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JAMA Network Open Oct 2020Several antifungal drugs are available for antifungal prophylaxis in patients with hematological disease or who are undergoing hematopoietic stem cell transplantation... (Comparative Study)
Comparative Study Meta-Analysis
Comparison of Antifungal Prophylaxis Drugs in Patients With Hematological Disease or Undergoing Hematopoietic Stem Cell Transplantation: A Systematic Review and Network Meta-analysis.
IMPORTANCE
Several antifungal drugs are available for antifungal prophylaxis in patients with hematological disease or who are undergoing hematopoietic stem cell transplantation (HSCT).
OBJECTIVE
To summarize the evidence on the efficacy and adverse effects of antifungal agents using an integrated comparison.
DATA SOURCES
Medline, EMBASE, and the Cochrane Central Register of Controlled Clinical Trials were searched to collect all relevant evidence published in randomized clinical trials that assessed antifungal prophylaxis in patients with hematological disease. Sources were search from inception up to October 2019.
STUDY SELECTION
Studies that compared any antifungal agent with a placebo, no antifungal agent, or another antifungal agent among patients with hematological disease or undergoing HSCT were included. Of 39 709 studies identified, 69 met the criteria for inclusion.
DATA EXTRACTION AND SYNTHESIS
The outcome from each study was estimated using the relative risk (RR) with 95% CIs. The Mantel-Haenszel random-effects model was used. The reliability and validity of the networks were estimated by addressing inconsistencies in the evidence from comparative studies of different treatments. Data were analyzed from December 2019 to February 2020. Reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses for Network Meta-analysis (PRISMA-NMA) guideline.
MAIN OUTCOMES AND MEASURES
The primary outcomes were invasive fungal infections (IFIs) and mortality. The secondary outcomes were fungal infections, proven IFIs, invasive candidiasis, invasive aspergillosis, fungi-related death, and withdrawal owing to adverse effects of the drug.
RESULTS
We identified 69 randomized clinical trials that reported comparisons of 12 treatments with at total of 14 789 patients. Posaconazole was the treatment associated with the best probability of success against IFIs (surface under the cumulative ranking curve, 86.7%; mean rank, 2.5). Posaconazole treatment was associated with a significant reduction in IFIs (RR, 0.57; 95% CI, 0.42-0.79) and invasive aspergillosis (RR, 0.36; 95% CI, 0.15-0.85) compared with placebo. Voriconazole was associated with a significant reduction in invasive candidiasis (RR, 0.15; 95% CI, 0.09-0.26) compared with placebo. However, posaconazole was associated with a higher incidence of withdrawal because of the adverse effects of the drug (surface under the cumulative ranking curve, 17.5%; mean rank, 9.2). In subgroup analyses considering efficacy and tolerance, voriconazole might be the best choice for patients undergoing HSCT, especially allogenic HSCT; however, posaconazole was ranked as the best choice for patients with acute myeloid leukemia or myelodysplastic syndrome.
CONCLUSIONS AND RELEVANCE
These findings suggest that voriconazole may be the best prophylaxis option for patients undergoing HSCT, and posaconazole may be the best prophylaxis option for patients with acute myeloid leukemia or myelodysplastic syndrome.
Topics: Adult; Aged; Aged, 80 and over; Antifungal Agents; Female; Hematologic Diseases; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Mycoses; Pre-Exposure Prophylaxis; Triazoles; Voriconazole
PubMed: 33030550
DOI: 10.1001/jamanetworkopen.2020.17652 -
Asian Pacific Journal of Cancer... Apr 2022we aim to conduct a systematic review and meta-analysis in population of adult MDS patients to elucidate the role of these genes in AML transformation risk. (Meta-Analysis)
Meta-Analysis
Association of Somatic Gene Mutations with Risk of Transformation into Acute Myeloid Leukemia in Patients with Myelodysplastic Syndrome: A Systematic Review and Meta-Analysis.
OBJECTIVES
we aim to conduct a systematic review and meta-analysis in population of adult MDS patients to elucidate the role of these genes in AML transformation risk.
