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Article 文章

Economic Evaluation of Individualized Nutritional Support for Hospitalized Patients with Chronic Heart Failure
住院慢性心力衰竭患者个性化营养支持的经济评估

Philipp Schuetz , Suela Sulo , Stefan Walzer , Sebastian Krenberger , Zeno Stagna ,
菲利普·舒茨 , 苏埃拉·苏洛 , 斯特凡·瓦尔策 , 塞巴斯蒂安·克伦贝格 , 泽诺·斯塔尼亚 Filomena Gomes , Beat Mueller and Cory Brunton D)
菲洛梅娜·戈麦斯 ，比特·穆勒 和科里·布伦顿 D)1 Medical University Department, Kantonsspital Aarau, 5001 Aarau, Switzerland; happy.mueller@unibas.ch
瑞士阿劳市 5001 号，阿劳州医院医学大学系；happy.mueller@unibas.ch2 Medical Faculty, University of Basel, 4001 Basel, Switzerland
巴塞尔大学医学院，瑞士巴塞尔，40013 Abbott Nutrition, Chicago, IL 60045, USA; suela.sulo@abbott.com (S.S.); cory.brunton@abbott.com (C.B.)
3 艾伯特营养，伊利诺伊州芝加哥，邮政编码 60045，美国；suela.sulo@abbott.com (S.S.)；cory.brunton@abbott.com (C.B.)4 MArS Market Access & Pricing Strategy GmbH, 79576 Weil am Rhein, Germany;
4 MArS 市场准入与定价策略有限公司，79576 维尔阿姆莱因，德国；stefan.walzer@marketaccess-pricingstrategy.de (S.W.);sebastian.krenberger@marketaccess-pricingstrategy.de (S.K.)5 Health Care Management, State University Baden-Wuerttemberg, 70174 Loerrach, Germany
5 健康护理管理，巴登-符腾堡州立大学，70174 洛伊拉赫，德国6 Social Work & Health Care, University of Applied Sciences Ravensburg-Weingarten,
6 社会工作与健康护理，拉芬斯堡-温根滕应用科技大学，88250 Weingarten, Germany
88250 维恩加滕，德国7 Division of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital, Bern University
糖尿病、内分泌学、营养医学与代谢学第 7 科，伯尔尼大学因斯特医院Hospital, University of Bern, 4001 Bern, Switzerland; zeno.stanga@insel.ch
伯尔尼大学医院，瑞士伯尔尼 4001；zeno.stanga@insel.ch8 NOVA Medical School, Universidade NOVA de Lisboa, 1169-056 Lisboa, Portugal;
8 NOVA 医学院，里斯本新大学，1169-056 里斯本，葡萄牙；filomenisabel@hotmail.com* Correspondence: schuetzph@gmail.com; Fax: +41-62-838-4100
* 通信: schuetzph@gmail.com; 传真: +41-62-838-4100

Citation: Schuetz, P.; Sulo, S.; Walzer, S.; Krenberger, S.; Stagna, Z.; Gomes, F.; Mueller, B.; Brunton, C. Economic Evaluation of Individualized Nutritional Support for Hospitalized Patients with Chronic Heart Failure Nutrients 2022, 14, 1703. https:// doi.org/10.3390/nu14091703
引用：Schuetz, P.; Sulo, S.; Walzer, S.; Krenberger, S.; Stagna, Z.; Gomes, F.; Mueller, B.; Brunton, C. 住院慢性心力衰竭患者个性化营养支持的经济评估 Nutrients 2022, 14, 1703. https:// doi.org/10.3390/nu14091703
Academic Editors: Omorogieva Ojo and Amanda R. Amorim Adegboye
学术编辑：Omorogieva Ojo 和 Amanda R. Amorim Adegboye
Received: 18 March 2022 收到：2022 年 3 月 18 日
Accepted: 18 April 2022 接受日期：2022 年 4 月 18 日
Published: 20 April 2022 发布：2022 年 4 月 20 日
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Abstract 摘要

Background Malnutrition is a highly prevalent risk factor in hospitalized patients with chronic heart failure (CHF). A recent randomized trial found lower mortality and improved health outcomes when CHF patients with nutritional risk received individualized nutritional treatment. Objective To estimate the cost-effectiveness of individualized nutritional support in hospitalized patients with CHF. Methods This analysis used data from CHF patients at risk of malnutrition ( ) who were part of the Effect of Early Nutritional Therapy on Frailty, Functional Outcomes and Recovery of Undernourished Medical Inpatients Trial (EFFORT). Study patients with CHF were randomized into (i) an intervention group (individualized nutritional support to reach energy, protein, and micronutrient goals) or (ii) a control group (receiving standard hospital food). We used a Markov model with daily cycles (over a 6-month interval) to estimate hospital costs and health outcomes in the comparator groups, thus modeling cost-effectiveness ratios of nutritional interventions. Results With nutritional support, the modeled total additional cost over the 6-month interval was 15,159 Swiss Francs (SF). With an additional 5.77 life days, the overall incremental cost-effectiveness ratio for nutritional support vs. no nutritional support was 2625 SF per life day gained. In terms of complications, patients receiving nutritional support had a cost savings of 6214 SF and an additional 4.11 life days without complications, yielding an incremental cost-effectiveness ratio for avoided complications of 1513 SF per life day gained. Conclusions On the basis of a Markov model, this economic analysis found that in-hospital nutritional support for CHF patients increased life expectancy at an acceptable incremental cost-effectiveness ratio.
背景 营养不良是住院慢性心力衰竭（CHF）患者中一种高度普遍的风险因素。最近的一项随机试验发现，当有营养风险的 CHF 患者接受个性化营养治疗时，死亡率降低，健康结果改善。 目的 评估住院 CHF 患者个性化营养支持的成本效益。 方法 本分析使用了来自营养不良风险的 CHF 患者（ ）的数据，这些患者参与了早期营养治疗对虚弱、功能结果和营养不良医疗住院患者恢复影响的试验（EFFORT）。研究中的 CHF 患者被随机分为（i）干预组（个性化营养支持以达到能量、蛋白质和微量营养素目标）或（ii）对照组（接受标准医院食物）。我们使用了一个具有每日周期的马尔可夫模型（为期 6 个月）来估算对照组的医院成本和健康结果，从而建模营养干预的成本效益比。 结果 在营养支持下，模型估算的 6 个月期间的总额外成本为 15,159 瑞士法郎（SF）。 通过额外的 5.77 个生命天数，营养支持与不提供营养支持的整体增量成本效益比为每获得一个生命天数 2625 SF。在并发症方面，接受营养支持的患者节省了 6214 SF，并且额外获得了 4.11 个没有并发症的生命天数，从而避免并发症的增量成本效益比为每获得一个生命天数 1513 SF。结论 基于马尔可夫模型，这项经济分析发现，CHF 患者在医院接受营养支持可以以可接受的增量成本效益比提高预期寿命。

Keywords: economic analysis; chronic heart failure; nutritional support; clinical outcomes; cost savings
关键词：经济分析；慢性心力衰竭；营养支持；临床结果；成本节约

