-
Leukemia Research Jun 2024Acute myeloid leukemia (AML) is a complex disease with diverse mutations, including prevalent mutations in the FMS-like receptor tyrosine kinase 3 (FLT3) gene that lead... (Review)
Review
BACKGROUND
Acute myeloid leukemia (AML) is a complex disease with diverse mutations, including prevalent mutations in the FMS-like receptor tyrosine kinase 3 (FLT3) gene that lead to poor prognosis. Recent advancements have introduced FLT3 inhibitors that have improved outcomes for FLT3-mutated AML patients, however, questions remain on their application in complex conditions such as relapsed/refractory (R/R) disease. Therefore, we aimed to evaluate the clinical effectiveness of second-generation FLT3 inhibitors in treating patients with R/R AML.
METHODS
A systematic literature search of PubMed, MEDLINE, SCOPUS and Google Scholar databases was made to identify relevant studies up to January 30, 2024. This study was conducted following the guidelines of the PRISMA.
RESULTS
The ADMIRAL trial revealed significantly improved overall survival and complete remission rates with gilteritinib compared to salvage chemotherapy, with manageable adverse effects. Ongoing research explores its potential in combination therapies, showing synergistic effects with venetoclax and promising outcomes in various clinical trials. The QuANTUM-R trial suggested longer overall survival with quizartinib compared to standard chemotherapy, although concerns were raised regarding trial design and cardiotoxicity. Ongoing research explores combination therapies involving quizartinib, such as doublet or triplet regimens with venetoclax, showing promising outcomes in FLT3-mutated AML patients.
CONCLUSION
These targeted therapies offer promise for managing this subgroup of AML patients, but further research is needed to optimize their use. This study underscores the importance of personalized treatment based on genetic mutations in AML, paving the way for more effective and tailored approaches to combat the disease.
Topics: Humans; fms-Like Tyrosine Kinase 3; Leukemia, Myeloid, Acute; Protein Kinase Inhibitors; Drug Resistance, Neoplasm; Mutation; Aniline Compounds; Phenylurea Compounds; Neoplasm Recurrence, Local; Pyrazines; Benzothiazoles
PubMed: 38692232
DOI: 10.1016/j.leukres.2024.107505 -
Headache Apr 2024To assess the comparative effectiveness and safety of parenteral agents for pain reduction in patients with acute migraine. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To assess the comparative effectiveness and safety of parenteral agents for pain reduction in patients with acute migraine.
BACKGROUND
Parenteral agents have been shown to be effective in treating acute migraine pain; however, the comparative effectiveness of different approaches is unclear.
METHODS
Nine electronic databases and gray literature sources were searched to identify randomized clinical trials assessing parenteral agents to treat acute migraine pain in emergency settings. Two independent reviewers completed study screening, data extraction, and Cochrane risk-of-bias assessment, with differences being resolved by adjudication. The protocol of the review was registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42018100096).
RESULTS
A total of 97 unique studies were included, with most studies reporting a high or unclear risk of bias. Monotherapy, as well as combination therapy, successfully reduced pain scores prior to discharge. They also increased the proportion of patients reporting pain relief and being pain free. Across the pain outcomes assessed, combination therapy was one of the higher ranked approaches and provided robust improvements in pain outcomes, including lowering pain scores (mean difference -3.36, 95% confidence interval [CI] -4.64 to -2.08) and increasing the proportion of patients reporting pain relief (risk ratio [RR] 2.83, 95% CI 1.74-4.61). Neuroleptics and metoclopramide also ranked high in terms of the proportion of patients reporting pain relief (neuroleptics RR 2.76, 95% CI 2.12-3.60; metoclopramide RR 2.58, 95% CI 1.90-3.49) and being pain free before emergency department discharge (neuroleptics RR 4.8, 95% CI 3.61-6.49; metoclopramide RR 4.1, 95% CI 3.02-5.44). Most parenteral agents were associated with increased adverse events, particularly combination therapy and neuroleptics.
CONCLUSIONS
Various parenteral agents were found to provide effective pain relief. Considering the consistent improvements across various outcomes, combination therapy, as well as monotherapy of either metoclopramide or neuroleptics are recommended as first-line options for managing acute migraine pain. There are risks of adverse events, especially akathisia, following treatment with these agents. We recommend that a shared decision-making model be considered to effectively identify the best treatment option based on the patient's needs.
