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The Clinical Respiratory Journal May 2024This meta-analysis sought to investigate the effect of neoadjuvant chemotherapy (NACT) combined with surgery in patients with nonsmall cell lung cancer (NSCLC). (Meta-Analysis)
Meta-Analysis
INTRODUCTION
This meta-analysis sought to investigate the effect of neoadjuvant chemotherapy (NACT) combined with surgery in patients with nonsmall cell lung cancer (NSCLC).
METHODS
With time span from January 2010 to December 2022, PubMed, Web of Science and Embase, China National Knowledge Infrastructure, and WanFang databases were searched for randomized controlled trials on comparison between NACT combined with surgery and surgery alone in patients with NSCLC. Then a meta-analysis was performed in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS
A total of 1511 studies were retrieved and 12 were finally included. Meta-analysis results showed that compared with surgery alone, a combination of NACT and surgery was associated with higher treatment response rate (odds ratio, OR = 2.459, 95% confidence interval, CI [1.785, 3.388], P < 0.001), 1-year survival rate (OR = 2.185, 95% CI [1.608, 2.970], P < 0.001), and 3-year survival rate (OR = 2.195, 95% CI [1.568, 3.073], P < 0.001) and lower levels of intraoperative blood loss (standardized mean difference, SMD = -0.932, 95% CI [-1.588, -0.275], P = 0.005) and length of hospital stay (SMD = -0.481, 95% CI [-0.933, -0.028], P = 0.037).
CONCLUSION
NACT combined with surgery is superior to surgery alone in the treatment of NSCLC and can promote postoperative recovery. Collectively, such combination is a safe and effective treatment for patients with NSCLC.
Topics: Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms; Neoadjuvant Therapy; Pneumonectomy; Survival Rate; Treatment Outcome; Chemotherapy, Adjuvant; Randomized Controlled Trials as Topic; Length of Stay; Female; Combined Modality Therapy
PubMed: 38725310
DOI: 10.1111/crj.13756 -
European Respiratory Review : An... Apr 2024Lung cancer diagnosis, staging and treatment may be enhanced by multidisciplinary participation and presentation in multidisciplinary meetings (MDM). We performed a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Lung cancer diagnosis, staging and treatment may be enhanced by multidisciplinary participation and presentation in multidisciplinary meetings (MDM). We performed a systematic review and meta-analysis to explore literature evidence of clinical impacts of MDM exposure.
METHODS
A study protocol was registered (PROSPERO identifier CRD42021258069). Randomised controlled trials and observational cohort studies including adults with nonsmall cell lung cancer and who underwent MDM review, compared to no MDM, were included. MEDLINE, CENTRAL, Embase and ClinicalTrials.gov were searched on 31 May 2021. Studies were screened and extracted by two reviewers. Outcomes included time to diagnosis and treatment, histological confirmation, receipt of treatments, clinical trial participation, survival and quality of life. Risk of bias was assessed using the ROBINS-I (Risk of Bias in Non-randomised Studies - of Interventions) tool.
RESULTS
2947 citations were identified, and 20 studies were included. MDM presentation significantly increased histological confirmation of diagnosis (OR 3.01, 95% CI 2.30-3.95; p<0.00001) and availability of clinical staging (OR 2.55, 95% CI 1.43-4.56; p=0.002). MDM presentation significantly increased likelihood of receipt of surgery (OR 2.01, 95% CI 1.29-3.12; p=0.002) and reduced the likelihood of receiving no active treatment (OR 0.32, 95% CI 0.21-0.50; p=0.01). MDM presentation was protective of both 1-year survival (OR 3.23, 95% CI 2.85-3.68; p<0.00001) and overall survival (hazard ratio 0.63, 95% CI 0.55-0.72; p<0.00001).