1. Highlights 1. 亮点

We previously reported a reduced risk for mortality and major cardiovascular events when older hospitalized patients with chronic heart failure and malnutrition received individualized nutritional interventions compared with similar patients who consumed only a usual hospital diet. In this study, we developed a Markov model of healthcare-state transitions and costs to identify the cost-savings and incremental cost-effectiveness ratios
我们之前报告了当老年住院慢性心力衰竭和营养不良的患者接受个性化营养干预时，与仅食用常规医院饮食的类似患者相比，死亡率和重大心血管事件的风险降低。在本研究中，我们开发了一个医疗状态转移和成本的马尔可夫模型，以识别成本节约和增量成本效益比。
(ICER) of nutritional intervention. With an additional 5.77 life days, the overall ICER for nutritional support vs. no nutritional support was 2625 Swiss francs per life day gained.
营养干预的增量成本效益比（ICER）。在额外获得 5.77 个生命天的情况下，营养支持与无营养支持的整体 ICER 为每获得一个生命天 2625 瑞士法郎。

2. Introduction 2. 引言

Chronic heart failure (CHF) has high clinical and economic costs worldwide given adverse health outcomes and increased healthcare resource utilization. Globally, HF cases exceed 60 million and account for nearly 10 million life-years lost to disability, with yearly costs estimated at nearly USD 350 billion [1,2]. The annual medical cost for a person with HF was estimated at more than USD 24,000 in the United States, although costs vary widely among individuals and are highest among those who are oldest and have co-morbidities [3] Since HF imposes the greatest burden on older adults [1], the incidence is increasing as the population grows and ages [4].
慢性心力衰竭（CHF）在全球范围内具有高昂的临床和经济成本，因其导致的不良健康结果和增加的医疗资源利用。全球心力衰竭病例超过 6000 万，造成近 1000 万年的残疾生命损失，年度成本估计接近 3500 亿美元[1,2]。在美国，心力衰竭患者的年医疗费用估计超过 24000 美元，尽管费用在个体之间差异很大，且在年龄较大和有合并症的患者中最高[3]。由于心力衰竭对老年人造成的负担最大[1]，随着人口的增长和老龄化，其发病率正在上升[4]。
Poor nutritional status is common among older people with HF because of multiple negative prognostic factors, such as decreased appetite and weight loss [5], impaired intestinal function [6], the presence of other comorbidities, and catabolic metabolism due to HF-related inflammation [7,8]. Malnutrition with consequent loss of muscle mass and physical functionality has been associated with increased morbidity, poorer quality of life, and worsening of CHF [9]. Nutritional strategies have long been recommended as part of treatment for CHF, but clinical studies often focus on restricting sodium intake and following specific dietary patterns for long-term cardiac health benefits, e.g., the Mediterranean and DASH diets [10,11].
老年心力衰竭患者常见营养不良状态，原因包括多种负面预后因素，如食欲减退和体重下降[5]、肠道功能受损[6]、其他合并症的存在以及因心力衰竭相关炎症导致的分解代谢[7,8]。营养不良导致的肌肉质量和身体功能丧失与发病率增加、生活质量下降以及慢性心力衰竭恶化相关[9]。营养策略长期以来被推荐作为慢性心力衰竭治疗的一部分，但临床研究通常集中在限制钠摄入和遵循特定饮食模式以获得长期心脏健康益处，例如地中海饮食和 DASH 饮食[10,11]。
Currently, many HF patients urgently need supportive nutrition care to address nutritional shortfalls and subsequent adverse consequences. Studies have reported improved health outcomes when patients with poor nutritional status receive nutritional interventions. In fact, quality improvement programs can be used across the continuum of care to enhance outcomes for people who have evidence of poor nutritional status in home-care settings, in residential nursing care [12], and during hospital admission [13-17]. An early review by Tappendan et al. found that hospital care with a focus on nutrition can reduce complication rates, length of hospital stays, readmission rates, and mortality [17]. Further, the results of a systematic review and meta-analysis of studies on hospitalized patients with malnutrition showed that nutritional interventions can significantly improve nutritional intake and reduce the risk of mortality [18]. Beyond health benefits, individualized nutritional support during and after hospitalization is also recognized as cost-saving because it spares healthcare resource utilization due to excess hospital lengths of stay, readmissions, and need for intensive care unit (ICU) admission [19-22]. In fact, the added cost of providing nutritional support is considered low, especially relative to the resultant lowered costs of hospitalization and medical treatments [20].
目前，许多心力衰竭患者迫切需要支持性营养护理，以应对营养不足及其后续的不良后果。研究报告显示，当营养状况不佳的患者接受营养干预时，健康结果有所改善。事实上，质量改进项目可以在护理的各个环节中使用，以改善在居家护理、养老院护理[12]和住院期间[13-17]有营养不良证据的人的结果。Tappendan 等人的早期回顾发现，专注于营养的医院护理可以减少并发症发生率、住院时间、再入院率和死亡率[17]。此外，对营养不良住院患者的系统评价和荟萃分析结果显示，营养干预可以显著改善营养摄入并降低死亡风险[18]。 除了健康益处，住院期间和出院后的个性化营养支持也被认为是节省成本的，因为它减少了因住院时间过长、再入院和需要重症监护病房（ICU）入院而导致的医疗资源利用[19-22]。事实上，提供营养支持的额外成本被认为是低的，尤其是与由此降低的住院和医疗治疗成本相比[20]。
We previously reported results of beneficial health outcomes of nutritional intervention for at-risk patients in Swiss hospitals—a study known as Effect of Early Nutritional Therapy on Frailty, Functional Outcomes and Recovery of Undernourished Medical Inpatients Trial (EFFORT) [23]. In this study of more than 2000 medical inpatients, we found that nutritional interventions helped poorly nourished participants meet calorie and protein goals better than usual hospital food, significantly enhancing survival. When we focused the analysis on a subpopulation of EFFORT patients with CHF, we similarly found better health outcomes for the patients who were given supportive, individualized nutritional care [24]. Specifically, CHF patients at high nutritional risk had significantly reduced risk for mortality and major cardiovascular events when they received individualized nutritional interventions rather than standard hospital food [24]. In our current economic analysis of results from these vulnerable CHF patients in EFFORT, we applied a Markov model of health outcomes to predict how nutritional support would affect costs of healthcare utilization.
我们之前报告了瑞士医院中高风险患者营养干预的有益健康结果——一项名为“早期营养治疗对虚弱、功能结果和营养不良住院患者恢复的影响试验”（EFFORT）的研究[23]。在这项涉及 2000 多名住院患者的研究中，我们发现营养干预帮助营养不良的参与者比通常的医院食物更好地达到卡路里和蛋白质目标，显著提高了生存率。当我们将分析重点放在 EFFORT 研究中患有充血性心力衰竭（CHF）的亚群体时，我们同样发现接受支持性、个性化营养护理的患者健康结果更好[24]。具体而言，高营养风险的 CHF 患者在接受个性化营养干预而非标准医院食物时，死亡和重大心血管事件的风险显著降低[24]。在我们对这些脆弱的 CHF 患者在 EFFORT 研究中的结果进行的当前经济分析中，我们应用了健康结果的马尔可夫模型来预测营养支持将如何影响医疗利用成本。

