With great interest we read the recent article by Orwelius et al. [1] on the impact of comorbidities on health-related quality of life (HRQoL) in ICU survivors. We commend the authors for their work on addressing this challenging topic and for providing an insightful review. While we agree with the key issues highlighted by the authors, we believe that several points warrant further discussion.

One of the major challenges in assessing the impact of comorbidities on HRQoL among ICU survivors is obtaining accurate comorbidity prevalence data, both at ICU admission and during post-ICU follow-up. ICU physicians rely on medical records to identify patient comorbidities; however, conditions such as hypertension, diabetes, and chronic kidney disease (CKD) frequently remain undiagnosed until they reach advanced stages. For instance, elevated glucose levels are commonly found in patients admitted to the ICU, despite having no medical history of diabetes. While this is typically attributed to critical illness, it may also be partly due to underlying diabetes or prediabetes. Similarly, baseline serum creatinine levels are often unknown upon ICU admission. As a result, elevated creatinine levels may be misinterpreted as acute kidney injury when it could partly stem from pre-existing CKD. Our recent findings underscore this issue, revealing that while 17% of hospitalized COVID-19 patients had a medical history of CKD, 93% exhibited renal histopathological features consistent with the disease [2]. Hence, the underdiagnosis of chronic conditions can lead to an underestimation of the true burden and severity of comorbidities in patients admitted to the ICU. Consequently, the impact of these conditions on HRQoL might be inaccurately attributed solely to ICU stay when, in reality, pre-existing but undiagnosed conditions play a substantial role.

In addition, there are notable sex differences in the reporting and management of chronic health issues. Men and women may experience and report comorbidities differently and may also have different health-seeking behaviors [3]. Women, for instance, are more likely to seek medical care and thus may have their chronic conditions diagnosed earlier and managed more effectively than men. This disparity can lead to biased data regarding the prevalence and impact of comorbidities on HRQoL.

Similar to the observations of Orwelius et al., we emphasize that using age adjustment in HRQoL studies to account for comorbidities is insufficient. In recent years, there has been a noticeable shift in the age at which comorbidities are being diagnosed, with younger populations increasingly exhibiting chronic diseases traditionally associated with older adults. This trend is largely due to unhealthy lifestyle choices prevalent in modern society, such as poor dietary habits, physical inactivity, and elevated stress levels. Consequently, conditions such as hypertension, type 2 diabetes, and liver disease are now being diagnosed in younger individuals, highlighting the need for more nuanced approaches to HRQoL research.

It is well documented that critical illness can often lead to chronic conditions post-ICU, such as progression from acute kidney injury to chronic kidney disease [4, 5]. Increasing evidence suggests that other chronic diseases, like diabetes, may also develop following an ICU stay [6, 7]; however, this phenomenon remains understudied. This research gap is partly due to the lack of structured and accurate diagnosis of chronic disease and their severity at ICU admission and during post-ICU follow-up. New-onset chronic disease or exacerbation of pre-existing conditions will undoubtedly have a significant impact on HRQoL. Therefore, early identification of chronic disease will lead to more effective management strategies, improve patient recovery, and ultimately HRQoL, as well as reduce the burden on healthcare systems.

The review by Orwelius et al., importantly underscores the necessity for standardized, comprehensive approaches to comorbidity assessment in future research. The heterogeneity in HRQoL measurement tools and follow-up durations across the studies reviewed makes it challenging to draw definitive conclusions about the true impact of comorbidities versus the ICU stay itself. For instance, the use of different tools, such as SF-36, EQ-5D, and others, each with their own strengths and limitations, leads to variability in the reported outcomes. Furthermore, the absence of control groups adequately matched for undiagnosed and likely uncontrolled or early stage comorbidities limits the ability to isolate the specific effects of ICU stay on HRQoL. Moreover, the impact of non-ICU-related factors on HRQoL is usually overlooked, with potential unmeasured confounders existing, regardless of ICU admission. A standardized approach to measuring HRQoL, coupled with thorough and consistent comorbidity assessments that may require laboratory tests, would enhance the comparability and reliability of future studies.

In conclusion, addressing inaccuracies in comorbidity prevalence data, considering sex differences in health reporting and management, and adopting standardized HRQoL assessment methods are crucial. Moreover, implementing laboratory assessments of blood and/or urine samples to accurately identify comorbidities at ICU admission and during post-ICU follow-up is essential. Future research must incorporate these measures to provide a more accurate and comprehensive understanding of comorbidities and other factors influencing HRQoL in ICU survivors.

Not applicable.