Topics: Humans; Analgesics; Emergency Service, Hospital; Metoclopramide; Migraine Disorders; Network Meta-Analysis; Pain Management; Randomized Controlled Trials as Topic
PubMed: 38644702
DOI: 10.1111/head.14704 -
Open Veterinary Journal Jan 2024Antimicrobial resistance (AMR) is recognized globally as a significant health challenge, but its extent remains unclear in many regions. It is crucial to prioritize a...
BACKGROUND
Antimicrobial resistance (AMR) is recognized globally as a significant health challenge, but its extent remains unclear in many regions. It is crucial to prioritize a foundational evaluation of AMR prevalence to facilitate the implementation of laboratory-based surveillance. Adopting a One Health perspective, this study outlines the present AMR status in the Middle East.
AIM
To synthesize the current state of knowledge on AMR in the Middle East, delineate the contributions of different sectors (human health, animal health, and environment), and discern the effectiveness of One Health interventions in mitigating AMR.
METHODS
An exhaustive literature search was conducted via PubMed, ScienceDirect, and Google Scholar. Potential articles were screened and assessed for eligibility based on prescribed eligibility criteria. Data synthesis was done, and the results were reported and discussed thematically.
RESULTS
Twenty-three studies were included in the study and published between 2019 and 2023. Most studies reveal substantial challenges in treating infections, with a significant prevalence of resistance in critical care units, particularly against extended-spectrum beta-lactamases and carbapenem-resistant Gram-negative bacteria. Colistin and imipenem resistance in pediatric populations further emphasize the urgency of understanding and addressing diverse resistance mechanisms in the region. Studies on urinary pathogens, bacteremia, and biofilm formation highlight the multifaceted challenge of AMR. The emergence of resistance to key antibiotics emphasizes the urgency for tailored treatment strategies.
CONCLUSION
Given the interconnectedness of human, animal, and environmental health, a One Health perspective is imperative. The diverse challenge demands coordinated efforts, including innovative interventions and public health policies. Bridging existing gaps through future research is crucial for evidence-based and context-specific strategies in combating AMR in the region.
Topics: Humans; Animals; Anti-Bacterial Agents; Drug Resistance, Bacterial; One Health; Carbapenems; Bacteria; Middle East
PubMed: 38633186
DOI: 10.5455/OVJ.2024.v14.i1.53 -
Systematic Reviews Apr 2024Leptospirosis, an important zoonotic bacterial disease, commonly affects resource-poor populations and results in significant morbidity and mortality worldwide. The... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Leptospirosis, an important zoonotic bacterial disease, commonly affects resource-poor populations and results in significant morbidity and mortality worldwide. The value of antibiotics in leptospirosis remains unclear, as evidenced by the conflicting opinions published.
METHODS
We conducted a search in the PubMed, Web of Science, and Cochrane Library databases for studies. These studies included clinical trials and retrospective studies that evaluated the efficacy or safety of antibiotics for leptospirosis treatment. The primary outcomes assessed were defervescence time, mortality rate, and hospital stays. Subgroup analyses were performed based on whether there were cases involving children and whether there were cases of severe jaundice. Safety was defined as the prevalence of adverse events associated with the use of antibiotics. p scores were utilized to rank the efficacy of the antibiotics.
RESULTS
There are included 9 randomized controlled trials (RCTs), 1 control trial (CT), and 3 retrospective studies (RS) involving 920 patients and 8 antibiotics. Six antibiotics resulted in significantly shorter defervescence times compared to the control, namely cefotaxime (MD, - 1.88; 95% CI = - 2.60 to - 1.15), azithromycin (MD, - 1.74; 95% CI = - 2.52 to - 0.95), doxycycline (MD, - 1.53; 95% CI = - 2.05 to - 1.00), ceftriaxone (MD, - 1.22; 95% CI = - 1.89 to - 0.55), penicillin (MD, - 1.22; 95% CI = - 1.80 to - 0.64), and penicillin or ampicillin (MD, - 0.08; 95% CI = - 1.01 to - 0.59). The antibiotics were not effective in reducing the mortality and hospital stays. Common adverse reactions to antibiotics included Jarisch-Herxheimer reaction, rash, headache, and digestive reactions (nausea, vomiting, diarrhea, abdominal pain, and others).
CONCLUSIONS
Findings recommend that leptospirosis patients be treated with antibiotics, which significantly reduced the leptospirosis defervescence time. Cephalosporins, doxycycline, and penicillin are suggested, and azithromycin may be a suitable alternative for drug-resistant cases.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42022354938.