3. Methods 3. 方法

3.1. Study Design 3.1. 研究设计

This study was a secondary economic analysis of CHF patients who were part of EFFORT—a prospective, noncommercial, multicenter, randomized controlled trial. EFFORT was registered at ClinicalTrials.gov at https:/ / clinicaltrials.gov / ct2/ show /NCT02517476 (accessed on 7 August 2015) and conducted in eight Swiss hospitals. The overall objective of the original trial was to compare medical outcomes for patients at risk of malnutrition who were randomized to (i) an intervention group (individualized nutritional support to reach energy, protein, and micronutrient goals) or (ii) a control group (receiving usual hospital food).
本研究是对参与 EFFORT 的 CHF 患者进行的二次经济分析——一项前瞻性、非商业性、多中心、随机对照试验。EFFORT 在ClinicalTrials.gov上注册，网址为 https://clinicaltrials.gov/ct2/show/NCT02517476（于 2015 年 8 月 7 日访问），并在八家瑞士医院进行。原始试验的总体目标是比较随机分配到（i）干预组（个性化营养支持以达到能量、蛋白质和微量营养素目标）或（ii）对照组（接受常规医院食物）的营养不良风险患者的医疗结果。
Individualized nutritional support included screening patients for malnutrition risk on admission; dietitian-conducted nutritional assessment for patients identified to be at risk for malnutrition; individualized nutritional care plans developed by a dietitian; and implementation of the care plan with monitoring of health outcomes during hospitalization and follow-up post-discharge [23,25].
个性化营养支持包括在入院时筛查患者的营养不良风险；由营养师进行的营养评估，针对被识别为营养不良风险的患者；由营养师制定的个性化营养护理计划；以及在住院期间实施护理计划并监测健康结果，以及出院后的随访。
The rationale for the initial trial, design details, and eligibility features were previously reported [25], and the primary results of the full study were recently published [23,26], as were health outcomes in the CHF patient population [24]. The present study is based on CHF inpatients only, and it represents an analysis of healthcare costs and health outcomes in EFFORT's two comparator groups-patients who were randomized to receive individualized nutritional support (intervention group) and those who received usual hospital food (control group) [24]. EFFORT included a total of 645 patients with CHF, with 234 (36%) acutely decompensated and 411 ( ) with chronic stable HF [24].
最初试验的理由、设计细节和资格特征已在之前的报告中提到[25]，而完整研究的主要结果最近已发布[23,26]，CHF 患者群体的健康结果也已公布[24]。本研究仅基于 CHF 住院患者，分析了 EFFORT 的两个对照组的医疗成本和健康结果——随机分配接受个性化营养支持的患者（干预组）和接受常规医院食物的患者（对照组）[24]。EFFORT 共纳入 645 名 CHF 患者，其中 234 名（36%）为急性失代偿，411 名（ ）为慢性稳定心力衰竭[24]。

3.2. Health Economic Terms Used
3.2. 使用的健康经济术语

Here, we provide definitions of key health economic terms (Appendix A, Table A1) used in our report .
在这里，我们提供了报告中使用的关键健康经济术语的定义（附录 A，表 A1） 。

3.3. Description of Markov Simulation Model
3.3. 马尔可夫模拟模型的描述

We developed a Markov simulation model with daily cycles to analyze the economic impact of nutritional support in malnourished inpatients with CHF; the model reflected the perspective of Swiss health insurers. A modeling timeframe of six months ( 180 days) with five designated health states was based on findings in a recent systematic review and meta-analysis report [18]. In the present analysis, we assumed that all patients began in a stable health state-hospitalization with HF and evidence of malnutrition risk on admission (Figure 1). During hospitalization, patients could develop complications, such as myocardial infarction or arrhythmia. This complication state was modeled as an autonomous state because the probability of death is higher than for patients not experiencing in-hospital complications. Worsening CHF and complications might require transfer to the ICU. Other modeled states included discharge from the hospital and readmission for a non-elective reason. Notably, patients had different costs for care and risks of death in each state. Transition probabilities between health states were based on the outcome results for CHF patients in our full EFFORT clinical study [24]. Transition values are compiled in Table A2 of Appendix A). Raw data were taken from the original EFFORT study for the CHF population and then put manually into the simulation model via Excel.
我们开发了一个具有每日周期的马尔可夫模拟模型，以分析营养支持对充血性心力衰竭（CHF）营养不良住院患者的经济影响；该模型反映了瑞士健康保险公司的视角。模型的时间框架为六个月（180 天），设定了五个健康状态，基于最近的系统评价和荟萃分析报告的发现[18]。在本次分析中，我们假设所有患者在入院时处于稳定的健康状态——充血性心力衰竭住院并有营养不良风险的证据（图 1）。在住院期间，患者可能会出现并发症，如心肌梗死或心律失常。该并发症状态被建模为一个自主状态，因为死亡的概率高于未经历住院并发症的患者。CHF 恶化和并发症可能需要转入重症监护室（ICU）。其他建模状态包括出院和因非选择性原因再入院。值得注意的是，患者在每个状态下的护理费用和死亡风险不同。健康状态之间的转移概率基于我们完整的 EFFORT 临床研究中 CHF 患者的结果[24]。 过渡值汇编在附录 A 的表 A2 中。原始数据来自 CHF 人群的原始 EFFORT 研究，然后通过 Excel 手动输入到模拟模型中。
Figure 1. Health states of the Markov model. Light blue arrows represent patients staying within the given health state, while bright blue arrows represent transitions between states. Abbreviation: ICU, intensive care unit.
图 1. 马尔可夫模型的健康状态。浅蓝色箭头表示患者保持在给定的健康状态，而亮蓝色箭头表示状态之间的转变。缩写：ICU，重症监护室。

3.4. Patient Population 3.4. 患者人群

For the initial trial, we screened medical patients upon hospital admission for risk of malnutrition using the Nutritional Risk Screening (NRS) 2002 [29]. We included adult patients with a total NRS score points, an expected length of stay (LOS) days, and written informed consent. We excluded patients who were treated in the intensive care or surgical units, were unable to have oral intake, or were receiving long-term nutritional support on admission; patients with terminal illnesses, gastric bypass surgery, anorexia nervosa, acute pancreatitis, acute liver failure, cystic fibrosis, stem cell transplantation; and patients previously included in the trial. All patients eligible for this secondary analysis had a documented diagnosis of CHF on hospital admission, which was confirmed and validated by a complete chart review after hospital discharge. In line with the European Society of Cardiology (ESC) guidelines [29], we stratified CHF patients, according to their ejection fraction, into three groups: (1) reduced ejection fraction (HFrEF; ), (2) mid-range ejection fraction (HFmrEF; mr EF 40-49%), and (3) preserved ejection fraction (HFpEF;
在初步试验中，我们在患者入院时使用营养风险筛查（NRS）2002 对医疗患者进行营养不良风险筛查。我们纳入了总 NRS 得分为 分、预期住院天数为 天并获得书面知情同意的成年患者。我们排除了在重症监护或外科病房接受治疗的患者、无法口服进食的患者、入院时接受长期营养支持的患者；以及患有末期疾病、胃旁路手术、神经性厌食症、急性胰腺炎、急性肝衰竭、囊性纤维化、干细胞移植的患者；以及之前已纳入试验的患者。所有符合本次二次分析的患者在入院时都有 CHF 的书面诊断，且在出院后通过完整的病历审查得到了确认和验证。根据欧洲心脏病学会（ESC）指南，我们根据射血分数将 CHF 患者分为三组：（1）射血分数降低（HFrEF； ），（2）中间射血分数（HFmrEF；射血分数 40-49%），和（3）射血分数保留（HFpEF； ）。
Table A3 of Appendix A gives an overview of the main results from the initial report [24]
附录 A 的表 A3 概述了初始报告[24]的主要结果