DISCUSSION
MDM presentation was associated with increased likelihood of histological confirmation of diagnosis, documentation of clinical staging and receipt of surgery. Overall and 1-year survival was better in those presented to an MDM, although there was some clinical heterogeneity in participants and interventions delivered. Further research is required to determine the optimal method of MDM presentation, and address barriers to presentation.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Patient Care Team; Interdisciplinary Communication; Neoplasm Staging; Treatment Outcome
PubMed: 38719736
DOI: 10.1183/16000617.0157-2023 -
Frontiers in Immunology 2024The efficacy and safety of different immunosuppressants combined with chemotherapy in treating patients with small-cell lung cancer (extensive-disease small-cell lung... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The efficacy and safety of different immunosuppressants combined with chemotherapy in treating patients with small-cell lung cancer (extensive-disease small-cell lung cancer, limited-disease small-cell lung cancer and relapsed small-cell lung cancer) are still unknown, and there are no reports directly comparing the efficacy and safety of other immunotherapies.
OBJECTIVE
This study aimed to compare the efficacy and safety of first-line immunotherapy combined with chemotherapy in patients with small-cell lung cancer.
METHOD
We searched Pubmed, Embase, Cochrane Library, CNKI, and Wanfang databases for relevant articles published from inception to November 11, 2020. The risk of bias of the included studies was conducted using the Cochrane risk-of-bias (RoB) tool. Multiple Bayesian network meta-analyses were performed. They conducted data analysis using R Studio and STATA version 15.1. The outcomes comprised overall survival (OS), progression-free survival (PFS), stability of response (SOR), duration of response (DOR) and adverse events of grade 3 or higher (AE grade≥3). A 95% confidence interval (CI) was provided for each estimate.
RESULTS
This meta-analysis included 16 RCT studies with 5898 patients. For OS, relative to chemotherapy (MD=-4.49; 95%CI [-7.97, -1.03]), durvalumab plus tremelimumab (MD=-4.62; 95%CI [-9.08, -0.11]), ipilimumab (MD=-4.26; 95%CI [-8.01, -0.3]) and nivolumab(MD=-5.66; 95%CI [-10.44, -1.11]) and nivolumab plus ipilimumab (MD=-4.56; 95%CI [-8.7, -0.1]), serplulimab can significantly increase the OS of SCLC patients. There was no significant difference between PFS, SOR and DOR. Analysis of AE showed that different immunotherapy combined chemotherapy regimens were similar to single chemotherapy regarding the overall incidence of AE grade≥3. However, after the cumulative ranking of the common symptoms of different adverse reactions, it was found that nivolumab ranked first in the occurrence probability of anemia (99.08%), fatigue (84.78%), and decreased appetite (89.66%). durvalumab was the most likely in nausea (75.4%). Pembrolizumab (76.24%) was most likely to cause pruritus. Chemotherapy combined with immunotherapy caused less diarrhea than chemotherapy alone (80.16%).
CONCLUSIONS
According to our analysis, serplulimab combined with chemotherapy is more likely to show better efficacy with a manageable safety profile for small-cell lung cancer. However, the evidence for this comparison shows some limitations due to the number of literature.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023486053.