Topics: Humans; Anti-Bacterial Agents; Azithromycin; Doxycycline; Leptospirosis; Network Meta-Analysis; Penicillins
PubMed: 38627798
DOI: 10.1186/s13643-024-02519-y -
Critical Care (London, England) Apr 2024To perform a systematic review with meta-analysis with the dual intent of assessing the impact of attaining aggressive vs. conservative beta-lactams PK/PD target on the... (Meta-Analysis)
Meta-Analysis
Impact of attaining aggressive vs. conservative PK/PD target on the clinical efficacy of beta-lactams for the treatment of Gram-negative infections in the critically ill patients: a systematic review and meta-analysis.
BACKGROUND
To perform a systematic review with meta-analysis with the dual intent of assessing the impact of attaining aggressive vs. conservative beta-lactams PK/PD target on the clinical efficacy for treating Gram-negative infections in critical patients, and of identifying predictive factors of failure in attaining aggressive PK/PD targets.
METHODS
Two authors independently searched PubMed-MEDLINE and Scopus database from inception to 23rd December 2023, to retrieve studies comparing the impact of attaining aggressive vs. conservative PK/PD targets on clinical efficacy of beta-lactams. Independent predictive factors of failure in attaining aggressive PK/PD targets were also assessed. Aggressive PK/PD target was considered a100%fT, and clinical cure rate was selected as primary outcome. Meta-analysis was performed by pooling odds ratios (ORs) extrapolated from studies providing adjustment for confounders using a random-effects model with inverse variance method.
RESULTS
A total of 20,364 articles were screened, and 21 observational studies were included in the meta-analysis (N = 4833; 2193 aggressive vs. 2640 conservative PK/PD target). Attaining aggressive PK/PD target was significantly associated with higher clinical cure rate (OR 1.69; 95% CI 1.15-2.49) and lower risk of beta-lactam resistance development (OR 0.06; 95% CI 0.01-0.29). Male gender, body mass index > 30 kg/m, augmented renal clearance and MIC above the clinical breakpoint emerged as significant independent predictors of failure in attaining aggressive PK/PD targets, whereas prolonged/continuous infusion administration of beta-lactams resulted as protective factor. The risk of bias was moderate in 19 studies and severe in the other 2.
CONCLUSIONS
Attaining aggressive beta-lactams PK/PD targets provided significant clinical benefits in critical patients. Our analysis could be useful to stratify patients at high-risk of failure in attaining aggressive PK/PD targets.
Topics: Humans; Male; beta-Lactams; Anti-Bacterial Agents; Critical Illness; Treatment Outcome; Infusions, Intravenous
PubMed: 38627763
DOI: 10.1186/s13054-024-04911-5 -
Immunopharmacology and Immunotoxicology Jun 2024The purpose of this study was to investigate the efficacy and safety of lenvatinib in various types of solid tumors. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The purpose of this study was to investigate the efficacy and safety of lenvatinib in various types of solid tumors.
METHOD
By searching PubMed, Web of Science, Cochrane, CNKI, Wanfang and other databases, all the literatures about the comparison of clinical efficacy of lenvatinib in the treatment of various solid tumors. According to the criteria of inclusion and exclusion of literature, two participants screened the literature, collated the data and evaluated the literature. RevMan 5.4 software was used for meta-analysis of the included literatures.
RESULTS
A total of 12 studies were included, including 5213 patients. Meta-analysis showed that, in terms of efficacy, the risk (HR) of prolonging PFS in the treatment of various solid tumors in the lenvatinib group was 1.91 times that in the control group (HR = 1.91, 95% CI: 1.58-2.31, < 0.00001), and the risk (HR) of prolonging OS was 1.27 times that in the single targeted drug group (HR = 1.27, 95% CI: 1.15-1.40, < 0.00001). In terms of safety, the risk of adverse events in the treatment of various solid tumors in the lenvatinib group was higher than that in the control group, especially in Endocrine Toxicities, Renal/Urinary Toxicities, Vascular Toxicities, Musculoskeletal/a Connective Tissue Toxicities and Metabolism/Nutrition Toxicities.
CONCLUSIONS
Lenvatinib in various solid tumors can prolong OS and disease PFS of patients, improve the clinical benefit rate and improve the quality of life of patients. At the same time, there is a certain incidence of adverse events, and symptomatic intervention should be given in clinical medication.
