Correlation of preoperative frailty with postoperative delirium and one-year mortality in Chinese geriatric patients undergoing noncardiac surgery: Study protocol for a prospective observational cohort study

Min Zhang; Xiaojun Gao; Mengjie Liu; Zhongquan Gao; Xiaxuan Sun; Linlin Huang; Ting Zou; Yongle Guo; Lina Chen; Yang Liu; Xiaoning Zhang; Hai Feng; Yuelan Wang; Yongtao Sun

doi:10.1371/journal.pone.0295500

. 2024 Mar 6;19(3):e0295500. doi: 10.1371/journal.pone.0295500

Correlation of preoperative frailty with postoperative delirium and one-year mortality in Chinese geriatric patients undergoing noncardiac surgery: Study protocol for a prospective observational cohort study

Min Zhang ^1,^#, Xiaojun Gao ^1,^#, Mengjie Liu ¹, Zhongquan Gao ^1,², Xiaxuan Sun ^1,², Linlin Huang ³, Ting Zou ³, Yongle Guo ^1,², Lina Chen ¹, Yang Liu ¹, Xiaoning Zhang ¹, Hai Feng ¹, Yuelan Wang ⁴, Yongtao Sun ^1,^*

Editor: Silvia Fiorelli⁵

¹Department of Anesthesiology, Shandong Institute of Anesthesia and Respiratory Critical Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China

²Department of Anesthesiology, Shandong First Medical University, Jinan, China

³Department of Nursing, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China

⁴Department of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University (Shandong Provincial Hospital), Jinan, China

⁵Sapienza University of Rome: Universita degli Studi di Roma La Sapienza, ITALY

Competing Interests: The authors have declared that no competing interests exist.

^✉

* E-mail: ytsun@sdfmu.edu.cn

Contributed equally.

Roles

Min Zhang: Conceptualization, Data curation, Investigation, Resources

Xiaojun Gao: Data curation, Investigation, Methodology, Project administration, Writing – original draft

Mengjie Liu: Data curation, Investigation, Project administration, Resources, Software, Visualization

Zhongquan Gao: Data curation, Investigation, Methodology, Resources, Software, Validation

Xiaxuan Sun: Data curation, Investigation, Methodology, Resources, Validation

Linlin Huang: Data curation, Investigation, Methodology, Resources, Validation

Ting Zou: Data curation, Formal analysis, Investigation, Supervision

Yongle Guo: Data curation, Investigation, Resources, Validation, Visualization

Lina Chen: Data curation, Investigation, Software, Writing – review & editing

Yang Liu: Data curation, Investigation, Project administration, Software, Validation, Writing – original draft

Xiaoning Zhang: Data curation, Investigation, Resources, Supervision

Hai Feng: Conceptualization, Data curation, Methodology, Validation

Yuelan Wang: Conceptualization, Data curation, Investigation, Methodology, Validation

Yongtao Sun: Conceptualization, Data curation, Funding acquisition, Investigation, Methodology, Writing – original draft, Writing – review & editing

Silvia Fiorelli: Editor

PMCID: PMC10917300 PMID: 38446754

Abstract

Background

To Frailty is associated with postoperative delirium (POD) but is rarely assessed in patients undergoing noncardiac surgery. In this study, the correlation between preoperative frailty and POD, one-year mortality will be investigated in noncardiac Chinese geriatric surgery patients.

Methods

This study is a prospective, observational, cohort study conducted at a single center with Chinese geriatric patients. Patients who undergo noncardiac surgery and are older than 70 years will be included. A total of 536 noncardiac surgery patients will be recruited from the First Affiliated Hospital of Shandong First Medical University for this study. The Barthel Index (BI) rating will be used to assess the patient’s ability to carry out everyday activities on the 1st preoperative day. The modified frailty index (mFI) will be used to assess frailty. Patients in the nonfrailty group will have an mFI < 0.21, and patients in the frailty group will have an mFI ≥ 0.21. The primary outcome is the incidence of POD. Three-Minute Diagnostic Interview for CAM-defined Delirium (3D-CAM) will be conducted twice daily during the 1st-7th postoperative days, or just before discharge. The secondary outcomes will include one-year mortality, in-hospital cardiopulmonary events, infections, acute renal injury, and cerebrovascular events.

Discussion

This study will clarify the correlation of preoperative frailty with POD and one-year all-cause mortality in Chinese geriatric patients undergoing noncardiac surgery. Can preoperative frailty predict POD or one-year mortality? In the face of China’s serious aging social problems, this result may have important clinical value for the surgical treatment of geriatric patients.

Trial registration

This protocol has been registered with ClinicalTrials. Gov on 12 January 2022 (https://clinicaltrials.gov/ct2/show/NCT05189678).

Background

Geriatric adults often suffer from delirium, an acute disorder of attention and cognition, which can be life-threatening. Following an acute illness, surgery, or hospitalization [1], delirium often sets off a series of events that lead to institutionalization, loss of independence, increased morbidity and mortality, and high healthcare expenditure costs [2]. POD is a difficult and complex illness that typically develops 24 to 72 hours after surgery and affects 20% to 80% of geriatric individual patients [3,4]. Aging-related problems are getting worse. More significantly, geriatric patients have undergone surgery frequently over the previous 20 years. Compared to aging, more people are getting sick [5]. In addition, studies have shown that frailty is also more prevalent in the surgical group (frailty percentage 42%–50%) than in the nonsurgical aged population (frailty proportion 4%–10%) [6–8]. Therefore, it is imperative to preoperatively assess the overall health status of geriatric patients and to quickly reverse or lessen their frailty [9].

One of the biggest threats to world health in the twenty-first century is frailty, which goes beyond chronological age. The clinical syndrome of frailty is defined as “a loss of physiological capabilities and reserves in several organ systems that is accompanied by an increased sensitivity to stressors.” [10–12]. In spite of the fact that geriatric patients are equally likely to have positive postoperative outcomes as younger patients, fragile patients are more likely to have negative outcomes [13,14]. Postoperative complications can be predicted by preoperative frailty [15,16], including delirium [17,18], falls [19,20], prolonged hospitalizations [21], hospital readmissions [21], discharge to a nursing or assisted-living facility [22], and other surgical complications [16,23]. Elderly frailty is also associated with lower quality of life [8] as well as an accurate predictor of all-cause mortality [16,24,25].

Age, operation type, intensive care unit (ICU) admission, pain, and some drugs are just a few of the many recognized changeable and nonmodifiable risk factors for POD. One of the major risk factors that cannot be changed is age. Accordingly, preoperative screening for geriatric illnesses that are linked to POD and predict poor surgical outcomes is advised for patients undergoing geriatric surgery [26]. The most critical factor is frailty, which is a strong predictor of a range of poor health outcomes in the aged, including falls, disability, and dementia [10,27]. Frailty has been shown to be the most prevalent disease that results in death in geriatric patients [28], which stresses the significance of recognizing frailty in geriatric patients in clinical practice. Frailty is also an independent predictor of postoperative outcome [29]. The therapeutic value of preoperative decision-making and prognostic assessment depends on the early detection of fragile patients. Preoperative frailty has not yet been proven to be a separate risk factor for POD [30]. This study will look at the relationship between preoperative fragility and the prevalence of POD and one-year mortality undergoing noncardiac surgery.

Methods/Design

The protocol was written in accordance with the Standard Protocol Items: Recommendations for Interventional Trials guidelines [31]; the protocol is summarised in Figs 1 and 2.

Fig 1 — MMSE, Mini-mental State Examination; BI, Barthel Indexl; mFI, modified frailty index; aCCI, age-adjusted Charlson Comorbidity Index; 3D-CAM, 3-Minute Diagnostic Confusion Assessment Method; CAM-ICU, confusion assessment model for intensive care unit.

This is a single-centre, prospective, observational, cohort study of preoperative frailty and POD in geriatric patients undergoing noncardiac surgery. Therefore, the study was designed without intervention, randomization and blindness.

Participants

Patients with an ASA grade I–IV, age ≥ 70 years, and undergoing noncardiac surgery will be chosen from February 2022 to December 2023. The preoperative assessment will make use of the mFI and MMSE. Patients in the nonfrailty group will have a mFI < 0.21, and those in the frailty group will have a mFI ≥ 0.21. Enrollment will end once the projected sample size of patients in both groups has been reached.

Sample size calculation

The main outcome will be the incidence of POD. Based on literature review and early study results, the estimated incidence of frailty in surgical patients was 23.0%, while the incidence of POD in the frailty and nonfrailty groups was 35.7% and21.7%. PASS 15.0 software was used to determine the sample size for the independent sample rate comparison of the two groups. The ratio of samples between the experimental and control groups was 0.303, and the two-sided test. Test level (α), and inspection effectiveness (1-β) were set at 0.05 and 0.80, respectively. This calculation yielded a sample size of 112 patients in the frailty group and 370 patients in the nonfrailty group. Considering 10% dropout rate, a total of 536 study volunteers will be required, consisting of 411 patients in the nonfailty group and 125 patients in the failty group.

Eligibility criteria

Inclusion and exclusion criteria are listed in Table 1.

Table 1. Inclusion and exclusion criteria.

Eligibility criteria

Inclusion criteria

Age ≥ 70 years;
ASA I—IV level;
Patients with a signed the informed consent form for the clinical study;
Patients scheduled to undergo noncardiac surgery.

Exclusion criteria

Refuse to participate;
Hospital stay <3 days;
Emergency surgery;
Patients can only be included once, regardless of whether the cause of the second operation is related to the first cause;
Speech impairment or severe hearing or vision impairment that prevents communication;
Central nervous system diseases (dementia, depression);
Severe renal insufficiency (requiring dialysis);
Severe abnormal liver function (Child-Pugh score ≥ 10);
Participation in other relevant clinical studies within 3 months;
MMSE examination confirmed the existence of cognitive dysfunction: illiteracy ≤ 17 points, primary school level ≤ 20 points, secondary school level (including technical secondary school) ≤ 22 points, university level (including junior college) ≤ 23 points.