Topics: Humans; Small Cell Lung Carcinoma; Lung Neoplasms; Network Meta-Analysis; Antineoplastic Combined Chemotherapy Protocols; Immunotherapy; Treatment Outcome; Immune Checkpoint Inhibitors
PubMed: 38694505
DOI: 10.3389/fimmu.2024.1362537 -
Journal of Cancer Research and... Apr 2024The incidence of thromboembolic events (TEs) in non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs) has rarely been reported.... (Meta-Analysis)
Meta-Analysis
The incidence of thromboembolic events (TEs) in non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs) has rarely been reported. The MEDLINE, EMBASE, and the Cochrane Library databases were searched. The primary outcome was the incidence of TEs, and the secondary outcome was the relationship between TEs and overall survival (OS) following ICI therapy. A subgroup analysis of TE incidents was performed according to the TE type and combination regimens. The I2 statistic was used to determine the heterogeneity, and funnel plots and Egger's test were used to assess publication bias. A total of 16,602 patients with NSCLC in 63 experimental arms were included in the analysis. The rate of TEs ranged from 0.1% to 13.8%, and the pooled overall incidence of all-grade TEs was 3% (95% confidence interval [CI], 2%-4%). The pooled rate of high-grade TEs was 1% (95% CI, 1%-2%). The venous and arterial TE rates were 3% (95% CI, 2%-4%) and 1% (95% CI, 1%-2%), respectively. Patients who received immunotherapy + chemoradiotherapy had the highest incidence of TEs (7%). The TE pooled rate was higher in patients treated with combined ICIs than in those treated with mono ICIs (4% vs. 2%). The OS was lower in patients with TEs than in those without TEs (hazard ratio, 1.4; 95% CI, 1.02%-1.92%). The incidence of TEs in NSCLC patients treated with ICIs was reasonable. Nonetheless, clinicians must be aware of potential thrombotic complications and treat them promptly.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Immune Checkpoint Inhibitors; Lung Neoplasms; Incidence; Thromboembolism
PubMed: 38687920
DOI: 10.4103/jcrt.jcrt_1031_23 -
BMC Cancer Apr 2024Although numerous studies have reported the prognostic value of the lung immune prognostic index (LIPI) in non-small cell lung cancer (NSCLC) patients treated with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although numerous studies have reported the prognostic value of the lung immune prognostic index (LIPI) in non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs), the prognostic value of the LIPI in a pancancer setting remains unclear.
METHODS
A comprehensive search was conducted until July 2023 across the PubMed, Embase, Web of Science, and Cochrane Library databases to identify relevant studies evaluating the prognostic value of the LIPI in cancer patients treated with ICIs. The outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). We described and compared the pooled outcomes by stratifying the patients based on different groupings of LIPI (good vs. intermediate [0 vs. 1], good vs. poor [0 vs. 2], and good vs. intermediate / poor [0 vs. 1 + 2]).
RESULTS
A total of 9959 patients in 35 studies were included. A higher score of LIPI was associated with impaired OS. The pooled HRs were 1.69 (95% CI: 1.55-1.85, p < 0.001; 0 vs. 1), 3.03 (95% CI: 2.53-3.63, p < 0.001; 0 vs. 2), and 2.38 (95% CI: 1.97-2.88, p < 0.001; 0 vs. 1 + 2). A higher LIPI score was associated with shorter PFS. The pooled HRs were 1.41 (95% CI: 1.31-1.52, p < 0.001; 0 vs. 1), 2.23 (95% CI: 1.87-2.66, p < 0.001; 0 vs. 2), and 1.65 (95% CI: 1.46-1.86, p < 0.001; 0 vs. 1 + 2). Similarly, a higher LIPI score was associated with a lower ORR. The pooled ORs were 0.63 (95% CI: 0.54-0.75, p < 0.001; 0 vs. 1) and 0.38 (95% CI: 0.29-0.50, p < 0.001; 0 vs. 2). A higher LIPI score was associated with a lower DCR. The pooled ORs were 0.47 (95% CI: 0.35-0.61, p < 0.001; 0 vs. 1) and 0.19 (95% CI: 0.12-0.30, p < 0.001; 0 vs. 2).
CONCLUSION
In patients with NSCLC or other solid tumours, the lung immune prognostic index could robustly stratify the clinical outcomes into three groups among the patients who receive ICIs. LIPI is a low-cost, simple, accessible, and accurate prognostic tool in a pancancer setting and it may contribute to the evaluation of risk stratification in patients treated with ICIs.
Topics: Humans; Immune Checkpoint Inhibitors; Prognosis; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Progression-Free Survival
PubMed: 38664760
DOI: 10.1186/s12885-024-12271-0 -
Frontiers in Immunology 2024At present, several important trials have been published show that perioperative immunotherapy combined with chemotherapy can improve the prognosis of patients with... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of neoadjuvant immunotherapy plus chemotherapy followed by adjuvant immunotherapy in resectable non-small cell lung cancer: a meta-analysis of phase 3 clinical trials.
