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Clinical Pharmacokinetics May 2024The establishment of optimal dosing regimens for intravenous (IV) lidocaine in the perioperative setting, aiming to balance effective pain relief with minimisation of...
BACKGROUND
The establishment of optimal dosing regimens for intravenous (IV) lidocaine in the perioperative setting, aiming to balance effective pain relief with minimisation of potential side effects, is a topic of ongoing debate. This discussion stems from the significant variability in lidocaine's pharmacokinetic (PK) parameters and its relatively narrow safety margin. Population pharmacokinetic (popPK) modelling has emerged as a valuable tool for understanding the factors contributing to this observed variability in drug kinetics.
OBJECTIVES
This systematic review compiles the existing knowledge on lidocaine's PK properties and published popPK models, with a focus on significant covariates.
METHODS
A systematic search on Cochrane CENTRAL, Medline, and EMBASE was performed from inception to June 2023. Original clinical studies that administered IV lidocaine to adults and performed PK analyses using a nonlinear mixed effects modelling approach were included. The quality of the included studies was assessed by compliance with the Clinical Pharmacokinetics (ClinPK) statement checklist.
RESULTS
Seven studies were included, which involved a diverse adult population, including both volunteers and patients with various comorbidities. Lidocaine PK was primarily characterised by a two- or three-compartment model. The volume of distribution at steady state ranged from 66 to 194 L, and the total clearance ranged from 22 to 49 L/h. Despite adjusting for significant covariates like heart failure status, alpha-1-acid glycoprotein, duration of lidocaine infusion, and body weight, each study revealed substantial variability in PK parameters. The potential impact of hepatic or renal function biomarkers on these PK parameters calls for further investigation. Incomplete reporting of key aspects of developed models may hinder the models' reliability and clinical application.
CONCLUSION
The findings emphasise the importance of tailoring drug dosage to ensure the safe and effective use of intravenous lidocaine. Optimal design methodologies may be incorporated for a more efficient identification of important covariates. Utilising contemporary model evaluation methods like visual predictive checks and bootstrapping would enhance the robustness of popPK models and the reliability of their predictions. This comprehensive review advances our understanding of lidocaine's pharmacokinetics and lays the groundwork for further research in this critical area of perioperative pain management. Review protocol registered on 25 August 2023 in PROSPERO (CRD42023441113). This work was supported by the Fundamental Research Grant Scheme, the Ministry of Higher Education, Malaysia (FRGS/1/2020/SKK01/UM/02/2).
Topics: Humans; Lidocaine; Anesthetics, Local; Adult; Models, Biological; Administration, Intravenous; Infusions, Intravenous
PubMed: 38703307
DOI: 10.1007/s40262-024-01373-4 -
Naunyn-Schmiedeberg's Archives of... May 2024It is estimated that cancer is the second leading cause of death worldwide. The primary or secondary cause of cancer-related mortality for women is breast cancer. The... (Review)
Review
It is estimated that cancer is the second leading cause of death worldwide. The primary or secondary cause of cancer-related mortality for women is breast cancer. The main treatment method for different types of cancer is chemotherapy with drugs. Because of less water solubility of chemotherapy drugs or their inability to pass through membranes, their body absorbs them inadequately, which lowers the treatment's effectiveness. Drug specificity and pharmacokinetics can be changed by nanotechnology using nanoparticles. Instead, targeted drug delivery allows medications to be delivered to the targeted sites. In this review, we focused on nanoparticles as carriers in targeted drug delivery, their characteristics, structure, and the previous studies related to breast cancer. It was shown that nanoparticles could reduce the negative effects of chemotherapy drugs while increasing their effectiveness. Lipid-based nanocarriers demonstrated notable results in this instance, and some products that are undergoing various stages of clinical trials are among the examples. Nanoparticles based on metal or polymers demonstrated a comparable level of efficacy. With the number of cancer cases rising globally, many researchers are now looking into novel treatment approaches, particularly the use of nanotechnology and nanoparticles in the treatment of cancer. In order to help clinicians, this article aimed to gather more information about various areas of nanoparticle application in breast cancer therapy, such as modifying their synthesis and physicochemical characterization. It also sought to gain a deeper understanding of the mechanisms underlying the interactions between nanoparticles and biologically normal or infected tissues.