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Shedding criteria

Study participants who refuse to provide informed consent or withdraw from the study.

Study implementation

All members of the research team will receive systematic training to master and use the MMSE, aCCI, mFI, BI, 3D-CAM, and CAM-ICU before the study and may only participate after passing the examination.

Preoperative frailty assessment: The mFI is a National Surgical Quality Improvement Gauge (NSQIP)-based 11-factor index that has been proven to adequately reflect frailty and predict mortality and morbidity [32]. The mFI is calculated by dividing the number of factors present for a patient by the number of available factors for which there are no missing data [33]. An mFI score of 0 is classified as healthy, 0–0.21 is classified as a prefrail, and ≥ 0.21 is classified as a prefrail. The index includes 11 items: nonindependent function or activity status; history of diabetes; history of chronic obstructive pulmonary disease (COPD) or pneumonia; history of congestive heart failure; history of myocardial infarction; angina pectoris, percutaneous coronary intervention (PCI), cardiac surgery; hypertension requiring medication; peripheral vascular disease or static pain; sensory disturbance; transient ischaemic attack (TIA) attack or cerebrovascular accident without sequelae; cerebrovascular accident with sequelae [34]. In this study, patients with moderate and severe dysfunction with a BI ≤ 60 are considered to be positive for item 1. The advantage is that it has been employed and is frequently used in the risk classification of various surgical operations in the NSQIP database of the United States.The majority of evaluation indexes are comorbidities, poor nutrition, metabolism, and other physical function indexes, which is a drawback.
Assessment of activities of daily living: The patients will be assessed preoperatively by the BI evaluation form; 0–40 is classified as severe dysfunction, 41–60 is classified as moderate dysfunction, 61–99 is classified as mild dysfunction, and 100 is classified as self-care.
Diagnosis of POD: The 3D-CAM will be used to evaluate POD twice a day (8:00–10:00 and 18:00–20:00) on the the 1^st to 7^th postoperative days. The 3D-CAM provides a brief assessment (3 orientation items, 4 attention items, 3 symptom probes, and 10 observational items) that facilitates rating of the 4 core CAM features and has a sensitivity of 95% and specificity of 94% when compared with a clinical reference standard rating in a prospective validation study in hospitalized patients [35].

Primary outcome

The primary outcome will be the incidence of POD.

Secondary outcomes

The incidence of 30-day readmission, one-year all-cause mortality, postoperative complications (such as pulmonary infection, urinary tract infection, cardiovascular and cerebrovascular accidents, abnormal liver function, postoperative bleeding, incision infection, lower extremity deep venous thrombosis, electrolyte disorder, and hypoproteinemia), and postoperative complications (such as infection of the incision, infection of the incision site, and postoperative bleeding) will all be considered secondary outcomes. According to the attending physicians’ definition, a hospital stay is the period of time between admission and discharge.

Participant timeline

On the day before surgery, candidates will be scrutinized according to the inclusion and exclusion criteria. According to their mFI scores, researchers will classify the participants into the frailty group or the nonfrailty group after receiving written informed consent. We’ll keep track of every intraoperative variable.

From the first to the third postoperative day, the patients will be checked on once in the morning and once in the afternoon, and the 3D-CAM score will be taken to gauge the frequency and seriousness of delirium. On the 30^th postoperative day, a phone follow-up will be finished, and any issues that develop within 30 days of the procedure will be noted.

Recruitment

In the day before surgery, we will recruit the patients and explain the study protocol to them. Before deciding whether to participate, the patient will receive enough time to read and assess the information and ask questions. If the patient refuses to participate, the quality of the perioperative management will not be adversely affected.

Data collection methods

Researchers who are responsible for data management will collect participant data. The data collection files will be standardized to ensure that all data are recorded and can be analyzed in the future. It will be necessary to have at least two researchers (an operator and a research assistant) collect data in each case, and the research assistant will be responsible for supplementing and improving the Case Report Form (CRF) form.

Data management

According to the findings of the initial observation, researchers will promptly, completely, and accurately enter data on the CRF. According to the plan, the research coordinator will ensure that the study is conducted. The CRF will be delivered to the researchers in charge of data management after being completed and approved by the project’s general director. One researcher will enter the data, and a second researcher will review it. CRF will be kept in order. The data management is always subject to review by the ethical committee.

Patient and public participation

In the creation of research questions, study design, intervention designs, outcome measurements, recruiting, or study execution, patients are not directly involved. The patients will be notified by phone or message of any conference presentations and publications at the conclusion of this study.

Statistical methods

Continuous variables will be subjected to normality tests (such as age). If the data have a normal distribution, the mean ± standard deviation will be used to represent the data. Intergroup comparisons will be made using independent-sample t tests. In the absence of a normal distribution, medians (interquartile range) will be used to express the data, and the Wilcoxon rank sum test will be applied to compare the groups. A categorical variable, such as the sex or complications, will be expressed as a frequency (percentage). We will use either the chi-square test or Fisher’s exact probability approach for intergroup comparisons.

The primary outcomes of POD will be analyzed using a logistic regression model. The correlation between weakness and POD will be calculated using odds ratios (ORs) and 95% confidence intervals (CIs).

Kaplan-Meier survival curves will be used to describe the incidence of secondary outcomes. We will use the log-rank test to compare the differences between groups. A Cox regression model will be used to analyze the influencing factors for 30-day readmissions and complications.

In order to compare the abscission rate between the two groups, the chi-square test will be used.

All statistical analyses will be conducted using the two-sided test with a p value < 0.05 considered statistically significant.

Ethics approval and consent to participate

Our research is conducted in accordance with the principles of the Declaration of Helsinki (64th WMA General Assembly, October 2013) and was approved by the Ethics Committee of First Affiliated Hospital of Shandong First Medical University. Written informed consent will be obtained from all participants and/or their legal representatives. The results will be disseminated through a peer-reviewed publication and in conferences or congresses.

Discussion

Older adults with frailty are becoming more prevalent as a result of the rapidly aging population [36,37], which in turn puts more strain on the world’s healthcare systems [38]. Older adults with frailty are more likely to experience unmet care needs, fractures and falls, hospitalizations, iatrogenic consequences, and early mortality [14,39–43]. Surgical patients who are geriatric are more likely to experience "age-related events," mainly respiratory complications (pneumonia and respiratory failure), heart problems, postoperative cognitive impairment, an increased likelihood of ICU admission, an extended hospital stay, and higher mortality [44].

Consequently, strategies that target the prevention and management of frailty in an ageing population will probably reduce the burden that the condition imposes on both the individual and health systems. It is recognized that frailty is a clinical syndrome related to aging [45–47] that it is often characterized by a decline in many organ systems’ physiological capacity [14,42,47,48], making them more susceptible to stress [14,42,43,45–47]. The functional capacity of a fragile person rapidly diminishes when stressor events occur (such as an acute illness). In order to prevent or reduce frailty from progressing into significant functional impairments, health care policy and supply must implement interventions to prevent or reduce frailty. One of the most typical clinical consequences in geriatric patients is POD [2,3,18]. Its incidence is also directly tied to a number of severe postoperative complications, and the two together are linked to extremely detrimental outcomes. In order to improve perioperative management through early preoperative identification of frail patients, an examination of the impact of preoperative frailty on delirium in geriatric patients undergoing noncardiac surgery is the purpose of this study. This will help prevent or reduce the occurrence of POD and a number of serious consequences.

According to the inclusion and exclusion criteria, patients will undergo a rigorous screening process. Researchers who have been trained and evaluated will do the preoperative and postoperative follow-up and data collecting for the chosen patients. This research is based on observation. The conclusions will reflect the significance of preoperative frailty assessment and further demonstrate which frailty index indicators are independent risk factors related to POD from the findings of multivariate regression analysis. In geriatric patients undergoing noncardiac surgery, this will serve as a basis for preventing POD.

Trial status

This is the fourth version of the protocol. The first pre-screened participant was invited to be informed about the study on February 7th, 2022. The recruitment phase or the data collection phase of the trial will be completed by the end of December 2023 including post-test and one-year mortality measurements.

Supporting information

S1 File. Study protocol English.

(DOC)

pone.0295500.s001.doc^{(61.2KB, doc)}

S2 File. Study protocol Chinese.

(DOC)

pone.0295500.s002.doc^{(72KB, doc)}

Abbreviations

3D-CAM: 3-Minute Diagnostic Interview for CAM-defined Delirium
aCCI: age-adjusted Charlson Comorbidity Index
BI: Barthel Index
CAM-ICU: confusion assessment model for intensive care unit
CIs: confidence intervals
COPD: chronic obstructive pulmonary disease
CRF: Case Report Form
ICU: intensive care unit
mFI: modified frailty index
MMSE: Mini-Mental State Exam
ORs: odds ratios
PCI: percutaneous coronary intervention
POD: postoperative delirium
TIA: transient ischaemic attack

Data Availability

No datasets were generated or analysed during the current study. All relevant data from this study will be made available upon study completion.