OBJECTIVE
At present, several important trials have been published show that perioperative immunotherapy combined with chemotherapy can improve the prognosis of patients with resectable non-small cell lung cancer, which further optimizes treatment options. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of perioperative immunotherapy combined with chemotherapy in resectable non-small cell lung cancer.
METHODS
The following databases were searched for relevant studies: PubMed, EMBASE, Cochrane library (updated 12 October 2023). All randomized trials comparing perioperative immunotherapy combined with chemotherapy versus chemotherapy alone in resectable non-small cell lung cancer were eligible for inclusion. Data were analyzed using Review Manager 5.4.1 (Cochrane collaboration software). Primary outcomes and measures included overall survival (OS), event-free survival (EFS), pathological complete response (pCR), major pathological response (MPR), R0 resection rate, rate of underwent surgery and adverse events (AEs).
RESULTS
A total of 2912 patients (1453 receiving perioperative immunotherapy plus chemotherapy and 1459 receiving chemotherapy alone) were included in this systematic review and meta-analysis. The result showed that compared with chemotherapy alone, combined therapy significantly improved OS (HR = 0.68;95% CI: 0.56-0.83), EFS (HR = 0.58;95% CI: 0.51-0.65), pCR (OR = 7.53;95% CI: 4.63-12.26), MPR (OR = 5.03;95% CI: 3.40-7.44), R0 resection (OR = 1.58;95% CI: 1.152.18) and rate of underwent surgery (OR = 1.25;95% CI: 1.04-1.49). However, combination therapy was associated with higher risk of severe adverse event (OR = 1.46;95% CI: 1.19-1.78; P=0.0002), grade 3 and higher treatment-related adverse event (TRAE) (OR = 1.25;95% CI: 1.06-1.49; P=0.010), TRAE that led to interruption (OR = 1.90;95% CI: 1.34-2.68; P=0.0003) and immune-related adverse event (OR = 2.78;95% CI: 2.18-3.55; P<0.00001). Significant benefits were observed across most subgroups of EFS and pCR. However, no statistical differences were observed for EFS of never smoked (HR = 0.73;95% CI: 0.51-1.05) and EGFR-mutation positive (HR = 0.35;95% CI: 0.04-3.03).
CONCLUSION
This systematic review and meta-analysis found superior efficacy associated with perioperative immunotherapy plus chemotherapy compared with chemotherapy alone in both tumor regression and prolonged survival in resectable NSCLC, but increased the risk of TRAE, so monitoring for adverse events is warranted.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero, identifier (CRD42023476786).
Topics: Humans; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chemotherapy, Adjuvant; Clinical Trials, Phase III as Topic; Combined Modality Therapy; Immunotherapy; Lung Neoplasms; Neoadjuvant Therapy; Treatment Outcome
PubMed: 38646542
DOI: 10.3389/fimmu.2024.1359302 -
JAMA Network Open Apr 2024Randomized clinical trials (RCTs) with neoadjuvant immune checkpoint inhibitors (ICIs) plus chemotherapy (ICI-chemotherapy) for patients with early-stage non-small cell... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Randomized clinical trials (RCTs) with neoadjuvant immune checkpoint inhibitors (ICIs) plus chemotherapy (ICI-chemotherapy) for patients with early-stage non-small cell lung cancer (NSCLC) have reported consistent associations with event-free survival (EFS) and pathologic complete response (pCR) pending longer follow-up for overall survival data.
OBJECTIVE
To assess the pooled benefit of ICI-chemotherapy in 2-year EFS and pCR among patients with NSCLC and examine the impact of clinical, pathologic, and treatment-related factors.
DATA SOURCES
Full-text articles and abstracts in English were searched in EMBASE, PubMed, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews through November 1, 2023, and in oncology conference proceedings from January 1, 2008, to November 1, 2023.