PubMed: 38700795
DOI: 10.1007/s00210-024-03082-y -
PloS One 2024To systematically assess and compare the predictive value of the Ranson and Bedside Index of Severity in Acute Pancreatitis (BISAP) scoring systems for the severity and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To systematically assess and compare the predictive value of the Ranson and Bedside Index of Severity in Acute Pancreatitis (BISAP) scoring systems for the severity and prognosis of acute pancreatitis (AP).
METHODS
PubMed, Embase, Cochrane Library, and Web of Science were systematically searched until February 15, 2023. Outcomes in this analysis included severity and prognosis [mortality, organ failure, pancreatic necrosis, and intensive care unit (ICU) admission]. The revised Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool was used to evaluate the quality of diagnostic accuracy studies. The threshold effect was evaluated for each outcome. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the area under the summary receiver operating characteristic (SROC) curve (AUC) as well as 95% confidence intervals (CI) were calculated. The DeLong test was used for AUC comparisons. For the outcome evaluated by over 9 studies, publication bias was assessed using the Deeks' funnel plot asymmetry test.
RESULTS
Totally 17 studies of 5476 AP patients were included. For severity, the pooled sensitivity of the Ranson and BISAP was 0.95 (95%CI: 0.87, 0.98) and 0.67 (95%CI: 0.27, 0.92); the pooled specificity of the Ranson and BISAP was 0.74 (0.52, 0.88) and 0.95 (95%CI: 0.85, 0.98); the pooled AUC of the Ranson and BISAP was 0.95 (95%CI: 0.93, 0.97) and 0.94 (95%CI: 0.92, 0.96) (P = 0.480). For mortality, the pooled sensitivity of the Ranson and BISAP was 0.89 (95%CI: 0.73, 0.96) and 0.77 (95%CI: 0.58, 0.89); the pooled specificity of the Ranson and BISAP was 0.79 (95%CI: 0.68, 0.87) and 0.90 (95%CI: 0.86, 0.93); the pooled AUC of the Ranson and BISAP was 0.91 (95%CI: 0.88, 0.93) and 0.92 (95%CI: 0.90, 0.94) (P = 0.480). For organ failure, the pooled sensitivity of the Ranson and BISAP was 0.84 (95%CI: 0.76, 0.90) and 0.78 (95%CI: 0.60, 0.90); the pooled specificity of the Ranson and BISAP was 0.84 (95%CI: 0.63, 0.94) and 0.90 (95%CI: 0.72, 0.97); the pooled AUC of the Ranson and BISAP was 0.86 (95%CI: 0.82, 0.88) and 0.90 (95%CI: 0.87, 0.93) (P = 0.110). For pancreatic necrosis, the pooled sensitivity of the Ranson and BISAP was 0.63 (95%CI: 0.35, 0.84) and 0.63 (95%CI: 0.23, 0.90); the pooled specificity of the Ranson and BISAP was 0.90 (95%CI: 0.77, 0.96) and 0.93 (95%CI: 0.89, 0.96); the pooled AUC of the Ranson and BISAP was 0.87 (95%CI: 0.84, 0.90) and 0.93 (95%CI: 0.91, 0.95) (P = 0.001). For ICU admission, the pooled sensitivity of the Ranson and BISAP was 0.86 (95%CI: 0.77, 0.92) and 0.63 (95%CI: 0.52, 0.73); the pooled specificity of the Ranson and BISAP was 0.58 (95%CI: 0.55, 0.61) and 0.84 (95%CI: 0.81, 0.86); the pooled AUC of the Ranson and BISAP was 0.92 (95%CI: 0.81, 1.00) and 0.86 (95%CI: 0.67, 1.00) (P = 0.592).
CONCLUSION
The Ranson score was an applicable tool for predicting severity and prognosis of AP patients with reliable diagnostic accuracy in resource and time-limited settings. Future large-scale studies are needed to verify the findings.