Funding Statement

1. Project 2019QL015 supported by the Academic Promotion Programme of Shandong First Medical University. YW, YS, ML, Shandong First Medical University, financial support 20 million RMB, https://www.sdfmu.edu.cn/ . 2. Project 202019170 supported by the Jinan Science and Technology Plan (Clinical Medicine Science and Technology Innovation Plan). YS, MZ, QG, JG, Jinan Science and Technology Bureau, financial support 100 thousand RMB, http://jnsti.jinan.gov.cn/ . 3. Project ZR2022MH221 supported by the Shandong Provincial Natural Science Foundation. YS, MZ, ML, XG, ZG, YG, Natural Science Foundation of Shandong Province, financial support 100 thousand RMB, http://cloud.kjt.shandong.gov.cn/ . The funders had and will not have a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

References

1.Chou MY, Wang YC, Peng LN, Liang CK, Chu CS, Liao MC, et al. Intraoperative blood transfusion predicts postoperative delirium among older patients undergoing elective orthopedic surgery: A prospective cohort study. Int J Geriatr Psychiatry. 2019;34(6):881–8. Epub 2019/02/15. doi: 10.1002/gps.5086 . [DOI] [PubMed] [Google Scholar]
2.Oh ES, Fong TG, Hshieh TT, Inouye SK. Delirium in Older Persons: Advances in Diagnosis and Treatment. Jama. 2017;318(12):1161–74. Epub 2017/10/04. doi: 10.1001/jama.2017.12067 . [DOI] [PMC free article] [PubMed] [Google Scholar]
3.Inouye SK, Westendorp RG, Saczynski JS. Delirium in elderly people. Lancet. 2014;383(9920):911–22. Epub 2013/09/03. doi: 10.1016/S0140-6736(13)60688-1 . [DOI] [PMC free article] [PubMed] [Google Scholar]
4.Inouye SK. Delirium in older persons. N Engl J Med. 2006;354(11):1157–65. Epub 2006/03/17. doi: 10.1056/NEJMra052321 . [DOI] [PubMed] [Google Scholar]
5.Etzioni DA, Liu JH, Maggard MA, Ko CY. The aging population and its impact on the surgery workforce. Ann Surg. 2003;238(2):170–7. Epub 2003/08/02. doi: 10.1097/01.SLA.0000081085.98792.3d . [DOI] [PMC free article] [PubMed] [Google Scholar]
6.Kojima G, Iliffe S, Jivraj S, Walters K. Association between frailty and quality of life among community-dwelling older people: a systematic review and meta-analysis. J Epidemiol Community Health. 2016;70(7):716–21. Epub 2016/01/20. doi: 10.1136/jech-2015-206717 . [DOI] [PubMed] [Google Scholar]
7.Parmar KL, Law J, Carter B, Hewitt J, Boyle JM, Casey P, et al. Frailty in Older Patients Undergoing Emergency Laparotomy: Results From the UK Observational Emergency Laparotomy and Frailty (ELF) Study. Ann Surg. 2021;273(4):709–18. Epub 2019/06/13. doi: 10.1097/SLA.0000000000003402 . [DOI] [PubMed] [Google Scholar]
8.Gómez Jiménez E, Avendaño Céspedes A, Cortés Zamora EB, García Molina R, Abizanda P. [Frailty prevalence in hospitalized older adults. A systematic review.]. Rev Esp Salud Publica. 2021;95. Epub 2021/10/09. . [PubMed] [Google Scholar]
9.Penning Y, El Asmar A, Moreau M, Raspé J, Dal Lago L, Pepersack T, et al. Evaluation of the Comprehensive Geriatric Assessment (CGA) tool as a predictor of postoperative complications following major oncological abdominal surgery in geriatric patients. PLoS One. 2022;17(3):e0264790. Epub 2022/03/04. doi: 10.1371/journal.pone.0264790 . [DOI] [PMC free article] [PubMed] [Google Scholar]
10.Dent E, Martin FC, Bergman H, Woo J, Romero-Ortuno R, Walston JD. Management of frailty: opportunities, challenges, and future directions. Lancet. 2019;394(10206):1376–86. Epub 2019/10/15. doi: 10.1016/S0140-6736(19)31785-4 . [DOI] [PubMed] [Google Scholar]
11.Fried LP, Ferrucci L, Darer J, Williamson JD, Anderson G. Untangling the concepts of disability, frailty, and comorbidity: implications for improved targeting and care. J Gerontol A Biol Sci Med Sci. 2004;59(3):255–63. Epub 2004/03/20. doi: 10.1093/gerona/59.3.m255 . [DOI] [PubMed] [Google Scholar]
12.Robinson TN, Walston JD, Brummel NE, Deiner S, Brown CHt, Kennedy M, et al. Frailty for Surgeons: Review of a National Institute on Aging Conference on Frailty for Specialists. J Am Coll Surg. 2015;221(6):1083–92. Epub 2015/10/01. doi: 10.1016/j.jamcollsurg.2015.08.428 . [DOI] [PMC free article] [PubMed] [Google Scholar]
13.Huisman MG, Kok M, de Bock GH, van Leeuwen BL. Delivering tailored surgery to older cancer patients: Preoperative geriatric assessment domains and screening tools—A systematic review of systematic reviews. Eur J Surg Oncol. 2017;43(1):1–14. Epub 2016/07/14. doi: 10.1016/j.ejso.2016.06.003 . [DOI] [PubMed] [Google Scholar]
14.Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet. 2013;381(9868):752–62. Epub 2013/02/12. doi: 10.1016/S0140-6736(12)62167-9 . [DOI] [PMC free article] [PubMed] [Google Scholar]
15.Dasgupta M, Rolfson DB, Stolee P, Borrie MJ, Speechley M. Frailty is associated with postoperative complications in older adults with medical problems. Arch Gerontol Geriatr. 2009;48(1):78–83. Epub 2007/12/11. doi: 10.1016/j.archger.2007.10.007 . [DOI] [PubMed] [Google Scholar]
16.Lin HS, Watts JN, Peel NM, Hubbard RE. Frailty and post-operative outcomes in older surgical patients: a systematic review. BMC Geriatr. 2016;16(1):157. Epub 2016/09/02. doi: 10.1186/s12877-016-0329-8 . [DOI] [PMC free article] [PubMed] [Google Scholar]
17.Susano MJ, Grasfield RH, Friese M, Rosner B, Crosby G, Bader AM, et al. Brief Preoperative Screening for Frailty and Cognitive Impairment Predicts Delirium after Spine Surgery. Anesthesiology. 2020;133(6):1184–91. Epub 2020/09/09. doi: 10.1097/ALN.0000000000003523 . [DOI] [PMC free article] [PubMed] [Google Scholar]
18.Gracie TJ, Caufield-Noll C, Wang NY, Sieber FE. The Association of Preoperative Frailty and Postoperative Delirium: A Meta-analysis. Anesth Analg. 2021;133(2):314–23. Epub 2021/07/15. doi: 10.1213/ANE.0000000000005609 . [DOI] [PMC free article] [PubMed] [Google Scholar]
19.Schultz M, Rosted E, Sanders S. Frailty is associated with a history with more falls in elderly hospitalised patients. Dan Med J. 2015;62(6). Epub 2015/06/04. . [PubMed] [Google Scholar]
20.Kojima G. Frailty as a Predictor of Future Falls Among Community-Dwelling Older People: A Systematic Review and Meta-Analysis. J Am Med Dir Assoc. 2015;16(12):1027–33. Epub 2015/08/10. doi: 10.1016/j.jamda.2015.06.018 . [DOI] [PubMed] [Google Scholar]
21.Boyd CM, Xue QL, Simpson CF, Guralnik JM, Fried LP. Frailty, hospitalization, and progression of disability in a cohort of disabled older women. Am J Med. 2005;118(11):1225–31. Epub 2005/11/08. doi: 10.1016/j.amjmed.2005.01.062 . [DOI] [PubMed] [Google Scholar]
22.Makary MA, Segev DL, Pronovost PJ, Syin D, Bandeen-Roche K, Patel P, et al. Frailty as a predictor of surgical outcomes in older patients. J Am Coll Surg. 2010;210(6):901–8. Epub 2010/06/01. doi: 10.1016/j.jamcollsurg.2010.01.028 . [DOI] [PubMed] [Google Scholar]
23.McIsaac DI, Bryson GL, van Walraven C. Association of Frailty and 1-Year Postoperative Mortality Following Major Elective Noncardiac Surgery: A Population-Based Cohort Study. JAMA Surg. 2016;151(6):538–45. Epub 2016/01/23. doi: 10.1001/jamasurg.2015.5085 . [DOI] [PubMed] [Google Scholar]
24.Kulmala J, Nykänen I, Hartikainen S. Frailty as a predictor of all-cause mortality in older men and women. Geriatr Gerontol Int. 2014;14(4):899–905. Epub 2014/03/29. doi: 10.1111/ggi.12190 . [DOI] [PubMed] [Google Scholar]
25.Lee DH, Buth KJ, Martin BJ, Yip AM, Hirsch GM. Frail patients are at increased risk for mortality and prolonged institutional care after cardiac surgery. Circulation. 2010;121(8):973–8. Epub 2010/02/18. doi: 10.1161/CIRCULATIONAHA.108.841437 . [DOI] [PubMed] [Google Scholar]
26.Chow WB, Rosenthal RA, Merkow RP, Ko CY, Esnaola NF. Optimal preoperative assessment of the geriatric surgical patient: a best practices guideline from the American College of Surgeons National Surgical Quality Improvement Program and the American Geriatrics Society. J Am Coll Surg. 2012;215(4):453–66. Epub 2012/08/25. doi: 10.1016/j.jamcollsurg.2012.06.017 . [DOI] [PubMed] [Google Scholar]
27.Aldecoa C, Bettelli G, Bilotta F, Sanders RD, Audisio R, Borozdina A, et al. European Society of Anaesthesiology evidence-based and consensus-based guideline on postoperative delirium. Eur J Anaesthesiol. 2017;34(4):192–214. Epub 2017/02/12. doi: 10.1097/EJA.0000000000000594 . [DOI] [PubMed] [Google Scholar]
28.Gill TM, Gahbauer EA, Han L, Allore HG. Trajectories of disability in the last year of life. N Engl J Med. 2010;362(13):1173–80. Epub 2010/04/02. doi: 10.1056/NEJMoa0909087 . [DOI] [PMC free article] [PubMed] [Google Scholar]
29.Amini S, Crowley S, Hizel L, Arias F, Libon DJ, Tighe P, et al. Feasibility and Rationale for Incorporating Frailty and Cognitive Screening Protocols in a Preoperative Anesthesia Clinic. Anesth Analg. 2019;129(3):830–8. Epub 2019/08/20. doi: 10.1213/ANE.0000000000004190 . [DOI] [PMC free article] [PubMed] [Google Scholar]
30.Mou Q, Gao M, Liu X, Wei C, Lan G, Zhao X, et al. Preoperative anxiety as an independent predictor of postoperative delirium in older patients undergoing elective surgery for lumbar disc herniation. Aging Clin Exp Res. 2023;35(1):85–90. Epub 2022/10/20. doi: 10.1007/s40520-022-02278-7 . [DOI] [PubMed] [Google Scholar]
31.Chan AW, Tetzlaff JM, Altman DG, Laupacis A, Gøtzsche PC, Krle AJK, et al. SPIRIT 2013 Statement: defining standard protocol items for clinical trials. Rev Panam Salud Publica. 2015;38(6):506–14. Epub 2016/07/22. . [PMC free article] [PubMed] [Google Scholar]
32.Velanovich V, Antoine H, Swartz A, Peters D, Rubinfeld I. Accumulating deficits model of frailty and postoperative mortality and morbidity: its application to a national database. J Surg Res. 2013;183(1):104–10. Epub 2013/02/19. doi: 10.1016/j.jss.2013.01.021 . [DOI] [PubMed] [Google Scholar]
33.Subramaniam S, Aalberg JJ, Soriano RP, Divino CM. New 5-Factor Modified Frailty Index Using American College of Surgeons NSQIP Data. J Am Coll Surg. 2018;226(2):173–81.e8. Epub 2017/11/21. doi: 10.1016/j.jamcollsurg.2017.11.005 . [DOI] [PubMed] [Google Scholar]
34.Katiyar V, Sharma R, Tandon V, Goda R, Ganeshkumar A, Suri A, et al. Impact of frailty on surgery for glioblastoma: a critical evaluation of patient outcomes and caregivers’ perceptions in a developing country. Neurosurg Focus. 2020;49(4):E14. Epub 2020/10/02. doi: 10.3171/2020.7.FOCUS20482 . [DOI] [PubMed] [Google Scholar]
35.Marcantonio ER, Ngo LH, O’Connor M, Jones RN, Crane PK, Metzger ED, et al. 3D-CAM: derivation and validation of a 3-minute diagnostic interview for CAM-defined delirium: a cross-sectional diagnostic test study. Ann Intern Med. 2014;161(8):554–61. doi: 10.7326/M14-0865 . [DOI] [PMC free article] [PubMed] [Google Scholar]
36.Yu R, Wong M, Chong KC, Chang B, Lum CM, Auyeung TW, et al. Trajectories of frailty among Chinese older people in Hong Kong between 2001 and 2012: an age-period-cohort analysis. Age Ageing. 2018;47(2):254–61. doi: 10.1093/ageing/afx170 . [DOI] [PubMed] [Google Scholar]
37.Mousa A, Savva GM, Mitnitski A, Rockwood K, Jagger C, Brayne C, et al. Is frailty a stable predictor of mortality across time? Evidence from the Cognitive Function and Ageing Studies. Age Ageing. 2018;47(5):721–7. doi: 10.1093/ageing/afy077 . [DOI] [PMC free article] [PubMed] [Google Scholar]
38.Ilinca S, Calciolari S. The patterns of health care utilization by elderly Europeans: frailty and its implications for health systems. Health Serv Res. 2015;50(1):305–20. Epub 20140819. doi: 10.1111/1475-6773.12211 . [DOI] [PMC free article] [PubMed] [Google Scholar]
39.Hoogendijk EO, Muntinga ME, van Leeuwen KM, van der Horst HE, Deeg DJ, Frijters DH, et al. Self-perceived met and unmet care needs of frail older adults in primary care. Arch Gerontol Geriatr. 2014;58(1):37–42. Epub 20130912. doi: 10.1016/j.archger.2013.09.001 . [DOI] [PubMed] [Google Scholar]
40.Vermeiren S, Vella-Azzopardi R, Beckwée D, Habbig AK, Scafoglieri A, Jansen B, et al. Frailty and the Prediction of Negative Health Outcomes: A Meta-Analysis. J Am Med Dir Assoc. 2016;17(12):1163.e1-.e17. doi: 10.1016/j.jamda.2016.09.010 . [DOI] [PubMed] [Google Scholar]
41.Yang X, Lupón J, Vidán MT, Ferguson C, Gastelurrutia P, Newton PJ, et al. Impact of Frailty on Mortality and Hospitalization in Chronic Heart Failure: A Systematic Review and Meta-Analysis. J Am Heart Assoc. 2018;7(23):e008251. doi: 10.1161/JAHA.117.008251 . [DOI] [PMC free article] [PubMed] [Google Scholar]
42.Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56(3):M146–56. Epub 2001/03/17. doi: 10.1093/gerona/56.3.m146 . [DOI] [PubMed] [Google Scholar]
43.Junius-Walker U, Onder G, Soleymani D, Wiese B, Albaina O, Bernabei R, et al. The essence of frailty: A systematic review and qualitative synthesis on frailty concepts and definitions. Eur J Intern Med. 2018;56:3–10. Epub 20180531. doi: 10.1016/j.ejim.2018.04.023 . [DOI] [PubMed] [Google Scholar]
44.Tanaka S, Ueno M, Iida H, Kaibori M, Nomi T, Hirokawa F, et al. Preoperative assessment of frailty predicts age-related events after hepatic resection: a prospective multicenter study. J Hepatobiliary Pancreat Sci. 2018;25(8):377–87. Epub 20180723. doi: 10.1002/jhbp.568 . [DOI] [PubMed] [Google Scholar]
45.Morley JE, Vellas B, van Kan GA, Anker SD, Bauer JM, Bernabei R, et al. Frailty consensus: a call to action. J Am Med Dir Assoc. 2013;14(6):392–7. doi: 10.1016/j.jamda.2013.03.022 . [DOI] [PMC free article] [PubMed] [Google Scholar]
46.Rockwood K, Mitnitski A. Frailty defined by deficit accumulation and geriatric medicine defined by frailty. Clin Geriatr Med. 2011;27(1):17–26. doi: 10.1016/j.cger.2010.08.008 . [DOI] [PubMed] [Google Scholar]
47.Xue QL. The frailty syndrome: definition and natural history. Clin Geriatr Med. 2011;27(1):1–15. doi: 10.1016/j.cger.2010.08.009 . [DOI] [PMC free article] [PubMed] [Google Scholar]
48.Dent E, Kowal P, Hoogendijk EO. Frailty measurement in research and clinical practice: A review. Eur J Intern Med. 2016;31:3–10. Epub 20160331. doi: 10.1016/j.ejim.2016.03.007 . [DOI] [PubMed] [Google Scholar]