STUDY SELECTION
Phase 2 or 3 RCTs with neoadjuvant ICI-chemotherapy with or without adjuvant ICIs vs neoadjuvant chemotherapy alone with or without placebo or observation in patients with previously untreated NSCLC staged IB to IIIB were included.
DATA EXTRACTION AND SYNTHESIS
Data extraction of prespecified data elements was performed by 2 reviewers using a structured data abstraction electronic form. A random-effects model was used for meta-analysis. The meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline.
MAIN OUTCOMES AND MEASURES
Two-year EFS and pCR were the outcomes of interest in patients who received neoadjuvant ICI-chemotherapy (experimental arm) or neoadjuvant chemotherapy alone (control arm). Aggregated pooled hazard ratios (HRs) for time-to-event outcomes (2-year EFS) and risk ratios (RRs) for dichotomous outcomes (pCR) with their respective 95% CIs were calculated.
RESULTS
Eight trials with 3387 patients were included, with some concerns of risk of bias as assessed by the Cochrane Collaboration method, mainly related to outcomes measurements. Neoadjuvant ICI-chemotherapy was associated with improved 2-year EFS (HR, 0.57; 95% CI, 0.50-0.66; P < .001) and increased pCR rate (RR, 5.58; 95% CI, 4.27-7.29; P < .001) in the experimental vs control treatment arms. This association was not significantly modified by the main patient characteristics; tumor- or treatment-related factors, including tumor programmed cell death ligand 1 (PD-L1) status; type of platinum-compound chemotherapy; number of cycles of neoadjuvant ICI-chemotherapy; or addition of adjuvant ICIs. Patients whose tumor cells were negative for PD-L1 were at higher risk of relapse (HR, 0.75; 95% CI, 0.62-0.91) than were those with low (HR, 0.61; 95% CI, 0.37-0.71) or high PD-L1 (HR, 0.40; 95% CI, 0.27-0.58) (P = .005).
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis of neoadjuvant ICI-chemotherapy RCTs in patients with early-stage NSCLC, 3 cycles of neoadjuvant platinum-based ICI-chemotherapy were associated with a meaningful improvement in 2-year EFS and pCR.
Topics: Humans; Neoadjuvant Therapy; Carcinoma, Non-Small-Cell Lung; B7-H1 Antigen; Neoplasm Recurrence, Local; Immunotherapy; Small Cell Lung Carcinoma; Adjuvants, Immunologic; Lung Neoplasms
PubMed: 38625698
DOI: 10.1001/jamanetworkopen.2024.6837 -
Clinical Lung Cancer Jun 2024A systematic literature review was conducted to determine the incidence and mortality of QT-interval prolongation (QTp), torsades de pointes (TdP), and heart failure... (Review)
Review
A systematic literature review was conducted to determine the incidence and mortality of QT-interval prolongation (QTp), torsades de pointes (TdP), and heart failure (HF) in patients with non-small cell lung cancer (NSCLC) who received epidermal growth factor receptor (EGFR) TKIs. Of 296 identified publications, 95 met eligibility criteria and were abstracted for QTp/TdP and HF outcomes (QTp/TdP: 83 publications, including 5 case study publications; HF: 79 publications, including 6 case study publications [involving 8 patients]). QTp incidence ranged from 0% to 27.8% in observational studies and from 0% to 11% in clinical trials, with no deaths due to QTp. There were no TdP events or deaths due to TdP. The incidence of HF ranged from 0% to 8%, and HF mortality rates ranged from 0% to 4%. Patients receiving treatment with EGFR TKIs should be monitored for signs of QTp, TdP, and HF per prescribing information. Standardized definitions and methods to improve monitoring of QTp, TdP, and HF-related events are needed in patients with NSCLC.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Heart Failure; Lung Neoplasms; ErbB Receptors; Torsades de Pointes; Protein Kinase Inhibitors; Long QT Syndrome; Incidence; Tyrosine Kinase Inhibitors
PubMed: 38553324
DOI: 10.1016/j.cllc.2024.02.005 -
Marine Drugs Feb 2024Non-small-cell lung cancer (NSCLC), the most commonly diagnosed cancer and the leading cause of cancer-related death worldwide, has been extensively investigated in the... (Review)
Review