Topics: Humans; Pancreatitis; Prognosis; Severity of Illness Index; Predictive Value of Tests; ROC Curve; Area Under Curve; Intensive Care Units
PubMed: 38687745
DOI: 10.1371/journal.pone.0302046 -
Paediatric Anaesthesia Apr 2024Age-related differences in the pharmacokinetics and pharmacodynamics of neuromuscular blocking agents (NMBAs) and the short duration of many surgical procedures put... (Review)
Review
Spontaneous recovery from neuromuscular block after a single dose of a muscle relaxant in pediatric patients: A systematic review using a network meta-analytic and meta-regression approach.
BACKGROUND
Age-related differences in the pharmacokinetics and pharmacodynamics of neuromuscular blocking agents (NMBAs) and the short duration of many surgical procedures put pediatric patients at risk of postoperative residual curarization (PORC). To date, the duration of neuromuscular blocking agent effect in children has not been analyzed in a quantitative review. The current meta-analysis aimed to compare spontaneous recovery following administration of various types and doses of neuromuscular blocking agents and to quantify the effect of prognostic variables associated with the recovery time in pediatric patients.
METHOD
We searched for randomized controlled trials (RCTs) and controlled clinical trials (CCTs) that compared the time to 25% T1 (t25), from 25% to 75% T1 (RI25-75), and to ≥90% train-of-four (tTOF90) neuromuscular recovery between common neuromuscular blocking agent treatments administered as a single bolus to healthy pediatric participants. We compared spontaneous t25, RI25-75, and tTOF90 between (1) neuromuscular blocking agent treatments and (2) age groups receiving a given neuromuscular blocking agent intervention and anesthesia technique. Bayesian random-effects network and pairwise meta-analyses along with meta-regression were used to evaluate the results.
RESULTS
We used data from 71 randomized controlled trials/controlled clinical trials including 4319 participants. Network meta-analysis allowed for the juxtaposition and ranking of spontaneous t25, RI25-75, and tTOF90 following common neuromuscular blocking agent interventions. For all neuromuscular blocking agents a log-linear relationship between dose and duration of action was found. With the neuromuscular blocking agent treatments studied, the average tTOF90 (mean[CrI95]) in children (>2-11 y) was 41.96 [14.35, 69.50] and 17.06 [5.99, 28.30] min shorter than in neonates (<28 d) and infants (28 d-12 M), respectively. We found a negative log-linear correlation between age and duration of neuromuscular blocking agent effect. The difference in the tTOF90 (mean[CrI95]) between children and other age groups increased by 21.66 [8.82, 34.53] min with the use of aminosteroid neuromuscular blocking agents and by 24.73 [7.92, 41.43] min with the addition of sevoflurane/isoflurane for anesthesia maintenance.
CONCLUSIONS
The times to neuromuscular recovery are highly variable. These can decrease significantly with age and are prolonged when volatile anesthetics are administered. This variability, combined with the short duration of many pediatric surgical procedures, makes quantitative neuromuscular monitoring mandatory even after a single dose of neuromuscular blocking agent.
PubMed: 38676354
DOI: 10.1111/pan.14908 -
Endocrine Apr 2024Growth hormone deficiency occurs when the pituitary gland does not produce enough growth hormone. Norditropin®, a recombinant human growth hormone, and Sogroya®, an... (Review)
Review
Efficacy, safety, and patient satisfaction of norditropin and sogroya in patients with growth hormone deficiency: a systematic review and meta-analysis of randomized controlled trials.
INTRODUCTION
Growth hormone deficiency occurs when the pituitary gland does not produce enough growth hormone. Norditropin®, a recombinant human growth hormone, and Sogroya®, an albumin-binding growth hormone derivative, are prescribed for patients with growth hormone deficiency. This systematic review assesses the efficacy, safety, and patient satisfaction associated with Norditropin and Sogroya.
METHODS
We systematically searched PubMed, Web of Science, and Scopus databases to identify eligible comparative studies. All studies published until June 2023 were included in our analysis. Our outcomes for children included height velocity and height velocity standard deviation score. In contrast, adult outcomes included adverse events, insulin-like growth factor 1-standard deviation score (IGF-1 SDS), and the Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9). Results are reported as odds ratio (OR) and mean difference (MD) with a 95% confidence interval (95% CI).