PLoS One. doi: 10.1371/journal.pone.0295500.r001

Decision Letter 0

Walid Kamal Abdelbasset

3 Feb 2023

PONE-D-22-32948Correlation of preoperative frailty with postoperative delirium and one-year mortality in Chinese geriatric undergoing noncardiac surgery patients: study protocol for a prospective observational cohort studyPLOS ONE

Dear Dr. Sun,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

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PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors report a study protocol for assessing the association between preoperative frailty and postoperative delirium and one-year mortality in Chinese patients after noncardiac surgery. Detailed information is reported according to guidelines and SPIRIT checklist has been attached.

It would be better if the authors could clarify following questions:

1. Please clarify the reason why the authors registered patients aged ≥ 70 years, not ≥ 60 or 65 years? In general, the elderly refers to people over the age of 65.

2. Please clarify the participant registration was randomized or not.

3. Please clarify the reason why your study population excluded patients who scheduled to undergo cardiac surgery. Is it due to the modified frailty index includes cardiac surgery? Please further clarify the impact of doing so. This experimental design could affect the generalization of the conclusions. How do you explain that?

4. The modified frailty index was used as diagnostic tools of frailty according to study protocol. Please add related references, and clarify the reason why you used that rather than other criteria such as the Fried's criteria and described the advantages and limitations of that index.

5. The authors stated that “In addition, studies have shown that frailty is also more prevalent in the surgical group (frailty percentage 42%–50%) than in the nonsurgical aged population (frailty proportion 4%–10%) [5-7].” in the introduction, but “Based on literature review and early study results, the estimated incidence of frailty was 23%” in sample size calculation.

The estimated incidence of frailty in your study is more than twice that of non-surgical group in previous studies (and about one-half that of the surgical group). Please clarify the reason why the incidence (23%) was higher than previous studies and possible impact of the high incidence.

Reviewer #2: This is a study protocol to investigate the Correlation of preoperative frailty with postoperative delirium and one-year mortality in

Chinese geriatric undergoing noncardiac surgery patients: study protocol for a

prospective observational cohort study.

At first the title has to be rearranged to :

Correlation of preoperative frailty with postoperative delirium and one-year mortality in Chinese geriatric patients undergoing noncardiac surgery: study protocol for a prospective observational cohort study.