MATERIALS AND METHODS
The protocol for this systematic review and meta-analysis was registered in the international prospective register of systematic reviews (PROSPERO) with ID number of CRD42020218581. Systematic literature search was conducted by all authors up to October 2021 on: (1) PubMed, (2) EBSCOhost, (3) Scopus, (4) JSTOR, and (5) grey literatures. Hand-searching for relevant articles was also conducted. The following keywords with their synonyms and combinations using Boolean operators were applied to all database: "myelodysplastic syndrome", SRSF2", "SF3B1", "U2AF1", "ASXL1", "DNMT3A", "TET2", "IDH1", "IDH2", "RUNX1", "acute myeloid leukemia progression", and "leukemia free survival". Outcome was measured using hazard ratio (HR).
RESULTS
We identified 14 articles to be used for this systematic review and meta-analysis. There was no statistically significant difference in AML transformation risk between U2AF1 mutant and U2AF1 wildtype MDS patients (HR: 1.41; 95% CI: 0.95-2.07, p=0.08, I2=0%). Pooled HR showed that patients with SRSF2 mutation had higher risk of AML transformation (HR 2.62; 95% CI: 1.54-4.45; p= .0004; I2= 55%). The pooled HR for SF3B1 was 0.48 (95% CI: 0.22-1.06, p=0.07, I2=55%). Mutations of TET2, ASXL1, and EZH2 were not associated with AML transformation. Meanwhile, DNMT3A mutations were associated with AML transformation with pooled HR of 2.73 (95% CI: 1.43-5.21; p= 0.08; I2: 67%). The pooled HR for IDH genes was smaller (HR: 2.92; 95%CI: 1.21-7.06; p=0.02; I2:65%). Patients with RUNX1 mutation were associated with AML transformation (HR: 1.85; 95%CI: 1.11-3.09; p=0.02; I2:38%).
CONCLUSION
Based from our analyses, MDS patients with mutations of SRSF2, DNMT3A, IDH, and RUNX1 have higher hazard ratio for AML transformation.
Topics: Adult; Core Binding Factor Alpha 2 Subunit; Humans; Leukemia, Myeloid, Acute; Mutation; Myelodysplastic Syndromes; Splicing Factor U2AF
PubMed: 35485665
DOI: 10.31557/APJCP.2022.23.4.1107 -
Blood Advances Jun 2019The terminology applied to autoimmune hemolytic anemia (AIHA) seems inconsistent. We aimed to evaluate the consistency of definitions used for diagnosis and treatment.... (Comparative Study)
Comparative Study
The terminology applied to autoimmune hemolytic anemia (AIHA) seems inconsistent. We aimed to evaluate the consistency of definitions used for diagnosis and treatment. In this systematic review of literature from January 2006 to December 2015, we assessed heterogeneity in the definition of AIHA and its subtypes, refractory disease, disease phase, severity, criteria for treatment response, and response durability. A Medline search for anemia, hemolytic, autoimmune was supplemented with keyword searches. Main exclusions were conference abstracts, animal and non-English studies, and studies with <10 cases. Of 1371 articles retrieved, 1209 were excluded based on titles and abstracts. Two authors independently reviewed 10% and 16% of abstracts and full papers, respectively. After full-paper review, 84 studies were included. AIHA was most frequently (32 [52%] of 61) defined as hemolytic anemia with positive direct antiglobulin test (DAT) and exclusion of alternatives, but 10 of 32 also recognized DAT-negative AIHA. A lower threshold for diagnosis of DAT-negative AIHA was observed in literature on chronic lymphocytic leukemia. Definitions of anemia, hemolysis, and exclusion criteria showed substantial variation. Definitions of primary/secondary cold agglutinin disease/syndrome were not consistent. Forty-three studies provided criteria for treatment response, and other than studies from 1 center, these were almost entirely unique. Other criteria were rarely defined. Only 7, 0, 3, 2, 2, and 3 studies offered definitions of warm AIHA, paroxysmal cold hemoglobinuria, mixed AIHA, AIHA severity, disease phase, and refractory AIHA, respectively. Marked heterogeneity in the time period sampled indicates the need to standardize AIHA terminology.