3.5. Costs and Utilities 3.5. 成本和效用

Utility values (cost of gained effectiveness of nutritional support) were derived from a study by Schuetz et al., assuming the utility value for preventing a major cardiovascular event (MACE) was a reasonable proxy for developing a major complication (adverse event) during hospitalization [24,26]. Costs for the different health states were assumed
效用值（营养支持获得效果的成本）来源于 Schuetz 等人的研究，假设预防重大心血管事件（MACE）的效用值是住院期间发生重大并发症（不良事件）的合理代理[24,26]。不同健康状态的成本被假定为
as follows: (1) costs for nutritional inpatient support were based on the publication by Schuetz et al. 2020 [26], assuming a standard deviation of of the input value, for both in- and outpatient nutritional support; (2) costs for of post-discharge patients to continue nutritional supplements were based on cost data from the largest Swiss online pharmacy [30]; (3) costs for a heterogeneous distribution of cardiovascular events were estimated on the basis of the Swiss Disease-related Group (DRG) costs for severe arrhythmia and cardiac arrest [31]; (4) ICU costs were based on the Swiss DRG costs for an intensive care complex treatment [31]; and (5) no costs were assigned for death (Table 1).
如下：（1）营养住院支持的费用基于 Schuetz 等人 2020 年的出版物[26]，假设输入值的标准差为 ，适用于住院和门诊营养支持；（2）出院患者继续营养补充的费用基于瑞士最大的在线药房的成本数据[30]；（3）心血管事件的异质分布费用是基于瑞士疾病相关组（DRG）对严重心律失常和心脏骤停的成本估算的[31]；（4）ICU 费用基于瑞士 DRG 对重症监护复杂治疗的成本[31]；（5）死亡未分配费用（表 1）。
Table 1. Cost input values for the health economic model with monetary costs expressed in Swiss francs (SF).
表 1. 健康经济模型的成本输入值，货币成本以瑞士法郎（SF）表示。
Cost Item 成本项目

成本输入，瑞士法郎 (SF)
Cost Input,
Swiss Francs
(SF)

概率分析分布
For Probabilistic Analysis
Distribution
SD, (SF) SD，(SF) Reference 参考

营养支持 住院患者 营养支持 门诊患者
Nutritional support
inpatient
Nutritional support
outpatient
5 Gamma 伽马 1 ZRMB [30]

普通病房每日费用
Cost per day in
normal ward
5 Gamma 伽马 1 ZRMB [30]

ICU 每日费用 每个并发症的平均费用（每日）
Cost per day in ICU
Average cost per
complication (per day)
1650 Gamma 伽马 1485 BFS 2020 [32]
.

3.6. Base-Case and Cost-Effectiveness Analyses
3.6. 基本情况和成本效益分析

The primary outcomes in our model were cost-by-health-state and total cost. We calculated days in each health state and calculated utility values as the difference between the total costs of individualized nutritional support compared with no support. Because real-life findings were modeled, we did not apply any discount rates.
我们模型中的主要结果是按健康状态划分的成本和总成本。我们计算了每个健康状态的天数，并计算了个性化营养支持与无支持之间的总成本差异所得到的效用值。由于现实生活中的发现被建模，我们没有应用任何折现率。

3.7. Sensitivity Analyses
3.7. 敏感性分析

Since costs of nutritional supplements may vary in different health states and care sites, we performed a sensitivity analysis to determine whether cost savings would be maintained when the costs of nutritional supplements were 5 SF per day (lower bound), 100 SF per day (medium bound), and 1000 SF per day (upper bound).
由于营养补充剂的成本可能因不同的健康状态和护理地点而有所不同，我们进行了敏感性分析，以确定当营养补充剂的成本为每天 5 瑞士法郎（下限）、每天 100 瑞士法郎（中限）和每天 1000 瑞士法郎（上限）时，成本节省是否能够维持。
Further, we ran sensitivity analyses (1) assuming of discharged patients would continue oral nutritional support in the outpatient setting (5 SF per day, corresponding to one oral supplement per day) and (2) assuming of discharged patients would continue nutritional support in the outpatient setting ( 5 SF per day). We also analyzed the costs per life-year. Therefore, we extrapolated the data from 180 days to 365 days Finally, we investigated which costs for nutritional support would still be cost-effective at a threshold of 100,000 SF per life-year.
此外，我们进行了敏感性分析（1）假设 出院患者在门诊继续接受口服营养支持（每天 5 SF，相当于每天一个口服补充剂），以及（2）假设 出院患者在门诊继续接受营养支持（每天 5 SF）。我们还分析了每个生命年所需的成本。因此，我们将数据从 180 天推算到 365 天。最后，我们调查了在每个生命年 100,000 SF 的阈值下，哪些营养支持的成本仍然具有成本效益。
We followed the international modeling guidelines of the ISPOR SMDM Modeling Good Research Practices Task Force [33,34] and the reporting recommendations of the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement [35].
我们遵循了 ISPOR SMDM 建模良好研究实践工作组的国际建模指南[33,34]和《健康经济评估报告标准（CHEERS）》声明的报告建议[35]。

4. Results 4. 结果

4.1. Patient Outcomes 4.1. 患者结果

In the original analysis of the EFFORT trial, 645 patients had CHF (321 patients allocated to the intervention group and 324 patients allocated to the control group). Compared with patients in the control group, the 180-day mortality rate for patients who received nutritional support was significantly lower ( 85 of ) vs. 102 of ) with an adjusted hazard ratio of 0.74 ( CI: 0.55 to ) [24].
在 EFFORT 试验的原始分析中，645 名患者患有 CHF（321 名患者分配到干预组，324 名患者分配到对照组）。与对照组的患者相比，接受营养支持的患者在 180 天的死亡率显著较低（85 例对 102 例），调整后的风险比为 0.74（95% CI：0.55 至 1.00）[24]。

4.2. Base-Case Analyses of Cost-Effectiveness
4.2. 成本效益的基本案例分析

A base-case analysis summarizes our cost results (Table 2). Here, the term 'Life days' represents the number of patient days in each health state. Utility results are shown as quality-adjusted life days (QALDs), which were calculated in the model. Finally, the calculated costs for each health state are shown. The per-patient costs for in-hospital nutritional support were estimated at 679 SF (EUR 651) per patient across the patient's hospital length of stay. In terms of costs over the 6-month timeframe of the study model, hospital care averaged 229,036 SF (EUR 219,427) per patient in the intervention group versus 213,878 SF (EUR 204,905) in the control group. These totals included costs for days in the normal ward, days in the ICU, and added costs due to complications. Ongoing nutritional support in the outpatient setting amounted to 19 SF (EUR 18) in total since of the patients continued oral nutrition supplements after discharge from the hospital. Sensitivity analysis within a range of 5 SF to 1000 SF per day for nutritional supplements did not overcome the cost benefit for nutritional support at a threshold of 100,000 SF per life-year.
基准案例分析总结了我们的成本结果（表 2）。在这里，“生活天数”一词表示每个健康状态下的患者天数。效用结果以质量调整生命天数（QALD）表示，这些是在模型中计算得出的。最后，显示了每个健康状态的计算成本。住院营养支持的每位患者成本估计为 679 SF（651 欧元），这是在患者住院期间的平均值。在研究模型的 6 个月时间框架内，干预组的医院护理平均成本为 229,036 SF（219,427 欧元），而对照组为 213,878 SF（204,905 欧元）。这些总成本包括普通病房的天数、ICU 的天数以及由于并发症产生的额外费用。门诊持续营养支持的总费用为 19 SF（18 欧元），因为 名患者在出院后继续使用口服营养补充剂。营养补充剂的敏感性分析在每天 5 SF 到 1000 SF 的范围内，并未超过每生命年 100,000 SF 的营养支持成本效益阈值。
Table 2. Costs and cost differences by nutrition group over 180 days for HF patients in the EFFORT trial.
表 2. EFFORT 试验中 HF 患者在 180 天内按营养组划分的成本及成本差异。
Life Days 生活日子 Utilities 公用事业 Cost (Swiss Francs, CHF) 成本（瑞士法郎，CHF）
Cost Item 成本项目