In the abstract: rearrange the sentence: Frailty is associated with postoperative delirium (POD) but is rarely assessed undergoing noncardiac surgery patients

To Frailty is associated with postoperative delirium (POD) but is rarely assessed in patients undergoing noncardiac surgery.

In the Abstract methods: (The study will be carried out in an operating room at a university hospital). This seems strange!

In the Background: (More people are becoming patients than are getting older. )This is grammatically incorrect.

Also, (the connection between preoperative frailty and the prevalence of POD, one-year mortality undergoing noncardiac surgery will be examined in this study), needs correction.

In general, a reasonable study protocol

Reviewer #3: Dear the author of the manuscript. Entitled. Correlation of preoperative reality. With post operative delirium. And one year mortality in Chinese geriatric undergoing noncardiac surgery patients study protocol for a prospective observational cohort study.

Thank you for writing. This protocol for this. Trial. And I congratulate you for the great effort that you are putting in recruiting this number of patients to assess the impact of frailty on postoperative. Delirium after noncardiac surgery.

I believe the protocol is well constructed and well organized. My points are as follows.

1. I guess the status of surgery should be included. In the eligibility criteria. Whether you will include or exclude. Elective., or emergency surgery? I believe the status of surgery will have an impact on. The incidents. Of delirium in the post operative. So, this I guess should be clarified.

2. You mentioned that. A phone follow-up will be finished and any issues that develop within 30 days of the procedure will be noted. I guess in this point you should be clear about. The questions or that you will clarify with the patients because the type of answer depends on the question that you ask. So, is there any way that you mention two or three? Outcomes you will ask about in this follow up.

Otherwise. I have no. Concerns about this protocol. Thank you again for writing this. Protocol.

**********

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: Yes: salah eldien altarabsheh

**********

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PLoS One. 2024 Mar 6;19(3):e0295500. doi: 10.1371/journal.pone.0295500.r002

Author response to Decision Letter 0

10 May 2023

Dear Prof. Rose Ann Joyce Sagun Puetes:

Thank you for your letter and for your comments concerning our manuentitled “Correlation of preoperative frailty with postoperative delirium and one-year mortality in Chinese geriatric patients undergoing noncardiac surgery: a prospective observational cohort study” (ID: PONE-D-22-32948R1). Those comments are all valuable and very helpful for revising and improving our paper, as well as the important guiding significance to our researches. We have studied comments carefully and have made correction which we hope meet with approval. Revised portion are marked in red in the paper.

The main corrections in the paper and the responds to the reviewer’s comments are as flowing:

Journal Requirements:

We've checked your submission and before we can proceed, we need you to address the following issues:

1. Thank you for submitting your manuscript to PLOS ONE and for responding to our recent requests regarding your submission. Please accept our sincere apologies for the delay in responding to your query. As previously indicated, the CONSORT flow diagram in Figure 2 should be removed. This flow chart is used to show the number of participants excluded/included in the final analysis of a clinical trial. Since your manuscript describes work not yet completed, information on the number of participants included in the analysis cannot be provided. For this reason, it is not appropriate to include a CONSORT diagram in your manuscript. You may include a flow diagram to demonstrate your study design, but a CONSORT diagram is not appropriate for the purpose.

We suggest removing the flow diagram and relying on text in the Methods to describe the study design. Alternatively, you may provide a new diagram to illustrate your study design, but this should be based on the CONSORT diagram.

Response 1 We gratefully appreciate for your valuable suggestion/ comment. We have made changes based on your comments. We have already removed the CONSORT flow diagram. We have modified the "CONSORT flowchart" to the "Flow diagram of the study" and redone the diagram. We don't know if this modification meets the requirements. Can you give us some advice?

Fig. 2 Flow diagram of the study

In addition, one of our coauthors had a change of institution. I have changed the author's information, please know.

Min Zhang1†, Xiaojun Gao1†, Mengjie Liu1, Zhongquan Gao1,3, Xiaxuan Sun1,3, Linlin Huang4, Ting Zou4, Yongle Guo1,3, Lina Chen1, Yang Liu1, Xiaoning Zhang1, Hai Feng1, Yuelan Wang2,3, Yongtao Sun1*

1 Department of Anesthesiology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Institute of Anesthesia and Respiratory Critical Medicine, Jinan 250014, China

2 Department of Anesthesiology, Provincial Hospital Affiliated to Shandong First Medical University (Shandong Provincial Hospital), Jinan 250014, China

3 Department of Anesthesiology, Shandong First Medical University, Jinan 250014, China

4 Department of Nursing, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan 250014, China

*Corresponding author:

Yongtao Sun, Phone: +8618660795201, Email: ytsun@sdfmu.edu.cn

†These authors also contributed equally to this work.

Attachment

Submitted filename: Response to Editor 5.11.docx

pone.0295500.s003.docx^{(115.4KB, docx)}

PLoS One. doi: 10.1371/journal.pone.0295500.r003

Decision Letter 1

Silvia Fiorelli

25 Jul 2023

PONE-D-22-32948R1Correlation of preoperative frailty with postoperative delirium and one-year mortality in Chinese geriatric patients undergoing noncardiac surgery: study protocol for a prospective observational cohort studyPLOS ONE

Dear Dr. Sun,

==============================

ACADEMIC EDITOR:

I have specific concerns that this is a study protocol of a cohort study, but the authors have included elements of a clinical trial. The authors have included a study flowchart (Figures 2) that is still not suitable as they include numbers of participants or (n= ). This is not appropriate. If you include a flowchart it should only explain your study design. Please revise it accordingly. Alternatively, please remove Figure 2. In addition, in the revised version you do not appear to have provided a response specifically to the original reviewers’ comments. Please ensure that you provide this and a suitably marked up version of the manuscript highlighting how you have responded to all of the points raised (particularly by reviewer #1 in the original review).

==============================

Please submit your revised manuscript by Sep 08 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

We look forward to receiving your revised manuscript.

Kind regards,

Silvia Fiorelli

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

4. Have the authors described where all data underlying the findings will be made available when the study is complete?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

6. Review Comments to the Author

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: I didn't see any response or corrections to my comments. Therefore, I will leave the decision to the editors.

Reviewer #2: I have no comments . This paperwork looks good and I hope that data gathering and analysis will bring new findings

Reviewer #3: Dear the authors of the manuscript entitled "Correlation of preoperative frailty with postoperative delirium and one-year mortality in Chinese geriatric patients undergoing noncardiac surgery: study protocol for a

prospective observational cohort study"

Thank you for taking in consideration all the reviewers comments

I have no concerns about this manuscript

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

Reviewer #3: Yes: Salah Eldien Altarabsheh

**********

PLoS One. 2024 Mar 6;19(3):e0295500. doi: 10.1371/journal.pone.0295500.r004

Author response to Decision Letter 1

28 Jul 2023

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

Response 1 We are very sorry for our negligence of. We have made correction according to your comments.

Response 2 We are very sorry for our incorrect writing. Using the iThenticate/CrossCheck check tool, we verified our manuscript. We have already made revisions to the paper to remove the redundant content, cite your references, and explain how the present manuscript builds on earlier work. The percentage of text repetition dropped from 36% to 15%.

Response 3, We gratefully appreciate for your valuable suggestion/ comment. I'm sorry, but the cohort study's design was flawed. Under your guidance, we have learned the World Health Organization definition of a clinical trial. Therefore, we revised the manuscript again, studied relevant literature, and modified Figure 2 according to the cohort study. Your suggestions significantly enhanced our post. In this study, the link between preoperative frailty and POD was investigated in a group of Chinese patients aged 70 years or older undergoing noncardiac surgery. The reason for selecting this cohort is that their education level is generally low, which may be different from the world average. The relevance of this study is that we don't have any data on this issue.

1. Braga-Basaria M, Travison TG, Taplin ME, Lin A, Dufour AB, Habtemariam D, Nguyen PL, Kibel AS, Ravi P, Bearup R, Kackley H, Kafel H, Reid K, Storer T, Simonson DC, McDonnell M, Basaria S. Gaining metabolic insight in older men undergoing androgen deprivation therapy for prostate cancer (the ADT & Metabolism Study): Protocol of a longitudinal, observational, cohort study. PLoS One. 2023 Feb 10;18(2):e0281508. doi: 10.1371/journal.pone.0281508. PMID: 36763576.

2. Phillips S, Watt R, Atkinson T, et al. A protocol paper for the MOTION Study-A longitudinal study in a cohort aged 60 years and older to obtain mechanistic knowledge of the role of the gut microbiome during normal healthy ageing in order to develop strategies that will improve lifelong health and wellbeing. PLoS One. 2022;17(11):e0276118. Published 2022 Nov 18. doi:10.1371/journal.pone.0276118

4. We note that the grant information you provided in the ‘Funding Information’ and ‘Financial Disclosure’ sections do not match.

When you resubmit, please ensure that you provide the correct grant numbers for the awards you received for your study in the ‘Funding Information’ section.

Response 4 We are very sorry for our negligence of ‘Financial Disclosure’. We have matched the the ‘Funding Information’ and ‘Financial Disclosure’ according to your comments, please review.

5. Thank you for stating the following financial disclosure:

"The funders had and will not have a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."

At this time, please address the following queries:

a) Please clarify the sources of funding (financial or material support) for your study. List the grants or organizations that supported your study, including funding received from your institution.

c) If any authors received a salary from any of your funders, please state which authors and which funders.

d) If you did not receive any funding for this study, please state: “The authors received no specific funding for this work.”

Please include your amended statements within your cover letter; we will change the online submission form on your behalf.

Response 5 Thank you for your rigorous consideration. We have included our amended statements within cover letter and ‘Financial Disclosure’ (via Edit Submission) according to your advice.

6. Please amend the manuscript submission data (via Edit Submission) to include author Mengjie Liu.

Response 6 Thank you so much for your careful check. We have made correction according to your comments.