RESULTS
Ten studies involving 1058 participants (665 children and 393 adults) were included in the meta-analysis. In children, Norditropin at doses of 0.034 and 0.067 mg/kg/day was compared to Sogroya at doses of 0.04, 0.08, 0.16, and 0.24 mg/kg/week. The results showed that 0.034 mg/kg/day Norditropin had a favorable impact on height velocity (MD -2.01, 95% CI -3.7 to -2.12, p < 0.00001) and height velocity standard deviation score (Mean Difference -3.61, 95% CI -5.06 to -2.16, p < 0.00001) when compared to Sogroya 0.04 mg/kg/day. Other doses showed comparable results. In adults, the only significant side effect noted was rash, which favored Sogroya (OR 0.1, 95% CI 0.04-0.27, p < 0.00001). Additionally, IGF-1 SDS was significantly higher in the Sogroya group than in the Norditropin group (MD 0.25, 95% CI 0.02-0.48, p = 0.03). Furthermore, the overall score of the TSQM-9 questionnaire, which includes three domains: convenience, effectiveness, and satisfaction, was significantly higher in the Sogroya group compared to the Norditropin group (OR 6.36, 95% CI 3.92-8.8, p < 0.00001).
CONCLUSION
Norditropin and Sogroya showed comparable efficacy and safety profiles, except for the prevalence of rash in the Norditropin group, and Sogroya has higher satisfaction among adults. More high-quality studies with more patients are required to confirm these results.
PubMed: 38658475
DOI: 10.1007/s12020-024-03834-z -
Phytochemistry Jun 2024Forsythiae Fructus (FF), the dried fruit of F. suspensa, is commonly used to treat fever, inflammation, etc in China or other Asian countries. FF is usually used as the... (Review)
Review
Forsythiae Fructus (FF), the dried fruit of F. suspensa, is commonly used to treat fever, inflammation, etc in China or other Asian countries. FF is usually used as the core herb in traditional Chinese medicine preparations for the treatment of influenza, such as Shuang-huang-lian oral liquid and Yin-qiao powder, etc. Since the wide application and core role of FF, its research progress was summarized in terms of traditional uses, phytochemistry, pharmacology, pharmacokinetics, quality control, and toxicity. Meanwhile, the anti-influenza substances and mechanism of FF were emphasized. Till now, a total of 290 chemical components are identified in F. suspensa, and among them, 248 components were isolated and identified from FF, including 42 phenylethanoid glycosides, 48 lignans, 59 terpenoids, 14 flavonoids, 3 steroids, 24 cyclohexyl ethanol derivatives, 14 alkaloids, 26 organic acids, and 18 other types. FF and their pure compounds have the pharmacological activities of anti-virus, anti-inflammation, anti-oxidant, anti-bacteria, anti-tumor, neuroprotection, hepatoprotection, etc. Inhibition of TLR7, RIG-I, MAVS, NF-κB, MyD88 signaling pathway were the reported anti-influenza mechanisms of FF and phenylethanoid glycosides and lignans are the main active groups. However, the bioavailability of phenylethanoid glycosides and lignans of FF in vivo was low, which needed to be improved. Simultaneously, the un-elucidated compounds and anti-influenza substances of FF strongly needed to be explored. The current quality control of FF was only about forsythoside A and phillyrin, more active components should be taken into consideration. Moreover, there are no reports of toxicity of FF yet, but the toxicity of FF should be not neglected in clinical applications.
Topics: Forsythia; Quality Control; Humans; Fruit; Phytochemicals; Drugs, Chinese Herbal; Animals; Molecular Structure
PubMed: 38641141
DOI: 10.1016/j.phytochem.2024.114096 -
Paediatric Drugs May 2024In adults, sodium-glucose cotransporter type 2 inhibitors have revolutionised the treatment of type 2 diabetes mellitus, heart failure, and chronic kidney disease.
INTRODUCTION
In adults, sodium-glucose cotransporter type 2 inhibitors have revolutionised the treatment of type 2 diabetes mellitus, heart failure, and chronic kidney disease.
OBJECTIVE
We aimed to review information on compassionate use, clinical pharmacology, efficacy, and safety of dapagliflozin and empagliflozin in children.