个性化营养支持
Individualized
Nutritional
Support

个性化营养支持
Individualized
Nutritional
Support

个性化营养支持
Individualized
Nutritional
Support

无营养支持
No
Nutritional
Support
Nutrition (support) 营养（支持） 679 -
Days in normal ward 普通病房的日子 123.84 111.24 0.25 0.23 204,342 183,544
Days in ICU 重症监护室的日子 1.88 1.90 0.00 0.00 8733 8857
Complications 并发症 10.09 14.20 0.02 0.03 15,263 21,477

出院后的生活天数
Post-hospital discharge
life days
18.77 21.47 0.04 0.04 19 0
Total 总计 154.58 148.81 0.31 0.30 229,036 213,878
Difference 差异 5.77 0.02 15,159 SF 15,159 平方英尺
ICU: intensive care unit; SF: Swiss francs. Costs were rounded to the nearest whole unit. All other data were rounded to two decimal places. EUR 0.95 .
ICU：重症监护室；SF：瑞士法郎。费用四舍五入到最接近的整数。所有其他数据四舍五入到小数点后两位。 欧元 0.95。
Incremental differences in cost, life days, and the incremental cost-effectiveness ratio (ICER) were determined (Table 3). When using nutritional support, the total cost difference over the 6-month modeling interval was 15,159 SF (EUR 14,523), which was mainly driven by increased days in a normal ward ( and by cost savings due to avoided complications ( 6214 SF ). In terms of complications, patients receiving nutritional support had 4.11 more life days without complications. Given the cost savings of 6214 SF (EUR 5953) and the additional 4.11 life days, the ICER per avoided complication was 1513 SF (EUR 1450). The overall ICER for nutritional support vs. no nutritional support was 2625 SF (EUR 2515) per life day saved.
成本、生命天数和增量成本效益比（ICER）的增量差异已确定（见表 3）。在使用营养支持时，6 个月建模区间的总成本差异为 15,159 瑞士法郎（14,523 欧元），主要是由于在普通病房的住院天数增加（ ）以及因避免并发症而节省的费用（6,214 瑞士法郎）。在并发症方面，接受营养支持的患者比未接受营养支持的患者多出 4.11 天无并发症。考虑到 6,214 瑞士法郎（5,953 欧元）的成本节省和额外的 4.11 天生命天数，每避免一例并发症的 ICER 为 1,513 瑞士法郎（1,450 欧元）。营养支持与不使用营养支持的整体 ICER 为每节省一天生命天数 2,625 瑞士法郎（2,515 欧元）。
Table 3. Results for incremental differences from base-case analysis of HF patients in EFFORT.
表 3. EFFORT 中心力衰竭患者基线案例分析的增量差异结果。

营养支持的增量变化与无营养支持
Incremental
Changes for Nutritional Support vs. No
Nutritional Support
Cost Item 成本项目

成本，瑞士法郎（SF）
Cost,
Swiss Francs (SF)
Life Days 生活日子 ICER LD, SF
Day in normal ward 普通病房的一天 20,798 12.60 1650
Day in ICU 重症监护室的一天 -123 -0.03 4109
Complication (AE) 并发症 (AE) -6214 -4.11 1513
Post-hospital stay, life days
住院后，生活天数		 19 -2.70 -7
Total 总计 15,159 5.77 2625
AE: adverse event; ICER LD: incremental cost-effectiveness ratio per life day; ICU: intensive care unit; costs were rounded to the nearest full unit, and all other data were rounded to two decimal places. .
AE：不良事件；ICER LD：每生命日的增量成本效益比；ICU：重症监护室；成本四舍五入到最接近的完整单位，所有其他数据四舍五入到小数点后两位。 。

4.3. Sensitivity Analyses
4.3. 敏感性分析

Even when varying input values for sensitivity analyses, findings were consistent with the original analysis (Appendix A, Table A4). When adjusting the proportion of patients continuing nutritional support after being discharged from the hospital, no relevant increases in nutrition costs could be observed. With of patients receiving outpatient nutritional support, 47 SF (EUR 45) would have to be invested for 180 days, and 134 SF (EUR 128) would have to be invested for one year. With of patients, those costs would amount to 94 SF (EUR 90) per 180 days and 269 SF (EUR 258) per year. We also analyzed different cost input values for nutritional support and the maximum cost input to stay under a threshold of 100,000 SF per life-year. The maximum cost input would be 6755 SF (EUR 6472) if 100% of patients continued nutritional support in the outpatient setting; 7497 SF (EUR 7182) if of patients continued nutritional support as outpatients; and 8027 SF (EUR 7690) if only of patients continued nutritional support as outpatients.
即使在对敏感性分析的输入值进行变化时，结果与原始分析一致（附录 A，表 A4）。在调整出院后继续接受营养支持的患者比例时，未观察到营养成本的相关增加。当 的患者接受门诊营养支持时，需要投资 47 瑞士法郎（45 欧元）为期 180 天，投资 134 瑞士法郎（128 欧元）为期一年。当 的患者时，这些成本将为每 180 天 94 瑞士法郎（90 欧元）和每年 269 瑞士法郎（258 欧元）。我们还分析了营养支持的不同成本输入值，以及在每生命年低于 100,000 瑞士法郎的阈值下的最大成本输入。如果 100%的患者在门诊继续接受营养支持，最大成本输入将为 6755 瑞士法郎（6472 欧元）；如果 的患者在门诊继续接受营养支持，则为 7497 瑞士法郎（7182 欧元）；如果只有 的患者在门诊继续接受营养支持，则为 8027 瑞士法郎（7690 欧元）。