Topics: Anemia, Hemolytic, Autoimmune; Coombs Test; Erythrocytes; Hemoglobinuria, Paroxysmal; Hemolysis; Humans; Immunoglobulin G; Publications; Severity of Illness Index; Terminology as Topic
PubMed: 31235526
DOI: 10.1182/bloodadvances.2019000036 -
British Journal of Haematology Jan 2019Many patients with lower-risk myelodysplastic syndrome (MDS) experience anaemia, which has negative consequences. Erythropoiesis-stimulating agents (ESAs) and their... (Review)
Review
Clinical effectiveness and safety of erythropoietin-stimulating agents for the treatment of low- and intermediate-1-risk myelodysplastic syndrome: a systematic literature review.
Many patients with lower-risk myelodysplastic syndrome (MDS) experience anaemia, which has negative consequences. Erythropoiesis-stimulating agents (ESAs) and their biosimilars are used to treat anaemia in MDS and, currently, epoetin alfa and darbepoetin alfa are commonly used and recommended by clinical guidelines. To better understand the evidence available on the use of ESAs for anaemia in lower-risk MDS, we conducted a systematic literature review to identify randomized and nonrandomized prospective studies reporting on clinical efficacy/effectiveness, patient-reported quality of life (QoL), and safety. We extended our review to include retrospective studies for darbepoetin alfa specifically and to ascertain the feasibility of completing an indirect network meta-analysis comparing epoetin and darbepoetin alfa. Overall, 53 articles reporting on 35 studies were included. The studies indicated a clinical benefit of ESAs, with benefits observed across key clinical outcomes. ESAs showed consistent improvement in erythroid response rates (ESA-naïve, 45-73%; previous ESA exposure, 25-75%) and duration of response. Comparative studies demonstrated similar progression to acute myeloid leukaemia and several showed improved overall survival and QoL. Limited safety concerns were identified. This analysis confirmed ESA therapy should be the foremost first-line treatment of anaemia in most patients with lower-risk MDS who lack the 5q deletion.
Topics: Biosimilar Pharmaceuticals; Darbepoetin alfa; Epoetin Alfa; Hematinics; Humans; Myelodysplastic Syndromes; Prospective Studies; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 30549002
DOI: 10.1111/bjh.15707 -
Clinical Lymphoma, Myeloma & Leukemia Feb 2023The global incidence of myelodysplastic syndromes (MDS) has been estimated as 0.06 to 0.26/100,000. Since their introduction, hypomethylating agents have played a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The global incidence of myelodysplastic syndromes (MDS) has been estimated as 0.06 to 0.26/100,000. Since their introduction, hypomethylating agents have played a central role in the treatment of MDS, with heterogeneous real-world outcomes.
MATERIALS AND METHODS
We assessed and synthesized clinical outcomes of azacitidine (AZA) monotherapy in treatment-naïve patients with higher-risk MDS. A systematic literature review was conducted by searching MEDLINE, Embase, and CENTRAL to identify randomized clinical trials (RCTs) and observational studies, both prospective and retrospective, reporting complete remission (CR), partial remission (PR), overall survival (OS), duration of response (DOR), time-to-response (TTR), and myelosuppressive adverse events (AEs) for patients treated with AZA monotherapy. Noncomparative meta-analyses were used to summarize effects.
RESULTS
The search identified 3250 abstracts, of which 34 publications describing 16 studies (5 RCTs, 3 prospective, and 8 retrospective observational) were included. Across all studies, pooled CR was 16%; PR was 6%; Median OS was 16.4 months; median DOR was 10.1 months; median TTR was 4.6 months. Proportions of grade 3/4 anemia and thrombocytopenia AEs were 10% and 30%.
CONCLUSIONS
The effectiveness and efficacy of AZA monotherapy-as measured by CR and median OS-was limited. These findings highlight a significant unmet medical need for effective treatments for patients with higher-risk MDS.
Topics: Humans; Azacitidine; Antimetabolites, Antineoplastic; Myelodysplastic Syndromes; Treatment Outcome; Remission Induction
PubMed: 36428152
DOI: 10.1016/j.clml.2022.11.002 -
Journal of Cancer Research and Clinical... Sep 2017A systematic review and meta-analysis were performed to explore the efficacy and safety of allogeneic hematopoietic stem cell transplantation with a reduced intensity... (Meta-Analysis)
Meta-Analysis Review
Reduced intensity conditioning of allogeneic hematopoietic stem cell transplantation for myelodysplastic syndrome and acute myeloid leukemia in patients older than 50 years of age: a systematic review and meta-analysis.
