2.0600.151男44(61.97)334(53.02)女
34、27(38.03)296(46.98)体质指数0.0930.76024 kg/m239(54.93)358(56.83)24 kg/m232(45.07)272(43.17)文化程度0.4360.804小学及以下42(59.15)368(36.01)中学或中专18(23.25)146(14.29)大专及以上11(15.49)116(49.71)病理分型5.1130.078腺癌31(43.66)349(55.40)鳞癌24(33.80)194(30.79)其他16(22.54)87(13.81)肿瘤分期24.287 0.001期26(36.62)418(66.35)期45(63.38)212(3
35、3.65)营养状况20.007 0.001正常24(33.80)387(61.43)差47(66.20)243(38.57)糖尿病11.2050.001有42(59.15)243(38.57)无29(40.85)387(61.43)化疗次数21.919 0.0015次25(35.21)402(63.81)5次46(64.79)228(36.19)重症监护病房住院史7.7260.005有20(28.17)96(15.24)无51(71.83)534(84.76)管腔类型3.4910.062单腔23(32.39)277(43.97)双腔48(67.61)353(56.03)导管维护时间延长89.9
36、18 0.001是21(29.58)17(2.70)否50(70.42)613(97.30)(续表2)项目发生组(n=71)未发生组(n=630)2值P值导管移动4.0910.043是49(69.01)356(56.51)否22(30.99)274(43.49)导管留置时间13.556 0.00130 d48(67.61)281(44.60)30 d23(32.39)349(55.40)穿刺次数43.873 0.0011次15(21.13)391(62.06)2次56(78.87)239(37.94)置管部位3.9910.136贵要静脉53(74.65)400(63.49)肘正中静脉13(18
37、.31)185(29.37)头静脉5(7.04)45(7.14)表3肺癌化疗患者发生CRBSI影响因素的多因素Logistic回归分析Table 3Multivariate Logistic regression analysis of influencing factors of CRBSI in patients with lung cancer undergoing chemotherapy变量SEWald2值P值OR值95%CI糖尿病1.138 0.33411.5890.0013.120(1.621,6.007)化疗次数1.186 0.3959.0350.0033.275(1.511,
38、7.097)重症监护病房住院史 1.372 0.4509.2780.0023.942(1.631,9.527)导管维护时间延长2.512 0.46229.5140.001 12.332(4.982,30.524)导管移动1.460 0.36515.9870.0014.304(2.105,8.802)导管留置时间1.342 0.34515.0870.0013.826(1.944,7.531)穿刺次数2.276 0.36638.5860.0019.736(4.748,19.964)常量-6.806 0.610124.3250.0010.001-注:-表示无此项68Pract J Cardiac C
39、ereb Pneum Vasc DisSeptember 2023,Vol.31No.9http:/症监护病房住院史、导管维护时间延长、导管移动、导管留置时间30 d、穿刺次数2次是肺癌化疗患者发生CRBSI的危险因素。合并糖尿病等基础疾病的患者自身免疫力较低,且由于体内糖分高或氨基酸等营养物质为细菌的繁殖提供了优良的环境,其CRBSI的发生风险升高13。化疗次数5次的肺癌患者,由于长期使用化疗药物,免疫细胞遭到严重破坏及抑制,造成体内白细胞减少,免疫功能下降,杀灭局部细菌的能力变差,从而导致CRBSI的发生风险增加14。研究表明,入住重症监护病房增加了医院获得性感染的概率,从而增加CRBSI
40、的发生风险15。导管维护时间延长可能导致敷贴黏性降低、变松动,细菌大量繁殖而引起局部感染。图1肺癌化疗患者发生CRBSI的风险预测列线图模型Figure 1The nomogram model for predicting the risk of CRBSI in patients with lung cancer undergoing chemotherapy00.20.20.40.60.81.00.40.60.81.0原始曲线校准曲线理想曲线预测发生率实际发生率00.20.20.40.60.81.00.40.60.81.0原始曲线校准曲线理想曲线预测发生率实际发生率图2列线图模型预测建模集
41、肺癌化疗患者发生CRBSI的校准曲线Figure 2Calibration curve of nomogram model for predicting CRBSI in patients with lung cancer undergoing chemotherapy in modeling set图3列线图模型预测验证集肺癌化疗患者发生CRBSI的校准曲线Figure 3Calibration curve of nomogram model for predicting CRBSI in patients with lung cancer undergoing chemotherapy i
42、n validation set00.20.20.40.60.81.00.40.60.81.01-特异度灵敏度图4列线图模型预测建模集肺癌化疗患者发生CRBSI的ROC曲线Figure 4ROC curve of nomogram model for predicting CRBSI in patients with lung cancer undergoing chemotherapy in modeling set00.20.20.40.60.81.00.40.60.81.01-特异度灵敏度图5列线图模型预测验证集肺癌化疗患者发生CRBSI的ROC曲线Figure 5ROC curve o
43、f nomogram model for predicting CRBSI in patients with lung cancer undergoing chemotherapy in validation set69实用心脑肺血管病杂志 2023年9月第31卷第9期 投稿网址:http:/因此,建议加强宣教,告知患者按时维护导管的重要性。导管移动、反复穿刺会造成血管内壁、皮下组织损伤,这为细菌的侵入创造了机会,同时插管部位皮肤的定植菌可沿皮下隧道转移至静脉血管,最终导致CRBSI的发生16-17,因此管理部门应完善PICC护士的资质准入制度,确保PICC护士拥有高超的穿刺技术。此外,随着导
44、管留置时间延长,细菌大量繁殖并沿着导管表面迁移入体内,从而导致CRBSI的发生。因此,病情允许后,应尽早拔除PICC,以缩短导管留置时间或者限制导管留置时间,同时定期更换导管,以降低CRBSI发生风险。临床医护人员可根据肺癌化疗患者发生CRBSI的危险因素制定个性化干预方案,防患于未然,以期降低CRBSI的发生风险。列线图模型已被广泛用于疾病预后分析,且结果的可视化极大地提高了预测的准确性,使其更适合于临床决策18。因此,本研究基于多因素Logistic回归分析结果,构建了肺癌化疗患者发生CRBSI的风险预测列线图模型。Hosmer-Lemeshoe拟合优度检验结果显示,该列线图模型拟合程度较
45、好。校准曲线分析结果显示,该列线图模型预测肺癌化疗患者CRBSI发生率与实际发生率基本吻合。ROC曲线分析结果显示,该列线图模型预测建模集和验证集肺癌化疗患者发生CRBSI的AUC分别为0.859、0.876,提示该列线图模型对肺癌化疗患者发生CRBCI具有一定预测价值,可用于临床决策。综上所述,糖尿病、化疗次数5次、有重症监护病房住院史、导管维护时间延长、导管移动、导管留置时间30 d、穿刺次数2次是肺癌化疗患者发生CRBSI的危险因素,基于上述因素构建的列线图模型对肺癌化疗患者发生CRBSI具有一定预测价值。但本研究为单中心回顾性研究,样本量有限,今后将联合多中心并扩大样本量,以获得更准确
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