5. Discussion 5. 讨论

In our prior study of hospitalized CHF patients with malnutrition (or risk of malnutrition) receiving nutritional support, we reported a significantly reduced risk for mortality and major cardiovascular events compared with CHF patients who consumed the usual hospital diet [24]. Importantly, the results of our current modeling study showed that the added cost of providing nutritional support is relatively low, especially when considering the associated reduction in risk for complications and their excess costs (extended hospitalization time and more medical treatments). Altogether, the results from our present Markov healthcare cost modeling for hospitalized CHF patients showed that nutritional care (i.e., in-hospital nutritional support continued post-discharge as needed) is a cost-effective intervention. This finding underscores the benefits of routine and robust nutritional intervention for all patients hospitalized with CHF, i.e., screening patients for malnutrition or its risk when they are admitted to the hospital, then providing nutritional support according to a dietitian-recommended, individualized plan. While the focus of our study and others was on healthcare utilization and cost, we note that such cost savings occur in the context of improved patient outcomes, especially longer survival [23].
在我们之前对住院心力衰竭（CHF）患者中营养不良（或营养不良风险）接受营养支持的研究中，我们报告与食用常规医院饮食的 CHF 患者相比，死亡率和重大心血管事件的风险显著降低[24]。重要的是，我们当前建模研究的结果显示，提供营养支持的额外成本相对较低，特别是在考虑到并发症风险及其额外成本（延长住院时间和更多医疗治疗）相关的降低时。总的来说，我们目前对住院 CHF 患者的马尔可夫医疗成本建模结果表明，营养护理（即根据需要在出院后继续提供的住院营养支持）是一项具有成本效益的干预措施。这个发现强调了对所有住院 CHF 患者进行常规和强有力的营养干预的好处，即在患者入院时筛查营养不良或其风险，然后根据营养师推荐的个性化计划提供营养支持。 虽然我们和其他研究的重点是医疗保健的利用和成本，但我们注意到，这种成本节约是在改善患者结果的背景下发生的，特别是更长的生存期 [23]。
Nutrition interventions for hospitalized patients have been established as cost-effective strategies that also yield benefits in terms of better patient outcomes, especially for older adults . In terms of health economics, value is determined as outcomes relative to costs; in the value equation, the numerator is the outcome, while the denominator is the cost. Depending on the stakeholder's perspective, high value may be viewed as reduced patient morbidity and mortality, cost containment, or profitability [38]. All stakeholders recognize the value of better patient health outcomes.
住院患者的营养干预已被确立为具有成本效益的策略，这些策略在改善患者结果方面也带来了好处，尤其是对于老年人 。在健康经济学中，价值是根据结果与成本的关系来确定的；在价值方程中，分子是结果，而分母是成本。根据利益相关者的不同视角，高价值可能被视为降低患者发病率和死亡率、控制成本或盈利能力[38]。所有利益相关者都认识到改善患者健康结果的价值。
Rising healthcare expenditures necessitate the adoption of evidence-based strategies for cost containment, especially for hospital care. The strategy of improving patients nutritional status to improve health and cost outcomes is well-known and gaining evergrowing supportive evidence. In a recent systematic review, Galekop et al. identified 53 studies that analyzed the cost-effectiveness of personalized nutrition in patient care [39]. Nearly half of the analyses ( ) concluded that nutritional intervention was cost-effective, and of the incremental cost-utility ratios were cost-effective given a willingness-to-pay threshold of USD 50,000 per quality-adjusted life-year [39]. Other researchers performed a specific value analysis on the use of nutritional support therapy to lower the risk of hospitalacquired infections (HAIs), which are life-threatening and expensive to treat [40]. On the basis of decreased HAIs and the shortened length of hospital stay among patients who were critically ill or undergoing major surgery, these researchers reported that nutritional support therapy has the potential to save the United States (US) Centers for Medicare and Medicaid Services approximately USD 104 million annually [40]. A broader Medicare Claims modeling study, the Value Project of the American Society for Enteral and Parenteral Nutrition (ASPEN), projected annual cost savings from nutritional support therapy in five selected therapeutic areas-sepsis, gastrointestinal cancer, hospital-acquired infections,
不断上升的医疗支出迫使我们采用基于证据的成本控制策略，特别是在医院护理方面。改善患者营养状况以提高健康和成本结果的策略是众所周知的，并且获得了越来越多的支持性证据。在最近的一项系统评价中，Galekop 等人识别了 53 项分析个性化营养在患者护理中成本效益的研究[39]。近一半的分析（ ）得出结论，营养干预是具有成本效益的，并且在每个质量调整生命年（QALY）愿意支付 50,000 美元的阈值下， 的增量成本效用比是具有成本效益的[39]。其他研究人员对使用营养支持疗法降低医院获得性感染（HAIs）风险进行了特定价值分析，这些感染是危及生命且治疗费用昂贵的[40]。 基于重症患者或接受重大手术患者的医院感染减少和住院时间缩短，这些研究人员报告称，营养支持治疗有潜力为美国医疗保险和医疗补助服务中心每年节省约 1.04 亿美元。一项更广泛的医疗保险索赔建模研究，即美国肠内和肠外营养学会（ASPEN）的价值项目，预计在五个选定的治疗领域（脓毒症、胃肠道癌症、医院获得性感染）中，营养支持治疗每年可节省成本
surgical complications, and pancreatitis [41]. The total cost savings was estimated at USD 580 million per year [41]. Another research team conducted an economic evaluation alongside a multicenter randomized controlled clinical trial (the NOURISH Study); the study population was malnourished older patients in US hospitals [42]. Across a 90-day time horizon, nutrition therapy yielded health improvements at a cost of no more than USD 34,000 (EUR 29,800) per quality-adjusted life-year. When extending the time horizon to a patients' entire lifetime, the intervention cost only USD 524 (EUR 460) per life-year saved [42].
外科并发症和胰腺炎[41]。总成本节省估计为每年 5.8 亿美元[41]。另一个研究团队在一项多中心随机对照临床试验（NOURISH 研究）中进行了经济评估；研究人群为美国医院中的营养不良老年患者[42]。在 90 天的时间范围内，营养治疗以不超过 34,000 美元（29,800 欧元）每个质量调整生命年的成本带来了健康改善。当将时间范围延长到患者的整个生命时，干预每节省一个生命年仅需 524 美元（460 欧元）[42]。
However, disease-associated malnutrition often remains undiagnosed and untreated While medical nutritional support requires multidisciplinary awareness and care, Meehan and colleagues noted that hospital nurses are ideally positioned to play critical roles in nutrition-screening for malnutrition on patient admission to the hospital, monitoring for and addressing conditions that impede nutrition intake, and ensuring that prescribed nutritional interventions are delivered and administered or consumed [14]. Such nursing support in multidisciplinary nutrition care can contribute to better patient outcomes at lower costs [14].
然而，疾病相关的营养不良往往未被诊断和治疗。虽然医学营养支持需要多学科的意识和护理，但 Meehan 及其同事指出，医院护士在患者入院时进行营养筛查、监测和解决影响营养摄入的情况，以及确保处方营养干预措施的实施和消费方面，处于理想的位置。这样的护理支持在多学科营养护理中可以在降低成本的同时改善患者的结果。
Our economic analysis model has limitations inherent to most modeling analyses. Costs and cost savings were calculated from the perspective of the 27 hospitals included in the Gomes et al. review and meta-analysis [18]; the results may thus not be fully generalizable to other hospitals. Demographics and different levels of need for care could have influenced treatment outcomes and related costs. Populations are becoming increasingly older, and elderly patients are perceived to need more care support. However, only total costs would be influenced by this need for care. Incremental costs would remain the same, as these patients have a need for additional care independent of the nutritional intervention. In addition, concomitant and other diseases could cause additional costs and influence the outcome of CHF treatment. Further, our cost data and reported savings are calculated from the perspective of Swiss hospital payers and their reimbursement system; this model may not be generalizable to other hospitals or to the outpatient setting. The ICER of 100,000 SF used in our sensitivity analysis is hypothetical because in Switzerland, no cost-effectiveness threshold is applied in reimbursement decisions. Finally, our model uses direct costs as the main drivers of economic decision-making from the perspective of hospital administrators and payers; future models could tackle savings in cost terms important to the patients, such as faster recovery with less disability and lower loss of work productivity.
我们的经济分析模型具有大多数建模分析固有的局限性。成本和节省的费用是从 Gomes 等人回顾和荟萃分析中纳入的 27 家医院的角度计算的[18]；因此，结果可能无法完全推广到其他医院。人口统计和不同的护理需求水平可能会影响治疗结果和相关成本。人口正在逐渐老龄化，老年患者被认为需要更多的护理支持。然而，只有总成本会受到这种护理需求的影响。增量成本将保持不变，因为这些患者对额外护理的需求与营养干预无关。此外，伴随疾病和其他疾病可能会导致额外成本并影响 CHF 治疗的结果。此外，我们的成本数据和报告的节省是从瑞士医院支付者及其报销系统的角度计算的；该模型可能无法推广到其他医院或门诊环境。 我们敏感性分析中使用的 100,000 SF 的 ICER 是假设性的，因为在瑞士，报销决策中没有应用成本效益阈值。最后，我们的模型从医院管理者和支付方的角度使用直接成本作为经济决策的主要驱动因素；未来的模型可以关注对患者重要的成本节省，例如更快的康复、更少的残疾和更低的工作生产力损失。