PURPOSE
A systematic review and meta-analysis were performed to explore the efficacy and safety of allogeneic hematopoietic stem cell transplantation with a reduced intensity conditioning regimen in elderly patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
METHODS
Overall survival (OS) and event-free survival (EFS) were established as the primary endpoints for directly assessing the efficacy, and non-relapse mortality (NRM) for safety. The eligible patients were at or above 50 years of age, and the outcomes of the typical elderly patients (≥60 years) were analyzed individually.
RESULTS
The pooled estimates (95% confidence interval (CI)) for 1-year OS, EFS and NRM were 65 (55-74) %, 50 (44-55) % and 26 (21-30) %, respectively; as for the patients ≥60 years of age, these were 63 (53-72) %, 46 (41-50) % and 28 (23-32) %, respectively. No significantly statistical difference achieved between MDS and AML patients in 1-year EFS and NRM [relative risk (RR) 0.91, 95% CI 0.80-1.04; P = 0.172 and RR 1.18, 95% CI 0.82-1.69; P = 0.365]. The patients with lower diseases risk had the possibility of higher OS rate at ≥ 3 years than those with higher diseases risk (RR 1.37, 95% CI 0.95-1.97; P = 0.088). The patients had significantly higher 2-year OS and EFS rates in complete remission (CR, CR1 and CR2) at transplantation compared to those with advanced diseases (P < 0.05).
CONCLUSIONS
RIC-alloHSCT is a feasible treatment option for the patients older than 50 year of age with MDS and AML. Advanced diseases status and higher diseases risk may be the poor factors for prognosis.
Topics: Aged; Aged, 80 and over; Female; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Myelodysplastic Syndromes; Transplantation Conditioning; Transplantation, Homologous
PubMed: 28470473
DOI: 10.1007/s00432-017-2429-z -
Clinical and Experimental Rheumatology 2015A number of patients with Behçet's disease (BD) associated with myelodysplastic syndrome (MDS) with or without trisomy 8 have been reported. A high frequency of... (Review)
Review
OBJECTIVES
A number of patients with Behçet's disease (BD) associated with myelodysplastic syndrome (MDS) with or without trisomy 8 have been reported. A high frequency of gastrointestinal (GI) involvement was reported in such patients. The aim of this systematic literature review was to delineate whether GI involvement is an inherent feature of BD associated with MDS, whether these patients do actually have BD rather than GI symptoms related to MDS, and whether the presence of trisomy 8 plays a role in the disease expression of BD associated with MDS.
METHODS
A systematic literature review was performed in PubMed using the keywords (Behçet's disease OR Behçet's syndrome) AND (myelodysplastic syndrome OR trisomy 8) until December 2013.
RESULTS
Data from 39 manuscripts that met the inclusion criteria, reporting on 52 patients were analysed. GI involvement was common in reports from both the Far East and non-Far East countries (75% vs. 50.0%, p=0.15). These patients had typical BD manifestations, except for 1 patient who had only oral ulcers and gastrointestinal involvement. The presence of trisomy 8 seems to be associated with an increased frequency of fever (79.5% vs. 33.3%, p=0.005).
CONCLUSIONS
GI involvement seems to be an inherent feature of BD associated with MDS regardless of geographic differences. Despite the increased frequency of GI involvement in these patients, MDS does not seem to modify the clinical expression of gastrointestinal involvement. Presence of trisomy 8 seems to modify the disease expression with an increased frequency of fever.
Topics: Behcet Syndrome; Chromosomes, Human, Pair 8; Gastrointestinal Diseases; Genetic Predisposition to Disease; Humans; Myelodysplastic Syndromes; Phenotype; Prognosis; Risk Factors; Trisomy
PubMed: 25664843
DOI: No ID Found -
Frontiers in Pharmacology 2021The hypomethylating agents (HMAs) azacitidine (AZA) and decitabine (DAC) have been widely used in patients with acute myeloid leukemia (AML) and higher-risk...