Response 7 We apologize for the inconvenience this has caused you. The ethics statement has already been relocated to the Methods section, Line 228-234.

Response 8 Thank you for your nice suggestion. On Lines 273-277, we have included Supporting Information.

Review Comments to the Author

It would be better if the authors could clarify following questions:

1. Please clarify the reason why the authors registered patients aged ≥ 70 years, not ≥ 60 or 65 years? In general, the elderly refers to people over the age of 65.

Response 1 We sincerely thank you for your insightful feedback. We had trouble figuring out age when we were planning this study. The age range for senile frailty study outcomes is now 65 or 70 years, with the majority of studies selecting the age range of 70 years. We ultimately settled on 70 years after reading through a substantial amount of literature and evaluating whether the research findings are unambiguous.

1. Morley JE, Vellas B, van Kan GA, et al. Frailty consensus: a call to action. J Am Med Dir Assoc. 2013;14(6):392-397. doi:10.1016/j.jamda.2013.03.022

2. Susano MJ, Grasfield RH, Friese M, et al. Brief Preoperative Screening for Frailty and Cognitive Impairment Predicts Delirium after Spine Surgery. Anesthesiology. 2020;133(6):1184-1191. doi:10.1097/ALN.0000000000003523

3. van Son, Joy E et al. “Atypical presentation of COVID-19 in older patients is associated with frailty but not with adverse outcomes.” European geriatric medicine, 1–11. 7 Feb. 2023, doi:10.1007/s41999-022-00736-z

2. Please clarify the participant registration was randomized or not.

Response 2 Thank you for your nice advice. We have made correction according to your comments, Line 101-102.

Response 3 We gratefully appreciate for your valuable suggestion and understand your concern. Modified frailty indexes included cardiac surgery bias in patients undergoing cardiac surgery. In addition, the incidence of POD in cardiac surgery patients is relatively high, which can reach 50%. Therefore, cardiac surgery and non-cardiac surgery are generally divided into two cohorts for study.

1. Ntalouka, Maria P et al. “The effect of type 2 diabetes mellitus on perioperative neurocognitive disorders in patients undergoing elective noncardiac surgery under general anesthesia. A prospective cohort study.” Journal of anaesthesiology, clinical pharmacology vol. 38,2 (2022): 252-262. doi:10.4103/joacp.JOACP_292_20

2. Bi, Xiaobo et al. “Effects of dexmedetomidine on neurocognitive disturbance after elective non-cardiac surgery in senile patients: a systematic review and meta-analysis.” The Journal of international medical research vol. 49,5 (2021): 3000605211014294. doi:10.1177/03000605211014294

Response 4 Thank you for your nice suggestion. We have added related references 32 and 33 and made correction according to your comments, Line 145-149.

Response 5 We sincerely thank you for your thoughtful advice. We apologize profusely for the surgical patients' negligence. We amended this section since the results of the preliminary study, which were utilized to determine the sample size, were for surgical patients, Line 111. In addition, the difference in incidence rate was due to the type of surgical patients selected. Previous studies did not take non-cardiac surgery patients as research objects, so the incidence rate was as high as 42-50%. In order to ensure the rigor of the trial, our preliminary results showed an incidence of about 23.0% in elderly patients with non-cardiac surgery in China. So there is a difference in incidence in the article.

Reviewer #2: This is a study protocol to investigate the Correlation of preoperative frailty with postoperative delirium and one-year mortality in Chinese geriatric undergoing noncardiac surgery patients: study protocol for a prospective observational cohort study.

At first the title has to be rearranged to:

Response 1 Thank you so much for your careful check. We have made correction according to your comments, Line 2.

In the abstract: rearrange the sentence: Frailty is associated with postoperative delirium (POD) but is rarely assessed undergoing noncardiac surgery patients.

To Frailty is associated with postoperative delirium (POD) but is rarely assessed in patients undergoing noncardiac surgery.

Response 2 Thank you for your rigorous consideration. We have made correction according to your comments, Line 20-21.

In the Abstract methods: (The study will be carried out in an operating room at a university hospital). This seems strange!

Response 3 Thank you. We are very sorry for our incorrect writing. We checked the manuscript carefully and found that this sentence was repeated with the following sentence, so it was deleted.

‘A total of 536 noncardiac surgery patients will be recruited from the First Affiliated Hospital of Shandong First Medical University for this study.’

In the Background: (More people are becoming patients than are getting older.) This is grammatically incorrect.

Response 4 It is really true as your suggested. We have changed the sentence to ‘Compared to aging, more people are getting sick’, Line 57-58.

Also, (the connection between preoperative frailty and the prevalence of POD, one-year mortality undergoing noncardiac surgery will be examined in this study), needs correction.

Response 5 Thank you. We have re-written this part according to your suggestion, Line 86-88.

In general, a reasonable study protocol

I believe the protocol is well constructed and well organized. My points are as follows.

Response 1 We gratefully appreciate for your valuable suggestion. We have added patients receiving elective non-cardiac surgery to clause 4 of the inclusion criteria. Moreover, add a third urgent surgery to the list of disqualifying factors. The design of this study selects non-cardiac surgery patients in the cohort, without distinguishing specific surgical methods. In the event of postoperative delirium, CAM-ICU will be used for assessment. With your professional advice, we have added CAM-ICU, Line33-35. Once again, I want to thank you for your expert guidance, which raised the article's level of excellence.

Response 2 Thank you for your valuable suggestion. Telephone interviews conducted 30 days after surgery asked about all-cause deaths, readmissions, repeat surgeries, tumor recurrences, cardiac arrest, etc.

Otherwise. I have no. Concerns about this protocol. Thank you again for writing this. Protocol.

We tried our best to improve the manu and made some changes in the manu. These changes will not influence the content and framework of the paper. And here we did not list the changes but marked in red in revised paper. We appreciate for Editors/Reviewers’ warm work earnestly, and hope that the

correction will meet with approval. Once again, thank you very much for your comments and suggestions.

Attachment

Submitted filename: Response to Editor.docx

pone.0295500.s004.docx^{(17.6KB, docx)}

PLoS One. doi: 10.1371/journal.pone.0295500.r005

Decision Letter 2

Silvia Fiorelli

6 Sep 2023

PONE-D-22-32948R2Correlation of preoperative frailty with postoperative delirium and one-year mortality in Chinese geriatric patients undergoing noncardiac surgery: study protocol for a prospective observational cohort studyPLOS ONE

Dear Dr. Sun,

==============================

ACADEMIC EDITOR:Thank you for carefully assess all reviewers points.I still have a specific comment on figure 2.

Since your manuscript describes work not yet completed, information on the number of

participants included in the analysis cannot be provided.

so you should remove all the patients numbers in this figure and leave " (n=)"

thank you

==============================

Please submit your revised manuscript by Oct 21 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

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Kind regards,

Silvia Fiorelli

Academic Editor

PLOS ONE

Journal Requirements:

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Yes

Reviewer #3: Yes

**********

2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

Reviewer #1: Yes

Reviewer #3: Yes

**********

3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Reviewer #1: Yes

Reviewer #3: Yes

**********

4. Have the authors described where all data underlying the findings will be made available when the study is complete?

Reviewer #1: Yes

Reviewer #3: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

Reviewer #1: Yes

Reviewer #3: Yes

**********

6. Review Comments to the Author

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors have responded to the comments point by point. I have no further comments.

(The uploaded manuscripts seem to be a bit confusing, there are three manuscripts in the pdf. Whether Fig2 was deleted or revised in the final version? and I saw that the editor suggested that the manuscript should be submitted as a Research Article, but R2 revision seems to be still a Study Protocol.)

Reviewer #3: Dear the authors

I read the revised version of the manuscript and your responses to the reviewers' comments.

I believe this manuscript in its current version stands in solid shape.

I have no concerns

**********

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Reviewer #1: No

Reviewer #3: Yes: salah eldien altarabsheh

**********

PLoS One. 2024 Mar 6;19(3):e0295500. doi: 10.1371/journal.pone.0295500.r006

Author response to Decision Letter 2

8 Sep 2023

Dear Academic Editor Silvia Fiorelli:

ACADEMIC EDITOR:

Thank you for carefully assess all reviewers points.

I still have a specific comment on figure 2.

Since your manuscript describes work not yet completed, information on the number of

participants included in the analysis cannot be provided.

so you should remove all the patients numbers in this figure and leave " (n=)".

Response 1: Thank you for the constructive comments and suggestions. We have removed remove all the patients numbers in this figure and leave " (n=)".

Attachment

Submitted filename: Response to Editor9.07.docx

pone.0295500.s005.docx^{(17.4KB, docx)}

PLoS One. doi: 10.1371/journal.pone.0295500.r007

Decision Letter 3

Silvia Fiorelli

24 Nov 2023

PONE-D-22-32948R3

Dear Dr. Sun,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Silvia Fiorelli

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #3: Yes

**********

2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

Reviewer #3: Yes

**********

3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Reviewer #3: Yes

**********

4. Have the authors described where all data underlying the findings will be made available when the study is complete?

Reviewer #3: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

Reviewer #3: Yes

**********

6. Review Comments to the Author

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #3: I am satisfied with the manuscript in its current version

Thnak you for considering all the reviewers comments

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #3: Yes: salah Eldien altarabsheh

**********

PLoS One. doi: 10.1371/journal.pone.0295500.r008

Acceptance letter

Silvia Fiorelli

25 Feb 2024

PONE-D-22-32948R3

PLOS ONE

Dear Dr. Sun,

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team.