ICU:

Intensive care unit

HRQoL:

Health related quality of life

CKD:

Chronic kidney disease

SF-36:

Short form 36 questions

EQ-5D:

EuroQol 5 dimensions

1. Orwelius L, Wilhelms S, Sjöberg F. Is comorbidity alone responsible for changes in health-related quality of life among critical care survivors? A purpose-specific review. Crit Care. 2024;28:208.

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2. Volbeda M, Jou-Valencia D, van den Heuvel MC, Moser J, van Meurs M, Franssen CFM. Letter regarding “association between CKD, obesity, cardiometabolic risk factors, and severe COVID-19 outcomes.” Kidney Int Rep. 2023;8:1899–900.

   Article PubMed PubMed Central Google Scholar

3. Thompson AE, Anisimowicz Y, Miedema B, Hogg W, Wodchis WP, Aubrey-Bassler K. The influence of gender and other patient characteristics on health care-seeking behaviour: a QUALICOPC study. BMC Fam Pract. 2016;17:38.

   Article PubMed PubMed Central Google Scholar

4. See EJ, Jayasinghe K, Glassford N, Bailey M, Johnson DW, Polkinghorne KR, et al. Long-term risk of adverse outcomes after acute kidney injury: a systematic review and meta-analysis of cohort studies using consensus definitions of exposure. Kidney Int. 2019;95:160–72.

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5. Fiorentino M, Grandaliano G, Gesualdo L, Castellano G. Acute kidney injury to chronic kidney disease transition. Acute Kidney Injury Basic Res Clin Pract. 2018;193:45–54.

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6. Ali Abdelhamid Y, Kar P, Finnis ME, Phillips LK, Plummer MP, Shaw JE, et al. Stress hyperglycaemia in critically ill patients and the subsequent risk of diabetes: a systematic review and meta-analysis. Crit Care. 2016;20:1–9.

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7. Jivanji CJ, Asrani VM, Windsor JA, Petrov MS. New-onset diabetes after acute and critical illness: a systematic review. Mayo Clin Proc. 2017;92:762–73.

   Article PubMed Google Scholar

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Authors and Affiliations

1. Department of Critical Care, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

   Jill Moser, Roos Mensink, Marisa Onrust, Fredrike Blokzijl & Jacqueline Koeze

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Contributions

JM wrote the manuscript. RM, MO, FB and JK provided valuable input and edited the manuscript. All authors approved the final version of the manuscript prior to submission.

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Correspondence to Jill Moser.

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Moser, J., Mensink, R., Onrust, M. et al. Unveiling the hidden burden: the impact of undiagnosed comorbidities on health-related quality of life in ICU survivors. Crit Care 28, 229 (2024). https://doi.org/10.1186/s13054-024-05025-8

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• Received: 04 July 2024

• Accepted: 06 July 2024

• Published: 10 July 2024

• DOI: https://doi.org/10.1186/s13054-024-05025-8

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我们怀着极大的兴趣阅读了 Orwelius 等人最近发表的文章。 [1] 合并症对 ICU 幸存者健康相关生活质量 (HRQoL) 的影响。我们赞扬作者为解决这一具有挑战性的主题所做的工作并提供了富有洞察力的评论。虽然我们同意作者强调的关键问题，但我们认为有几点值得进一步讨论。

评估 ICU 幸存者合并症对 HRQoL 的影响的主要挑战之一是在 ICU 入院时和 ICU 术后随访期间获取准确的合并症患病率数据。 ICU 医生依靠医疗记录来识别患者的合并症；然而，高血压、糖尿病和慢性肾病 (CKD) 等疾病往往在发展到晚期时才得到诊断。例如，尽管没有糖尿病病史，但入住 ICU 的患者通常会发现血糖水平升高。虽然这通常归因于危重疾病，但也可能部分归因于潜在的糖尿病或糖尿病前期。同样，入住 ICU 时基线血清肌酐水平通常是未知的。因此，肌酐水平升高可能会被误解为急性肾损伤，因为其部分原因可能是先前存在的 CKD。我们最近的研究结果强调了这个问题，表明虽然 17% 的住院 COVID-19 患者有 CKD 病史，但 93% 的患者表现出与该疾病一致的肾脏组织病理学特征 [2]。因此，对慢性病的诊断不足可能导致低估 ICU 患者合并症的真实负担和严重程度。因此，这些疾病对 HRQoL 的影响可能不准确地仅仅归因于 ICU 住院，而实际上，先前存在但未确诊的疾病发挥了重要作用。