6. Conclusions 6. 结论

This Markov-modeled economic analysis showed that in-hospital nutritional support for chronic HF patients with malnutrition was a cost-effective strategy to improve health outcomes. Compared with other more invasive procedures, nutritional support is easy to implement in hospitals and other care settings and can help protect patients from adverse events that require cost-intensive interventions, such as 21,750 SF (EUR 20,838) for a coronary bypass or 27,818 SF (EUR 26,651) for cardiac defibrillator implants [43].
这项基于马尔可夫模型的经济分析表明，对营养不良的慢性心力衰竭患者提供院内营养支持是一种具有成本效益的策略，可以改善健康结果。与其他更具侵入性的程序相比，营养支持在医院和其他护理环境中易于实施，并且可以帮助保护患者免受需要高成本干预的负面事件，例如冠状动脉旁路手术的 21,750 瑞士法郎（20,838 欧元）或心脏除颤器植入的 27,818 瑞士法郎（26,651 欧元）[43]。

6.1. Clinical Perspective
6.1. 临床视角

Given the high proportion of older people with HF and at risk of malnutrition [9,44] we anticipate that patient-specific nutritional interventions can lead to substantial reductions in healthcare costs in addition to well-recognized health and mortality benefits. The evaluation of other patient-centered outcomes, such as quality of life, should also be explored in future studies.
鉴于老年人中心力衰竭和营养不良风险的高比例[9,44]，我们预计以患者为中心的营养干预可以在公认的健康和死亡率益处之外，显著降低医疗成本。未来的研究还应探讨其他以患者为中心的结果评估，如生活质量。

6.2. Translational Outlook
6.2. 翻译前景

The significant reduction in hospital complications and the associated costs in the subgroup of HF patients with established malnutrition may be particularly relevant for policymakers. We anticipate that such findings will be confirmed and extended by randomized controlled trials that specifically enroll hospitalized patients with CHF.
在已经确诊营养不良的心力衰竭患者亚组中，医院并发症和相关费用的显著减少可能对政策制定者特别重要。我们预计，这些发现将通过专门招募住院充血性心力衰竭患者的随机对照试验得到确认和扩展。
Author Contributions: P.S.: conceptualization, investigation, funding acquisition, original draft preparation; S.S. and C.B.: conceptualization, writing-review and editing; S.W. and S.K.: formal analysis, writing-review and editing; Z.S., F.G. and B.M.: conceptualization, investigation, writingreview and editing. All authors have read and agreed to the published version of the manuscript.
作者贡献：P.S.：概念构思、调查、资金获取、原始草稿准备；S.S. 和 C.B.：概念构思、撰写审阅和编辑；S.W. 和 S.K.：正式分析、撰写审阅和编辑；Z.S.、F.G. 和 B.M.：概念构思、调查、撰写审阅和编辑。所有作者均已阅读并同意发表的手稿版本。
Funding: The initial trial was funded by the Swiss National Science Foundation (SNSF) (PP00P3_ 150531) and the Research Council of the Kantonsspital Aarau (1410.000.058 and 1410.000.044). Abbott provided a grant (HA34) to cover expenses associated with the economic analysis.
资助：初始试验由瑞士国家科学基金会（SNSF）（PP00P3_ 150531）和阿劳州立医院研究委员会（1410.000.058 和 1410.000.044）资助。雅培提供了一笔赠款（HA34）以覆盖与经济分析相关的费用。
Institutional Review Board Statement: The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board (or Ethics Committee) of Northwestern part of Switzerland (EKNZ) (protocol code 2014_001 and 15.1.2014).
机构审查委员会声明：本研究按照赫尔辛基宣言进行，并获得瑞士西北部机构审查委员会（或伦理委员会）（EKNZ）的批准（协议代码 2014_001 和 2014 年 1 月 15 日）。
Informed Consent Statement: Informed consent was obtained from all subjects involved in the study. Not applicable for economic analysis.
知情同意声明：所有参与研究的受试者均已获得知情同意。经济分析不适用。
Data Availability Statement: The data presented in this study are available on request from the corresponding author. The data are not publicly available due to privacy and ethical reasons.
数据可用性声明：本研究中呈现的数据可根据请求从通讯作者处获得。由于隐私和伦理原因，这些数据不对公众开放。
Acknowledgments: We would like to thank all participating patients and hospital staff for their support of our trial. We thank Cecilia Hofmann for her assistance with manuscript review and editing.
致谢：我们感谢所有参与的患者和医院工作人员对我们试验的支持。感谢塞西莉亚·霍夫曼对手稿审阅和编辑的帮助。
Conflicts of Interest: The initial study was investigator-initiated and supported by a grant from the Swiss National Science Foundation to P. Schuetz (SNSF Professorship, PP00P3_150531) and the Forschungsrat of the Kantonsspital Aarau (1410.000.058 and 1410.000.044). The institution of P Schuetz previously received unrestricted grant money unrelated to this project from Nestlé Health Science and Abbott Nutrition. The institution of Z. Stanga received speaking honoraria and research support from Nestlé Health Science, Abbott Nutrition, and Fresenius Kabi. S. Sulo and C. Brunton are employees and stockholders of Abbott. S. Walzer and S. Krenberger received funding for the model development by Abbott. S. Walzer has also received funding from Nestlé and Fresenius Kabi for health economic support. All other authors report no conflicts of interest.
利益冲突：初始研究由研究者发起，并获得瑞士国家科学基金会对 P. Schuetz 的资助（SNSF 教授职位，PP00P3_150531）以及阿劳州立医院研究委员会的支持（1410.000.058 和 1410.000.044）。P. Schuetz 所在机构之前曾从雀巢健康科学和雅培营养获得与本项目无关的无限制资助。Z. Stanga 所在机构从雀巢健康科学、雅培营养和费森尤斯·卡比获得了演讲酬金和研究支持。S. Sulo 和 C. Brunton 是雅培的员工和股东。S. Walzer 和 S. Krenberger 获得了雅培的模型开发资金。S. Walzer 还从雀巢和费森尤斯·卡比获得了健康经济支持的资金。所有其他作者报告没有利益冲突。
Trial registration: ClinicalTrials.gov number NCT02517476.
试验注册：ClinicalTrials.gov 编号 NCT02517476。

Appendix A 附录 A

Table A1. Definition of terms used in health economic analyses.
表 A1. 健康经济分析中使用的术语定义。
Term 术语 Definition 定义
Markov model 马尔可夫模型

马尔可夫模型用于分析随机变化的系统。在医疗保健中，马尔可夫模型假设患者从一个离散的健康状态转移到另一个状态，例如，营养不良的住院患者、合并感染的住院患者、出院患者以及非自愿再次入院的患者。在建模中，患者从一个状态过渡到另一个状态，死亡被视为一个不可逆的状态。
A Markov model is used to analyze systems that change on a random basis. Applied to healthcare, a
Markov model assumes that a patient moves from one discrete health state to another, e.g., inpatient
with malnutrition, inpatient with infectious complication, patient discharged from hospital, and
patient readmitted to hospital non-electively. In modeling, the patient transitions from one state to
another, with death as an irreversible state.
Base-case analysis 基准案例分析

基准案例分析是指在最可能或首选的假设和输入值下运行经济模型所获得的结果。
A base case analysis refers to the results obtained from running an economic model with the most
likely or preferred set of assumptions and input values.
Cost-effectiveness 成本效益

成本效益分析是一种检查干预措施的成本和健康结果的方法。它通过估算获得一个健康结果单位（例如获得的生命年或预防的死亡）所需的成本，将一种干预措施与另一种干预措施（或现状）进行比较。在医疗保健中，目标是最大化患者群体的治疗收益，同时有效利用资源，即以成本获得价值。
Cost-effectiveness analysis is a way to examine both the costs and health outcomes of an intervention.
It compares an intervention with another intervention (or the status quo) by estimating how much it
costs to gain a unit of a health outcome, such as a life-year gained or a death prevented. In healthcare,
the goal is to maximize the benefit of treatment for a patient population while using resources
efficiently, i.e., obtaining value for the cost.