At this stage, our production department will prepare your paper for publication. This includes ensuring the following:

* All references, tables, and figures are properly cited

* All relevant supporting information is included in the manuscript submission,

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on behalf of

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Academic Editor

PLOS ONE

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

S1 File. Study protocol English.

(DOC)

pone.0295500.s001.doc^{(61.2KB, doc)}

S2 File. Study protocol Chinese.

(DOC)

pone.0295500.s002.doc^{(72KB, doc)}

Attachment

Submitted filename: Response to Editor 5.11.docx

pone.0295500.s003.docx^{(115.4KB, docx)}

Attachment

Submitted filename: Response to Editor.docx

pone.0295500.s004.docx^{(17.6KB, docx)}

Attachment

Submitted filename: Response to Editor9.07.docx

pone.0295500.s005.docx^{(17.4KB, docx)}

Data Availability Statement

No datasets were generated or analysed during the current study. All relevant data from this study will be made available upon study completion.

[pone.0295500.ref001] 1.Chou MY, Wang YC, Peng LN, Liang CK, Chu CS, Liao MC, et al. Intraoperative blood transfusion predicts postoperative delirium among older patients undergoing elective orthopedic surgery: A prospective cohort study. Int J Geriatr Psychiatry. 2019;34(6):881–8. Epub 2019/02/15. doi: 10.1002/gps.5086 . [DOI] [PubMed] [Google Scholar]

[pone.0295500.ref002] 2.Oh ES, Fong TG, Hshieh TT, Inouye SK. Delirium in Older Persons: Advances in Diagnosis and Treatment. Jama. 2017;318(12):1161–74. Epub 2017/10/04. doi: 10.1001/jama.2017.12067 . [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0295500.ref003] 3.Inouye SK, Westendorp RG, Saczynski JS. Delirium in elderly people. Lancet. 2014;383(9920):911–22. Epub 2013/09/03. doi: 10.1016/S0140-6736(13)60688-1 . [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0295500.ref004] 4.Inouye SK. Delirium in older persons. N Engl J Med. 2006;354(11):1157–65. Epub 2006/03/17. doi: 10.1056/NEJMra052321 . [DOI] [PubMed] [Google Scholar]

[pone.0295500.ref005] 5.Etzioni DA, Liu JH, Maggard MA, Ko CY. The aging population and its impact on the surgery workforce. Ann Surg. 2003;238(2):170–7. Epub 2003/08/02. doi: 10.1097/01.SLA.0000081085.98792.3d . [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0295500.ref006] 6.Kojima G, Iliffe S, Jivraj S, Walters K. Association between frailty and quality of life among community-dwelling older people: a systematic review and meta-analysis. J Epidemiol Community Health. 2016;70(7):716–21. Epub 2016/01/20. doi: 10.1136/jech-2015-206717 . [DOI] [PubMed] [Google Scholar]

[pone.0295500.ref007] 7.Parmar KL, Law J, Carter B, Hewitt J, Boyle JM, Casey P, et al. Frailty in Older Patients Undergoing Emergency Laparotomy: Results From the UK Observational Emergency Laparotomy and Frailty (ELF) Study. Ann Surg. 2021;273(4):709–18. Epub 2019/06/13. doi: 10.1097/SLA.0000000000003402 . [DOI] [PubMed] [Google Scholar]

[pone.0295500.ref008] 8.Gómez Jiménez E, Avendaño Céspedes A, Cortés Zamora EB, García Molina R, Abizanda P. [Frailty prevalence in hospitalized older adults. A systematic review.]. Rev Esp Salud Publica. 2021;95. Epub 2021/10/09. . [PubMed] [Google Scholar]

[pone.0295500.ref009] 9.Penning Y, El Asmar A, Moreau M, Raspé J, Dal Lago L, Pepersack T, et al. Evaluation of the Comprehensive Geriatric Assessment (CGA) tool as a predictor of postoperative complications following major oncological abdominal surgery in geriatric patients. PLoS One. 2022;17(3):e0264790. Epub 2022/03/04. doi: 10.1371/journal.pone.0264790 . [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0295500.ref010] 10.Dent E, Martin FC, Bergman H, Woo J, Romero-Ortuno R, Walston JD. Management of frailty: opportunities, challenges, and future directions. Lancet. 2019;394(10206):1376–86. Epub 2019/10/15. doi: 10.1016/S0140-6736(19)31785-4 . [DOI] [PubMed] [Google Scholar]

[pone.0295500.ref011] 11.Fried LP, Ferrucci L, Darer J, Williamson JD, Anderson G. Untangling the concepts of disability, frailty, and comorbidity: implications for improved targeting and care. J Gerontol A Biol Sci Med Sci. 2004;59(3):255–63. Epub 2004/03/20. doi: 10.1093/gerona/59.3.m255 . [DOI] [PubMed] [Google Scholar]

[pone.0295500.ref012] 12.Robinson TN, Walston JD, Brummel NE, Deiner S, Brown CHt, Kennedy M, et al. Frailty for Surgeons: Review of a National Institute on Aging Conference on Frailty for Specialists. J Am Coll Surg. 2015;221(6):1083–92. Epub 2015/10/01. doi: 10.1016/j.jamcollsurg.2015.08.428 . [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0295500.ref013] 13.Huisman MG, Kok M, de Bock GH, van Leeuwen BL. Delivering tailored surgery to older cancer patients: Preoperative geriatric assessment domains and screening tools—A systematic review of systematic reviews. Eur J Surg Oncol. 2017;43(1):1–14. Epub 2016/07/14. doi: 10.1016/j.ejso.2016.06.003 . [DOI] [PubMed] [Google Scholar]

[pone.0295500.ref014] 14.Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet. 2013;381(9868):752–62. Epub 2013/02/12. doi: 10.1016/S0140-6736(12)62167-9 . [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0295500.ref015] 15.Dasgupta M, Rolfson DB, Stolee P, Borrie MJ, Speechley M. Frailty is associated with postoperative complications in older adults with medical problems. Arch Gerontol Geriatr. 2009;48(1):78–83. Epub 2007/12/11. doi: 10.1016/j.archger.2007.10.007 . [DOI] [PubMed] [Google Scholar]

[pone.0295500.ref016] 16.Lin HS, Watts JN, Peel NM, Hubbard RE. Frailty and post-operative outcomes in older surgical patients: a systematic review. BMC Geriatr. 2016;16(1):157. Epub 2016/09/02. doi: 10.1186/s12877-016-0329-8 . [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0295500.ref017] 17.Susano MJ, Grasfield RH, Friese M, Rosner B, Crosby G, Bader AM, et al. Brief Preoperative Screening for Frailty and Cognitive Impairment Predicts Delirium after Spine Surgery. Anesthesiology. 2020;133(6):1184–91. Epub 2020/09/09. doi: 10.1097/ALN.0000000000003523 . [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0295500.ref018] 18.Gracie TJ, Caufield-Noll C, Wang NY, Sieber FE. The Association of Preoperative Frailty and Postoperative Delirium: A Meta-analysis. Anesth Analg. 2021;133(2):314–23. Epub 2021/07/15. doi: 10.1213/ANE.0000000000005609 . [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0295500.ref019] 19.Schultz M, Rosted E, Sanders S. Frailty is associated with a history with more falls in elderly hospitalised patients. Dan Med J. 2015;62(6). Epub 2015/06/04. . [PubMed] [Google Scholar]

[pone.0295500.ref020] 20.Kojima G. Frailty as a Predictor of Future Falls Among Community-Dwelling Older People: A Systematic Review and Meta-Analysis. J Am Med Dir Assoc. 2015;16(12):1027–33. Epub 2015/08/10. doi: 10.1016/j.jamda.2015.06.018 . [DOI] [PubMed] [Google Scholar]

[pone.0295500.ref021] 21.Boyd CM, Xue QL, Simpson CF, Guralnik JM, Fried LP. Frailty, hospitalization, and progression of disability in a cohort of disabled older women. Am J Med. 2005;118(11):1225–31. Epub 2005/11/08. doi: 10.1016/j.amjmed.2005.01.062 . [DOI] [PubMed] [Google Scholar]

[pone.0295500.ref022] 22.Makary MA, Segev DL, Pronovost PJ, Syin D, Bandeen-Roche K, Patel P, et al. Frailty as a predictor of surgical outcomes in older patients. J Am Coll Surg. 2010;210(6):901–8. Epub 2010/06/01. doi: 10.1016/j.jamcollsurg.2010.01.028 . [DOI] [PubMed] [Google Scholar]

[pone.0295500.ref023] 23.McIsaac DI, Bryson GL, van Walraven C. Association of Frailty and 1-Year Postoperative Mortality Following Major Elective Noncardiac Surgery: A Population-Based Cohort Study. JAMA Surg. 2016;151(6):538–45. Epub 2016/01/23. doi: 10.1001/jamasurg.2015.5085 . [DOI] [PubMed] [Google Scholar]

[pone.0295500.ref024] 24.Kulmala J, Nykänen I, Hartikainen S. Frailty as a predictor of all-cause mortality in older men and women. Geriatr Gerontol Int. 2014;14(4):899–905. Epub 2014/03/29. doi: 10.1111/ggi.12190 . [DOI] [PubMed] [Google Scholar]

[pone.0295500.ref025] 25.Lee DH, Buth KJ, Martin BJ, Yip AM, Hirsch GM. Frail patients are at increased risk for mortality and prolonged institutional care after cardiac surgery. Circulation. 2010;121(8):973–8. Epub 2010/02/18. doi: 10.1161/CIRCULATIONAHA.108.841437 . [DOI] [PubMed] [Google Scholar]