METHODS
We conducted a systematic review of published clinical trials, case reports, and observational studies in Medline, Excerpta Medica, and Web of Science databases from inception to September 2023. For the two randomised controlled trials on type 2 diabetes mellitus (T2DM), we implemented a meta-analysis on the primary outcome (mean difference in glycosylated haemoglobin [HbA1c] between intervention and placebo groups). Review Manager (RevMan), version 5.4.1, was used for this purpose.
RESULTS
Thirty-five articles (nine case reports, ten case series, one prospective non-controlled trial, four controlled randomised trials, two surveys, six pharmacokinetic studies, and three pharmacovigilance studies) were selected, in which 415 children were exposed to either dapagliflozin or empagliflozin: 189 diabetic patients (mean age 14.7 ± 2.9 years), 32 children with glycogen storage disease type Ib (GSD Ib), glucose-6-phosphatase catalytic subunit 3 (G6PC3) deficiency, or severe congenital neutropenia type 4 (8.5 ± 5.1 years), 47 children with kidney disease or heart failure (11.2 ± 6.1 years), 84 patients in pharmacokinetic studies (15.1 ± 2.3 years), and 63 patients in toxicological series. The effect of dapagliflozin and empagliflozin in T2DM was demonstrated by HbA1c reduction in two randomised trials among a total of 177 adolescents, with a mean HbA1c difference of -0.82% (95% confidence interval -1.34 to -0.29) as compared to placebo (no heterogeneity, I = 0%). Dosage ranged between 5 and 20 mg (mean 11.4 ± 3.7) once daily for dapagliflozin and between 5 and 25 mg (mean 15.4 ± 7.4) once daily for empagliflozin. Among the paediatric cases of GSD Ib, empagliflozin 0.1-1.3 mg/kg/day improved neutropenia, infections, and gastrointestinal health. Dapagliflozin (mean dosage 6.9 ± 5.2 mg once daily) was well-tolerated in children with chronic kidney disease and heart failure. Side effects were generally mild, the most frequent being hypoglycaemia in children with GSD Ib (33% of patients) or T2DM (14% of patients) on concomitant hypoglycaemic drugs. Diabetic ketoacidosis is rare in children.
CONCLUSION
Early evidence suggests that dapagliflozin and empagliflozin are well tolerated in children. A clinical pharmacology rationale currently exists only for adolescents with diabetes mellitus.
PROSPERO REGISTRATION NUMBER
CRD42023438162.
Topics: Benzhydryl Compounds; Humans; Glucosides; Child; Diabetes Mellitus, Type 2; Sodium-Glucose Transporter 2 Inhibitors; Adolescent
PubMed: 38635113
DOI: 10.1007/s40272-024-00623-z -
Drug Development and Industrial Pharmacy May 2024TheDES are formed by mixing a Hydrogen Bond Donor (HBD) and a Hydrogen Bond Acceptor (HBA) in appropriate molar ratios. These solvents have been shown to enhance drug... (Review)
Review
OBJECTIVE
TheDES are formed by mixing a Hydrogen Bond Donor (HBD) and a Hydrogen Bond Acceptor (HBA) in appropriate molar ratios. These solvents have been shown to enhance drug solubility, permeability, and delivery. The main objective of the present article is to review these advantages of TheDES.
SIGNIFICANCE
TheDES show unique properties, such as low toxicity, biodegradability, improved bioavailability and enhanced drug delivery of poorly soluble active pharmaceutical ingredients. They are also biocompatible in nature which makes them a promising candidate for various therapeutic applications, including drug formulations, drug delivery and other biomedical uses. The development and utilization of TheDES shows significant advancement in pharmaceutical research, providing new opportunities for improving drug delivery.
METHODS
The current study was carried out by conducting a systematic literature review that identified relevant papers from indexed databases. Numerous studies and research are cited and quoted in this article to demonstrate the effectiveness of TheDES in enhancing drug solubility, permeability, and delivery. All chosen articles were selected considering their significance, quality, and approach to addressing issues.
RESULT
As a result, various TheDES were identified that can be formulated in different ways: one component can act as a vehicle for an API, either HBD or HBA can be an API, both HBD and HBA can be APIs, or the individual components of DES are not therapeutically active but the resulting DES possesses therapeutic activity. Additionally, TheDES were also recognized to enhance drug delivery and solubility for different APIs, including NSAIDs, anesthetic drugs, antifungals, and others.