Comparison Between Decitabine and Azacitidine for Patients With Acute Myeloid Leukemia and Higher-Risk Myelodysplastic Syndrome: A Systematic Review and Network Meta-Analysis.
The hypomethylating agents (HMAs) azacitidine (AZA) and decitabine (DAC) have been widely used in patients with acute myeloid leukemia (AML) and higher-risk myelodysplastic syndrome (HR-MDS). However, few direct clinical trials have been carried out to compare the efficacy and adverse events (AEs) between these two agents. The clinical choice between them is controversial. A systematic review and network meta-analysis (NMA) was performed to compare the efficacy, safety, and survival of DAC and AZA in AML and HR-MDS patients. We systematically searched MEDLINE, Embase, Web of Science, and Cochrane Library through March 15, 2021. Randomized controlled trials (RCTs) on AML or HR-MDS patients comparing the efficacy and safety between DAC and AZA or comparing one of HMAs to conventional care regimens (CCR) were selected. Eight RCTs ( = 2,184) were identified in the NMA. Four trials compared AZA to CCR, and four compared DAC to CCR. Direct comparisons indicated that, compared to CCR, both AZA and DAC were associated with higher overall response (OR) rate (AZA vs. CCR: relative risk (RR) = 1.48, 95% CI 1.05-2.1; DAC vs. CCR: RR = 2.14, 95% CI 1.21-3.79) and longer overall survival (OS) (AZA vs. CCR: HR = 0.64, 95% CI 0.50-0.82; DAC vs. CCR: HR = 0.84, 95% CI 0.72-0.98), and AZA showed higher rate of complete remission with incomplete blood count recovery (CRi) (HR = 2.52, 95% CI 1.27-5). For the indirect method, DAC showed a higher complete remission (CR) rate than AZA in patients with both AML (RR = 2.28, 95% CI 1.12-4.65) and MDS (RR = 7.57, 95% CI 1.26-45.54). Additionally, DAC significantly increased the risk of 3/4 grade anemia (RR = 1.61, 95% CI: 1.03-2.51), febrile neutropenia (RR = 4.03, 95% CI: 1.41-11.52), and leukopenia (RR = 3.43, 95% CI 1.64-7.16) compared with AZA. No statistical significance was found for the other studied outcomes. Compared to CCR, both AZA and DAC can promote outcomes in patients with AML and HR-MDS. DAC showed higher efficacy especially CR rate than AZA (low-certainty evidence), while AZA experienced lower frequent grade 3/4 cytopenia than patients receiving DAC treatment.
PubMed: 34483903
DOI: 10.3389/fphar.2021.701690 -
Transplantation and Cellular Therapy Dec 2021Disease relapse remains the major cause of death among patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) who receive an allogeneic... (Meta-Analysis)
Meta-Analysis
Hypomethylating Agents and FLT3 Inhibitors As Maintenance Treatment for Acute Myeloid Leukemia and Myelodysplastic Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation-A Systematic Review and Meta-Analysis.
BACKGROUND
Disease relapse remains the major cause of death among patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) who receive an allogeneic hematopoietic cell transplant (allo-HCT). Maintenance treatment with FLT3 inhibitors and hypomethylating agents (HMA) has been studied in various clinical trials with mixed results.
OBJECTIVE
To synthesize the current evidence on the efficacy and safety of FLT3 inhibitors and HMA for maintenance therapy after allo-HCT in AML and MDS.
METHODS
For this systematic review and meta-analysis Cochrane Library, Google Scholar, Ovid Medline, Ovid Embase, PubMed, Scopus, and Web of Science Core Collection were searched from inception to March 2021 for studies on maintenance therapies after allo-HCT in AML and MDS. Studies were excluded if they were reviews, commentaries, case series with <5 patients, or basic research articles, not published in English, not on post-allo-HCT maintenance with FLT3 inhibitors or HMA in AML or MDS, or if they were clinical trials without published results or duplicate publications from the same patient cohort. Studies with insufficient reporting of the primary endpoint (2-year overall survival [OS]) and studies using FLT3 inhibitors or HMA for pre-emptive treatment of imminent relapse based on positive measurable residual disease testing were excluded. Random-effects models were used to pool response rates for the primary outcome of 2-year OS. Hazard ratios (HR) for death and relapse were calculated for studies that included a control group. Rates of relapse-free survival (RFS), non-relapse mortality, and acute and chronic graft-versus-host-disease (GVHD) were studied as secondary endpoints. Downs and Black checklist and risk of bias assessments were used to gauge the quality of individual studies. The study protocol has been registered on PROSPERO (CRD42020187298).