Non-small-cell lung cancer (NSCLC), the most commonly diagnosed cancer and the leading cause of cancer-related death worldwide, has been extensively investigated in the last decade in terms of developing new therapeutic options that increase patient survival. In this context, marine animals are a source of new, interesting bioactive molecules that have been applied to the treatment of different types of cancer. Many efforts have been made to search for new therapeutic strategies to improve the prognosis of lung cancer patients, including new bioactive compounds and cytotoxic drugs from marine sponges. Their antitumoral effect can be explained by several cellular and molecular mechanisms, such as modulation of the cell cycle or induction of apoptosis. Thus, this systematic review aims to summarize the bioactive compounds derived from marine sponges and the mechanisms by which they show antitumor effects against lung cancer, exploring their limitations and the challenges associated with their discovery. The search process was performed in three databases (PubMed, SCOPUS, and Web of Science), yielding a total of 105 articles identified in the last 10 years, and after a screening process, 33 articles were included in this systematic review. The results showed that these natural sponge-derived compounds are a valuable source of inspiration for the development of new drugs. However, more research in this field is needed for the translation of these novel compounds to the clinic.
Topics: Animals; Humans; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Biological Products; Apoptosis; Porifera
PubMed: 38535442
DOI: 10.3390/md22030101 -
JNCI Cancer Spectrum Apr 2024Surrogate endpoints for overall survival in patients with resectable non-small cell lung cancer receiving neoadjuvant therapy are needed to provide earlier treatment... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Surrogate endpoints for overall survival in patients with resectable non-small cell lung cancer receiving neoadjuvant therapy are needed to provide earlier treatment outcome indicators and accelerate drug approval. This study's main objectives were to investigate the association among pathological complete response, major pathological response, event-free survival and overall survival and to determine whether treatment effects on pathological complete response and event-free survival correlate with treatment effects on overall survival.
METHODS
A comprehensive systematic literature review was conducted to identify neoadjuvant studies in resectable non-small cell lung cancer. Analysis at the patient level using frequentist and Bayesian random effects (hazard ratio [HR] for overall survival or event-free survival by pathological complete response or major pathological response status, yes vs no) and at the trial level using weighted least squares regressions (hazard ratio for overall survival or event-free survival vs pathological complete response, by treatment arm) were performed.
RESULTS
In both meta-analyses, pathological complete response yielded favorable overall survival compared with no pathological complete response (frequentist, 20 studies and 6530 patients: HR = 0.49, 95% confidence interval = 0.42 to 0.57; Bayesian, 19 studies and 5988 patients: HR = 0.48, 95% probability interval = 0.43 to 0.55) and similarly for major pathological response (frequentist, 12 studies and 1193 patients: HR = 0.36, 95% confidence interval = 0.29 to 0.44; Bayesian, 11 studies and 1018 patients: HR = 0.33, 95% probability interval = 0.26 to 0.42). Across subgroups, estimates consistently showed better overall survival or event-free survival in pathological complete response or major pathological response compared with no pathological complete response or no major pathological response. Trial-level analyses showed a moderate to strong correlation between event-free survival and overall survival hazard ratios (R2 = 0.7159) but did not show a correlation between treatment effects on pathological complete response and overall survival or event-free survival.
CONCLUSION
There was a strong and consistent association between pathological response and survival and a moderate to strong correlation between event-free survival and overall survival following neoadjuvant therapy for patients with resectable non-small cell lung cancer.
Topics: Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms; Neoadjuvant Therapy; Bayes Theorem; Progression-Free Survival; Treatment Outcome; Least-Squares Analysis; Disease-Free Survival; Proportional Hazards Models
PubMed: 38521542
DOI: 10.1093/jncics/pkae021