增量成本效益比 (ICER)
Incremental
cost-effectiveness ratio
(ICER)

ICER 用于比较两种不同干预措施在获得效果的成本方面。ICER 通过将两种干预措施的成本差异除以它们效果的差异来计算，例如，如果治疗 A 每位患者的费用为 100，并提供 1 个质量调整生命天（QALD），而治疗 B 的费用为 1000 瑞士法郎（SF），但提供 4 个 QALD，则治疗 B 的 ICER 为 是 每个 QALD。ICER 也称为成本效用分析。
ICER is used to compare two different interventions in terms of the cost of gained effectiveness. ICER
is computed by dividing the difference in cost of two interventions by the difference of their
effectiveness, e.g., if treatment A costs 100 per patient and provides 1 quality-adjusted life day
(QALD), and treatment B costs 1000 Swiss francs (SF) but provides 4 QALDs, the ICER of treatment B
is per QALD. ICER is also called a cost-utility analysis.
Sensitivity analysis (SA)
敏感性分析 (SA)

SA 是基于当其他参数变化时，因变量发生的情况。它被视为一种“假设评估”，用于通过检查变量在假设或方法变化时受到影响的程度，来确定评估的稳健性。
SA is based on what happens to the dependent variable when other parameters change. It is
considered a "what if" evaluation, which is used to determine the robustness of an assessment by
examining the extent to which variables are affected by changes in assumptions or methods.
Table A2. Transition probabilities for the health states in the model.
表 A2. 模型中健康状态的转移概率。
Transition Probability Per Day*
每日转移概率*
Transition Phases 过渡阶段

个性化营养支持
Individualized
Nutritional Support
Distribution 分配 SD
 无营养支持
No Nutritional
Support
Distribution 分配 SD
Stable stable 稳定 稳定 0.00418 Beta 贝塔 0.00258 0.00270 Beta 贝塔 0.00206
Stable AE 稳定的 AE 0.00106 Beta 贝塔 0.00099 0.00174 Beta 贝塔 0.00150
Stable ICU 稳定的 重症监护室 0.00018 Beta 贝塔 0.00019 0.00017 Beta 贝塔 0.00019
Stable Death 稳定的 死亡 0.00171 Beta 贝塔 0.00148 0.00210 Beta 贝塔 0.00173
AE Stable AE 稳定 0.00000 Beta 贝塔 0.00000 0.00000 Beta 贝塔 0.00000
AE 0.00293 Beta 贝塔 0.00222 0.00206 Beta 贝塔 0.00174
AE ICU 0.00000 Beta 贝塔 0.00000 0.00013 Beta 贝塔 0.00016
AE Death AE 死亡 0.00493 Beta 贝塔 0.00278 0.00608 Beta 贝塔 0.00285
Stable  稳定 0.00000 Beta 贝塔 0.00000 0.00000 Beta 贝塔 0.00000
AE 0.00000 Beta 贝塔 0.00000 0.00000 Beta 贝塔 0.00000
ICU ICU 0.00508 Beta 贝塔 0.00270 0.00608 Beta 贝塔 0.00282
ICU Death ICU 死亡 0.00283 Beta 贝塔 0.00209 0.00225 Beta 贝塔 0.00184
Stable Release 稳定的 版本 0.00171 Beta 贝塔 0.00274 0.00210 Beta 贝塔 0.00279
Release Stable 发布 稳定版 0.00233 Beta 贝塔 0.00187 0.00229 Beta 贝塔 0.00185
Release Release 发布 发布 0.00592 Beta 贝塔 0.00280 0.00601 Beta 贝塔 0.00280
AE: adverse event; ICU: intensive care unit; SD: standard deviation. * Transition probabilities were calculated from day 180 relative risk. SDs were calculated on the basis of a confidence interval (Clopper-Pearson confidence interval for a binomial proportion, with https:/ / epitools.ausvet.com.au/ ciproportion; accessed on 1 Septemeber 2021).
AE：不良事件；ICU：重症监护室；SD：标准差。* 转移概率是根据第 180 天的相对风险计算的。标准差是基于 置信区间计算的（Clopper-Pearson 置信区间用于二项比例，详细信息请访问 epitools.ausvet.com.au/，访问时间为 2021 年 9 月 1 日）。
Table A3. Clinical outcomes in patients randomized to the intervention and the control group according to the original report.
表 A3. 根据原始报告，随机分配到干预组和对照组的患者临床结果。
Parameters 参数
 对照组
Control Group

干预组
Intervention Group
-Value  -值

回归分析（调整后） (95% CI 和 -值)
Regression Analysis
(Adjusted)
(95% CI and -Value)

30 天内的全因死亡率
Outcomes
All-cause mortality within
30 days
0.013 to 0.75   到 0.75

180 天内的全因死亡率
All-cause mortality within
180 days
0.19 to 0.996   到 0.996
MACE within 30 days 30 天内的 MACE
0.005 to 0.75   到 0.75

在 30 天内入院重症监护室
Admission to the intensive care
unit within 30 days
0.96 to 2.40   到 2.40

非自愿住院在 180 天内再入院 非自愿住院在 30 天内再入院
Non-elective hospital
readmission within 180 days
Non-elective hospital
readmission within 30 days
0.38 to 1.76   到 1.76
Mean length of stay (days)
平均住院天数（天）		 0.72 to 1.94   到 1.94
Data are number of events (%). Models were adjusted for initial nutritional risk screening score and study center Continuous values are expressed as means and SDs, categorical/binary values as absolute numbers and percentages. MACE: major cardiovascular events, containing myocardial infarction, stroke, and all-cause mortality.
数据为事件数量（%）。模型已根据初始营养风险筛查评分和研究中心进行了调整。连续值以均值和标准差表示，分类/二元值以绝对数和百分比表示。MACE：主要心血管事件，包括心肌梗死、中风和全因死亡率。
Table A4. Sensitivity analysis results for ICER per life-year.
表 A4. 每生命年增量成本效益比的敏感性分析结果。
of Outpatients  的门诊病人 of Outpatients  的门诊病人 of Outpatients  的门诊病人
Cost Input for Outpatient Nutritional Support in Swiss Francs (SF)
门诊营养支持的成本输入（瑞士法郎 SF）
5 SF 2131 SF 2135 SF 2142 SF
100 SF 3290 SF 3290 平方英尺 3376 SF 3376 平方英尺 3519 SF
1000 SF 1000 平方英尺 14,269 SF 14,269 平方英尺 15,131 SF 15,131 平方英尺 16,566 SF 16,566 平方英尺

最大输入保持在 之下
Maximum input
remain below

100,000/成本-效益阈值
100,000/cost-
effectiveness
threshold
8027 SF 7497 SF 6755 SF
ICER incremental cost-effectiveness ratio; costs were rounded to the full amount. SF EUR 0.95 .
ICER 增量成本效益比；成本已四舍五入到整数。SF 欧元 0.95。

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