RESULTS
Our search strategy identified 5559 studies. Twenty-one studies with a total of 809 patients were included in the meta-analysis. The 2-year OS rates were 81.7% (95% confidence interval [CI], 73.8%-87.7%) and 65.7% (95% CI, 55.1%-74.9%) among patients treated with FLT3 inhibitors and HMA, respectively. In sensitivity analyses restricted to studies that included a control group, maintenance therapy with FLT3 inhibitors (HR for death = 0.41; 95% CI, 0.26-0.62) or HMA (HR = 0.45; 95% CI, 0.31-0.66) appeared superior to no maintenance therapy. The 2-year RFS rates were 79.8% (95% CI, 75.0%-83.9%) and 62.4% (95% CI, 50.6%-72.9%) among patients treated with FLT3 inhibitors and HMA, respectively. Rates of any grade acute and chronic GVHD were 33.1% (95% CI, 25.4%-41.8%; grade 3/4: 16.5%) and 42.5% (95% CI, 26.3%-60.4%) among FLT3 inhibitor and 42.7% (95% CI, 33.5%-52.4%; grade 3/4: 8.1%) and 41.5% (95% CI, 32.0%-51.6%) among HMA-treated patients, respectively.
CONCLUSION
Maintenance therapy with either FLT3 inhibitors or HMA after allo-HCT can lead to prolonged and improved OS and RFS with a favorable safety profile. Additional studies are needed to define the optimal duration of treatment, the role of measurable residual disease status, and transplant characteristics in patient selection.
Topics: Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Protein Kinase Inhibitors; fms-Like Tyrosine Kinase 3
PubMed: 34551341
DOI: 10.1016/j.jtct.2021.09.005 -
Frontiers in Medicine 2022Hypomethylating agents (HMAs) seem to have a range of properties favorable to post-allogeneic hematopoietic stem cell transplantation (allo-SCT) maintenance in acute...
Maintenance With Hypomethylating Agents After Allogeneic Stem Cell Transplantation in Acute Myeloid Leukemia and Myelodysplastic Syndrome: A Systematic Review and Meta-Analysis.
INTRODUCTION
Hypomethylating agents (HMAs) seem to have a range of properties favorable to post-allogeneic hematopoietic stem cell transplantation (allo-SCT) maintenance in acute myeloid leukemia (AML) patients.
MATERIALS AND METHODS
The Embase, MEDLINE, and Cochrane Central Register of Controlled Trials databases were independently searched by two investigators to identify relevant studies published inception to 18 November 2021. These trials compared HMA maintenance to observation following allo-SCT for AML or myelodysplastic syndrome.
RESULTS
The meta-analysis eligibility criteria were fulfilled by 14 studies. The overall survival and relapse-free survival of the HMA maintenance group were superior to the observation group, with a pooled risk ratio (RR) of 1.38 and 1.46, respectively. Moreover, the cumulative incidence of relapse was significantly lower in those who received HMAs. The HMA group also had lower non-relapse mortality compared with the observation group. Overall, the incidences of grades III-IV acute graft-vs.-host disease (GVHD) and chronic GVHD did not differ in both groups. However, when looking specifically at those receiving decitabine maintenance, the rate of chronic GVHD seemed to be lower compared with observation alone.
CONCLUSIONS
The current systematic review and meta-analysis illustrated that AML and MDS patients receiving HMA maintenance after allo-SCT had better outcomes in regards to OS, RFS, NRM, CIR as well as a reduced incidence of chronic GVHD.
PubMed: 35242779
DOI: 10.3389/fmed.2022.801632