[pone.0295500.ref026] 26.Chow WB, Rosenthal RA, Merkow RP, Ko CY, Esnaola NF. Optimal preoperative assessment of the geriatric surgical patient: a best practices guideline from the American College of Surgeons National Surgical Quality Improvement Program and the American Geriatrics Society. J Am Coll Surg. 2012;215(4):453–66. Epub 2012/08/25. doi: 10.1016/j.jamcollsurg.2012.06.017 . [DOI] [PubMed] [Google Scholar]

[pone.0295500.ref027] 27.Aldecoa C, Bettelli G, Bilotta F, Sanders RD, Audisio R, Borozdina A, et al. European Society of Anaesthesiology evidence-based and consensus-based guideline on postoperative delirium. Eur J Anaesthesiol. 2017;34(4):192–214. Epub 2017/02/12. doi: 10.1097/EJA.0000000000000594 . [DOI] [PubMed] [Google Scholar]

[pone.0295500.ref028] 28.Gill TM, Gahbauer EA, Han L, Allore HG. Trajectories of disability in the last year of life. N Engl J Med. 2010;362(13):1173–80. Epub 2010/04/02. doi: 10.1056/NEJMoa0909087 . [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0295500.ref029] 29.Amini S, Crowley S, Hizel L, Arias F, Libon DJ, Tighe P, et al. Feasibility and Rationale for Incorporating Frailty and Cognitive Screening Protocols in a Preoperative Anesthesia Clinic. Anesth Analg. 2019;129(3):830–8. Epub 2019/08/20. doi: 10.1213/ANE.0000000000004190 . [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0295500.ref030] 30.Mou Q, Gao M, Liu X, Wei C, Lan G, Zhao X, et al. Preoperative anxiety as an independent predictor of postoperative delirium in older patients undergoing elective surgery for lumbar disc herniation. Aging Clin Exp Res. 2023;35(1):85–90. Epub 2022/10/20. doi: 10.1007/s40520-022-02278-7 . [DOI] [PubMed] [Google Scholar]

[pone.0295500.ref031] 31.Chan AW, Tetzlaff JM, Altman DG, Laupacis A, Gøtzsche PC, Krle AJK, et al. SPIRIT 2013 Statement: defining standard protocol items for clinical trials. Rev Panam Salud Publica. 2015;38(6):506–14. Epub 2016/07/22. . [PMC free article] [PubMed] [Google Scholar]

[pone.0295500.ref032] 32.Velanovich V, Antoine H, Swartz A, Peters D, Rubinfeld I. Accumulating deficits model of frailty and postoperative mortality and morbidity: its application to a national database. J Surg Res. 2013;183(1):104–10. Epub 2013/02/19. doi: 10.1016/j.jss.2013.01.021 . [DOI] [PubMed] [Google Scholar]

[pone.0295500.ref033] 33.Subramaniam S, Aalberg JJ, Soriano RP, Divino CM. New 5-Factor Modified Frailty Index Using American College of Surgeons NSQIP Data. J Am Coll Surg. 2018;226(2):173–81.e8. Epub 2017/11/21. doi: 10.1016/j.jamcollsurg.2017.11.005 . [DOI] [PubMed] [Google Scholar]

[pone.0295500.ref034] 34.Katiyar V, Sharma R, Tandon V, Goda R, Ganeshkumar A, Suri A, et al. Impact of frailty on surgery for glioblastoma: a critical evaluation of patient outcomes and caregivers’ perceptions in a developing country. Neurosurg Focus. 2020;49(4):E14. Epub 2020/10/02. doi: 10.3171/2020.7.FOCUS20482 . [DOI] [PubMed] [Google Scholar]

[pone.0295500.ref035] 35.Marcantonio ER, Ngo LH, O’Connor M, Jones RN, Crane PK, Metzger ED, et al. 3D-CAM: derivation and validation of a 3-minute diagnostic interview for CAM-defined delirium: a cross-sectional diagnostic test study. Ann Intern Med. 2014;161(8):554–61. doi: 10.7326/M14-0865 . [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0295500.ref036] 36.Yu R, Wong M, Chong KC, Chang B, Lum CM, Auyeung TW, et al. Trajectories of frailty among Chinese older people in Hong Kong between 2001 and 2012: an age-period-cohort analysis. Age Ageing. 2018;47(2):254–61. doi: 10.1093/ageing/afx170 . [DOI] [PubMed] [Google Scholar]

[pone.0295500.ref037] 37.Mousa A, Savva GM, Mitnitski A, Rockwood K, Jagger C, Brayne C, et al. Is frailty a stable predictor of mortality across time? Evidence from the Cognitive Function and Ageing Studies. Age Ageing. 2018;47(5):721–7. doi: 10.1093/ageing/afy077 . [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0295500.ref038] 38.Ilinca S, Calciolari S. The patterns of health care utilization by elderly Europeans: frailty and its implications for health systems. Health Serv Res. 2015;50(1):305–20. Epub 20140819. doi: 10.1111/1475-6773.12211 . [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0295500.ref039] 39.Hoogendijk EO, Muntinga ME, van Leeuwen KM, van der Horst HE, Deeg DJ, Frijters DH, et al. Self-perceived met and unmet care needs of frail older adults in primary care. Arch Gerontol Geriatr. 2014;58(1):37–42. Epub 20130912. doi: 10.1016/j.archger.2013.09.001 . [DOI] [PubMed] [Google Scholar]

[pone.0295500.ref040] 40.Vermeiren S, Vella-Azzopardi R, Beckwée D, Habbig AK, Scafoglieri A, Jansen B, et al. Frailty and the Prediction of Negative Health Outcomes: A Meta-Analysis. J Am Med Dir Assoc. 2016;17(12):1163.e1-.e17. doi: 10.1016/j.jamda.2016.09.010 . [DOI] [PubMed] [Google Scholar]

[pone.0295500.ref041] 41.Yang X, Lupón J, Vidán MT, Ferguson C, Gastelurrutia P, Newton PJ, et al. Impact of Frailty on Mortality and Hospitalization in Chronic Heart Failure: A Systematic Review and Meta-Analysis. J Am Heart Assoc. 2018;7(23):e008251. doi: 10.1161/JAHA.117.008251 . [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0295500.ref042] 42.Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56(3):M146–56. Epub 2001/03/17. doi: 10.1093/gerona/56.3.m146 . [DOI] [PubMed] [Google Scholar]

[pone.0295500.ref043] 43.Junius-Walker U, Onder G, Soleymani D, Wiese B, Albaina O, Bernabei R, et al. The essence of frailty: A systematic review and qualitative synthesis on frailty concepts and definitions. Eur J Intern Med. 2018;56:3–10. Epub 20180531. doi: 10.1016/j.ejim.2018.04.023 . [DOI] [PubMed] [Google Scholar]

[pone.0295500.ref044] 44.Tanaka S, Ueno M, Iida H, Kaibori M, Nomi T, Hirokawa F, et al. Preoperative assessment of frailty predicts age-related events after hepatic resection: a prospective multicenter study. J Hepatobiliary Pancreat Sci. 2018;25(8):377–87. Epub 20180723. doi: 10.1002/jhbp.568 . [DOI] [PubMed] [Google Scholar]

[pone.0295500.ref045] 45.Morley JE, Vellas B, van Kan GA, Anker SD, Bauer JM, Bernabei R, et al. Frailty consensus: a call to action. J Am Med Dir Assoc. 2013;14(6):392–7. doi: 10.1016/j.jamda.2013.03.022 . [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0295500.ref046] 46.Rockwood K, Mitnitski A. Frailty defined by deficit accumulation and geriatric medicine defined by frailty. Clin Geriatr Med. 2011;27(1):17–26. doi: 10.1016/j.cger.2010.08.008 . [DOI] [PubMed] [Google Scholar]

[pone.0295500.ref047] 47.Xue QL. The frailty syndrome: definition and natural history. Clin Geriatr Med. 2011;27(1):1–15. doi: 10.1016/j.cger.2010.08.009 . [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0295500.ref048] 48.Dent E, Kowal P, Hoogendijk EO. Frailty measurement in research and clinical practice: A review. Eur J Intern Med. 2016;31:3–10. Epub 20160331. doi: 10.1016/j.ejim.2016.03.007 . [DOI] [PubMed] [Google Scholar]

PERMALINK

Correlation of preoperative frailty with postoperative delirium and one-year mortality in Chinese geriatric patients undergoing noncardiac surgery: Study protocol for a prospective observational cohort study

Min Zhang

Xiaojun Gao

Mengjie Liu

Zhongquan Gao

Xiaxuan Sun

Linlin Huang

Ting Zou

Yongle Guo

Lina Chen

Yang Liu

Xiaoning Zhang

Hai Feng

Yuelan Wang

Yongtao Sun

Roles

Abstract

Background

Methods

Discussion

Trial registration

Background

Methods/Design

Fig 1. Timeline and schedule for enrolment, allocation, and assessments.

Fig 2. Flow diagram of the study.

Participants

Sample size calculation

Eligibility criteria

Table 1. Inclusion and exclusion criteria.

Shedding criteria

Study implementation

Primary outcome

Secondary outcomes

Participant timeline

Recruitment

Data collection methods

Data management

Patient and public participation

Statistical methods

Ethics approval and consent to participate

Discussion

Trial status

Supporting information

Abbreviations

Data Availability

Funding Statement

References

Decision Letter 0

Walid Kamal Abdelbasset

Roles

Author response to Decision Letter 0

Decision Letter 1

Silvia Fiorelli

Roles

Author response to Decision Letter 1

Decision Letter 2

Silvia Fiorelli

Roles

Author response to Decision Letter 2

Decision Letter 3

Silvia Fiorelli

Roles

Acceptance letter

Silvia Fiorelli

Roles

Associated Data

Supplementary Materials

Data Availability Statement

ACTIONS

PERMALINK

RESOURCES

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