美国的健康支出增长和多病症流行之间存在联系，但尚不为人们所理解。多病症被认为对个人的健康支出有影响，但如何拥有一种特定的额外患病对支出的影响尚不确定。此外，大多数单病症支出估算的研究很少考虑到多病症的影响。准确估算每种疾病和不同组合所涉及的支出，可以帮助决策者更有效地制定预防政策，减少国民健康支出。本研究从两个不同的角度探讨多病症和支出之间的关系：第一，量化不同疾病组合的支出；第二，评估在考虑多病症贡献的情况下单种疾病的支出发生变化（即，在其他慢性病同时存在时附加/减少的支出）。我们使用了Truven Health MarketScan Research数据库中私人索赔的数据，其中包括来自美国的1628,894名18至64岁独立的受保者，以及他们在2018年的年度住院和门诊诊断和支出。我们选择的疾病具有在全球疾病负担病因中的平均持续时间大于一年的特征。我们使用了带有随机梯度下降方法的惩罚线性回归来评估支出和多病症之间的关系，其中包括所有可能的两个或三个不同病症的疾病组合（二元组和三元组），以及每种疾病在考虑多病症后的支出。我们通过组合类型（单一、二元组和三元组）和多病症疾病类别，分解了多病症调整后的支出变化。我们定义了63种慢性病，发现56.2%的研究人口患有至少两种慢性病。大约60.1%的疾病组合具有超加性支出（例如，该组合的支出显著高于单个疾病的总和），15.7%具有加性支出，23.6%具有亚加性支出（例如，该组合的支出显著低于单个疾病的总和）。具有高估支出的相对频繁的疾病组合（更高的观察流行率）包括内分泌、代谢、血液和免疫系统疾病（EMBI疾病）、慢性肾病、贫血和血液癌症。在考虑多病症调整后的单种疾病支出方面，下列疾病的治疗费用在高方面，且观察流行率较高：慢性肾脏疾病（14,376美元[12,291至16,670美元]）、肝硬化（6,465美元[6,090至6,930美元]）、缺血性心脏病（IHD）相关心脏疾病（6,029美元[5,529至6,529美元]）和炎症性肠病（4,697美元[4,594至4,813美元]）。与未调整的单病症支出估算相比，有50种疾病在考虑到多病症后支出更高，7种疾病的差异不到5%，6种疾病调整后的支出更低。我们一直发现慢性肾脏疾病和IHD与治疗病例的高支出、高观察流行率有关，并且与其他慢性病共同存在时对支出做出了最大的贡献。在全球健康支出和尤其是美国的不断上升中，明确高流行、高支出条件和疾病组合（特别是与更大的超加性支出相关的条件）可能有助于政策制定者、保险公司和服务提供商优先考虑优先治疗并减少支出。版权所有： © 2023 Chang等。本文是一篇开放获取文章，分发在知识共享许可证下，只要原作者和出处得到适当的认可，任何人都可以无限制地使用、分发和复制这篇文章。

The rise in health spending in the United States and the prevalence of multimorbidity-having more than one chronic condition-are interlinked but not well understood. Multimorbidity is believed to have an impact on an individual's health spending, but how having one specific additional condition impacts spending is not well established. Moreover, most studies estimating spending for single diseases rarely adjust for multimorbidity. Having more accurate estimates of spending associated with each disease and different combinations could aid policymakers in designing prevention policies to more effectively reduce national health spending. This study explores the relationship between multimorbidity and spending from two distinct perspectives: (1) quantifying spending on different disease combinations; and (2) assessing how spending on a single diseases changes when we consider the contribution of multimorbidity (i.e., additional/reduced spending that could be attributed in the presence of other chronic conditions).We used data on private claims from Truven Health MarketScan Research Database, with 16,288,894 unique enrollees ages 18 to 64 from the US, and their annual inpatient and outpatient diagnoses and spending from 2018. We selected conditions that have an average duration of greater than one year among all Global Burden of Disease causes. We used penalized linear regression with stochastic gradient descent approach to assess relationship between spending and multimorbidity, including all possible disease combinations with two or three different conditions (dyads and triads) and for each condition after multimorbidity adjustment. We decomposed the change in multimorbidity-adjusted spending by the type of combination (single, dyads, and triads) and multimorbidity disease category. We defined 63 chronic conditions and observed that 56.2% of the study population had at least two chronic conditions. Approximately 60.1% of disease combinations had super-additive spending (e.g., spending for the combination was significantly greater than the sum of the individual diseases), 15.7% had additive spending, and 23.6% had sub-additive spending (e.g., spending for the combination was significantly less than the sum of the individual diseases). Relatively frequent disease combinations (higher observed prevalence) with high estimated spending were combinations that included endocrine, metabolic, blood, and immune disorders (EMBI disorders), chronic kidney disease, anemias, and blood cancers. When looking at multimorbidity-adjusted spending for single diseases, the following had the highest spending per treated patient and were among those with high observed prevalence: chronic kidney disease ($14,376 [12,291,16,670]), cirrhosis ($6,465 [6,090,6,930]), ischemic heart disease (IHD)-related heart conditions ($6,029 [5,529,6,529]), and inflammatory bowel disease ($4,697 [4,594,4,813]). Relative to unadjusted single-disease spending estimates, 50 conditions had higher spending after adjusting for multimorbidity, 7 had less than 5% difference, and 6 had lower spending after adjustment.We consistently found chronic kidney disease and IHD to be associated with high spending per treated case, high observed prevalence, and contributing the most to spending when in combination with other chronic conditions. In the midst of a surging health spending globally, and especially in the US, pinpointing high-prevalence, high-spending conditions and disease combinations, as especially conditions that are associated with larger super-additive spending, could help policymakers, insurers, and providers prioritize and design interventions to improve treatment effectiveness and reduce spending.Copyright: © 2023 Chang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.