此外，慢性健康问题的报告和管理也存在显着的性别差异。男性和女性可能会经历和报告合并症不同，也可能有不同的寻求健康行为[3]。例如，女性更有可能寻求医疗护理，因此她们的慢性病可能比男性更早得到诊断并得到更有效的治疗。这种差异可能会导致有关合并症的患病率及其对 HRQoL 的影响的数据出现偏差。

与 Orwelius 等人的观察类似，我们强调在 HRQoL 研究中使用年龄调整来解释合并症是不够的。近年来，诊断合并症的年龄发生了明显的变化，年轻人群越来越多地表现出传统上与老年人相关的慢性疾病。这种趋势很大程度上是由于现代社会普遍存在的不健康生活方式选择，例如不良的饮食习惯、缺乏运动和压力水平升高。因此，现在正在年轻人中诊断高血压、2 型糖尿病和肝病等疾病，这突出表明需要采用更细致的 HRQoL 研究方法。

有充分证据表明，重症监护病房后往往会导致慢性疾病，例如从急性肾损伤进展为慢性肾病 [4, 5]。越来越多的证据表明，其他慢性疾病，如糖尿病，也可能在 ICU 住院后出现 [6, 7]；然而，这种现象仍未得到充分研究。这一研究差距的部分原因是缺乏对慢性病及其严重程度在 ICU 入院和 ICU 后随访期间缺乏结构化和准确的诊断。新发慢性疾病或原有疾病恶化无疑会对 HRQoL 产生重大影响。因此，早期识别慢性病将带来更有效的管理策略，改善患者康复，最终提高 HRQoL，并减轻医疗保健系统的负担。

Orwelius 等人的综述强调了在未来研究中采用标准化、综合方法来评估合并症的必要性。所审查的研究中 HRQoL 测量工具和随访持续时间的异质性使得很难就合并症与 ICU 入住本身的真正影响得出明确的结论。例如，使用不同的工具，如 SF-36、EQ-5D 等，每个工具都有自己的优点和局限性，会导致报告的结果存在差异。此外，缺乏与未诊断和可能不受控制或早期合并症充分匹配的对照组，限制了分离 IC​​U 住院对 HRQoL 的具体影响的能力。此外，非 ICU 相关因素对 HRQoL 的影响通常被忽视，无论是否入住 ICU，都存在潜在的无法测量的混杂因素。测量 HRQoL 的标准化方法，加上可能需要实验室测试的彻底且一致的合并症评估，将增强未来研究的可比性和可靠性。

总之，解决合并症患病率数据的不准确性、考虑健康报告和管理中的性别差异以及采用标准化的 HRQoL 评估方法至关重要。此外，对血液和/或尿液样本进行实验室评估，以准确识别 ICU 入院时和 ICU 后随访期间的合并症至关重要。未来的研究必须纳入这些措施，以便更准确、更全面地了解 ICU 幸存者的合并症和影响 HRQoL 的其他因素。

 不适用。

 重症监护病房：

 重症监护病房

 人力资源生活质量：

健康相关的生活质量

 CKD：

 慢性肾脏病

 SF-36：

 简短形式 36 个问题

 EQ-5D：

 EuroQol 5 个维度

1. 
   Orwelius L、Wilhelms S、Sjöberg F。重症监护幸存者中健康相关生活质量的变化是否仅由合并症造成？针对特定目的的审查。危重护理。 2024 年；28:208。

   
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2. 
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3. 
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4. 
   参见 EJ、Jayasinghe K、Glassford N、Bailey M、Johnson DW、Polkinghorne KR 等人。急性肾损伤后不良后果的长期风险：使用暴露的共识定义对队列研究进行系统回顾和荟萃分析。肾脏国际。 2019；95：160–72。

   
   文章 PubMed 谷歌学术

5. 
   Fiorentino M、Grandaliano G、Gesualdo L、Castellano G。急性肾损伤到慢性肾病的转变。急性肾损伤基础研究临床实践。 2018；193：45–54。

   
   文章 CAS 谷歌学术

6. 
   Ali Abdelhamid Y、Kar P、Finnis ME、Phillips LK、Plummer MP、Shaw JE 等。危重患者的应激性高血糖和随后的糖尿病风险：系统评价和荟萃分析。危重护理。 2016；20：1–9。

    文章谷歌学术

7. 
   Jivanji CJ、Asrani VM、Windsor JA、Petrov MS。急性和危重疾病后新发糖尿病：系统评价。梅奥临床进程。 2017；92：762–73。

   
   文章 PubMed 谷歌学术

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1. 
   重症监护系，格罗宁根大学，格罗宁根大学医学中心，格罗宁根荷兰

   
   Jill Moser、Roos Mensink、Marisa Onrust、Fredrike Blokzijl 和 Jacqueline Koeze

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