Topics: Solubility; Deep Eutectic Solvents; Drug Delivery Systems; Permeability; Humans; Drug Compounding; Hydrogen Bonding; Chemistry, Pharmaceutical; Biological Availability; Pharmaceutical Preparations; Solvents
PubMed: 38634708
DOI: 10.1080/03639045.2024.2345131 -
Clinical and Translational Science Apr 2024N-acetyltransferase 2 (NAT2) genetic polymorphisms might alter isoniazid metabolism leading to toxicity. We reviewed the impact of NAT2 genotype status on the... (Review)
Review
N-acetyltransferase 2 (NAT2) genetic polymorphisms might alter isoniazid metabolism leading to toxicity. We reviewed the impact of NAT2 genotype status on the pharmacokinetics, efficacy, and safety of isoniazid, a treatment for tuberculosis (TB). A systematic search for research articles published in Scopus, PubMed, and Embase until August 31, 2023, was conducted without filters or limits on the following search terms and Boolean operators: "isoniazid" AND "NAT2." Studies were selected if NAT2 phenotypes with pharmacokinetics or efficacy or safety of isoniazid in patients with TB were reported. Patient characteristics, NAT2 status, isoniazid pharmacokinetic parameters, early treatment failure, and the prevalence of drug-induced liver injury were extracted. If the data were given as a median, these values were standardized to the mean. Forty-one pharmacokinetics and 53 safety studies were included, but only one efficacy study was identified. The average maximum concentrations of isoniazid were expressed as supratherapeutic concentrations in adults (7.16 ± 4.85 μg/mL) and children (6.43 ± 3.87 μg/mL) in slow acetylators. The mean prevalence of drug-induced liver injury was 36.23 ± 19.84 in slow acetylators, which was significantly different from the intermediate (19.49 ± 18.20) and rapid (20.47 ± 20.68) acetylators. Subgroup analysis by continent showed that the highest mean drug-induced liver injury prevalence was in Asian slow acetylators (42.83 ± 27.61). The incidence of early treatment failure was decreased by genotype-guided isoniazid dosing in one study. Traditional weight-based dosing of isoniazid in most children and adults yielded therapeutic isoniazid levels (except for slow acetylators). Drug-induced liver injury was more commonly observed in slow acetylators. Genotype-guided dosing may prevent early treatment failure.
Topics: Adult; Child; Humans; Antitubercular Agents; Arylamine N-Acetyltransferase; Chemical and Drug Induced Liver Injury; Genotype; Isoniazid; Polymorphism, Genetic; Tuberculosis
PubMed: 38629592
DOI: 10.1111/cts.13795 -
Wiley Interdisciplinary Reviews.... 2024Nanocrystals refer to materials with at least one dimension smaller than 100 nm, composing of atoms arranged in single crystals or polycrystals. Nanocrystals have... (Review)
Review
Nanocrystals refer to materials with at least one dimension smaller than 100 nm, composing of atoms arranged in single crystals or polycrystals. Nanocrystals have significant research value as they offer unique advantages over conventional pharmaceutical formulations, such as high bioavailability, enhanced targeting selectivity and controlled release ability and are therefore suitable for the delivery of a wide range of drugs such as insoluble drugs, antitumor drugs and genetic drugs with broad application prospects. In recent years, research on nanocrystals has been progressively refined and new products have been launched or entered the clinical phase of studies. However, issues such as safety and stability still stand that need to be addressed for further development of nanocrystal formulations, and significant gaps do exist in research in various fields in this pharmaceutical arena. This paper presents a systematic overview of the advanced development of nanocrystals, ranging from the preparation approaches of nanocrystals with which the bioavailability of poorly water-soluble drugs is improved, critical properties of nanocrystals and associated characterization techniques, the recent development of nanocrystals with different administration routes, the advantages and associated limitations of nanocrystal formulations, the mechanisms of physical instability, and the enhanced dissolution performance, to the future perspectives, with a final view to shed more light on the future development of nanocrystals as a means of optimizing the bioavailability of drug candidates. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.
Topics: Antineoplastic Agents; Biological Availability; Nanoparticles; Pharmaceutical Preparations; Solubility
PubMed: 38629192
DOI: 10.1002/wnan.1958