Topics: Humans; Antineoplastic Agents; Neoplasms; Phenylurea Compounds; Protein Kinase Inhibitors; Quinolines; Treatment Outcome
PubMed: 38627024
DOI: 10.1080/08923973.2024.2344153 -
Asian Journal of Andrology Jul 2024This study compared different doublet and triplet therapies for efficacy and safety in metastatic hormone-sensitive prostate cancer (mHSPC). PubMed, EMBASE, and the... (Meta-Analysis)
Meta-Analysis
This study compared different doublet and triplet therapies for efficacy and safety in metastatic hormone-sensitive prostate cancer (mHSPC). PubMed, EMBASE, and the Cochrane Library were comprehensively searched for eligible randomized controlled trials (RCTs) published from inception to October 2023. Interventions included abiraterone, apalutamide, enzalutamide, docetaxel, darolutamide, and androgen deprivation therapy (ADT), either as doublet or triplet therapies. The outcomes examined were overall survival (OS), progression-free survival (PFS), castration-resistant prostate cancer (CRPC)-free survival, time to symptomatic skeletal event (SSE), and toxicity. The surface under the cumulative ranking curve (SUCRA) was determined to identify the preferred treatments. Ten RCTs were included. The combination of darolutamide, docetaxel, and ADT had the highest SUCRA of 84.3 for OS, followed by combined abiraterone, docetaxel, and ADT (SUCRA = 71.6). The highest SUCRAs for PFS were observed for triplet therapies (abiraterone, docetaxel, and ADT [SUCRA = 74.9], followed by enzalutamide, docetaxel, and ADT [SUCRA = 74.3]) and other androgen receptor axis-targeted therapy-based doublet therapies (SUCRAs: 26.5-59.3). Darolutamide, docetaxel, and ADT had the highest SUCRAs, i.e ., 80.8 and 84.0 regarding CRPC-free survival and time to SSE, respectively. Regarding Grade >3 adverse events (AEs), the SUCRAs of triplet therapies (SUCRAs: 14.8-31.5) were similar to that of docetaxel and ADT (SUCRA = 39.5). Three studies had a low risk of bias in all categories; the remaining studies had at least an unclear risk of bias in at least one category. Triplet therapy demonstrated potentially enhanced effectiveness than doublet therapy in mHSPC, with acceptable safety concerns. Darolutamide might be the optimal option for triplet therapy in combination with docetaxel and ADT.
Topics: Male; Humans; Network Meta-Analysis; Docetaxel; Antineoplastic Combined Chemotherapy Protocols; Benzamides; Prostatic Neoplasms; Phenylthiohydantoin; Androstenes; Nitriles; Androgen Antagonists; Prostatic Neoplasms, Castration-Resistant; Thiohydantoins; Randomized Controlled Trials as Topic; Pyrazoles
PubMed: 38624195
DOI: 10.4103/aja20242 -
Diagnostic Microbiology and Infectious... Jul 2024Various bacteria produce complicated infections that are difficult to treat worldwide. Ceftobiprole is effective against resistant Gram-positive and Gram-negative... (Meta-Analysis)
Meta-Analysis
Ceftobiprole mono-therapy versus combination or non-combination regimen of standard antibiotics for the treatment of complicated infections: A systematic review and meta-analysis.
OBJECTIVE
Various bacteria produce complicated infections that are difficult to treat worldwide. Ceftobiprole is effective against resistant Gram-positive and Gram-negative bacteria.
METHODS
This review assessed effectiveness and safety of ceftobiprole monotherapy for severe infections. A systematic review and meta-analysis of randomized controlled trials comparing clinical cure, microbiological cure, and safety of ceftobiprole alone to a combination or non-combination antibiotic regimen was conducted. Until December 20, 2022, we searched a major databases.
RESULTS
This study includes 4168 patients from six trials. Ceftobiprole and comparator-received patients had similar clinical responses for all patient population. Also, the eradication rate of all organisms and specific pathogenic bacteria in microbiologically examined patients was comparable between the groups. Ceftobiprole induced more gastrointestinal side events than comparable drugs, mostly nausea [OR 1.91 (1.26-2.90), p=<0.01]. While skin-related adverse events were significantly associated with comparator antibiotics [6 trials, 4062 patients; OR 0.77 (0.60-0.99), p=0.03].
CONCLUSION
Ceftobiprole monotherapy is effective and safe for severe infections caused by Gram-positive or Gram-negative bacteria.
Topics: Humans; Anti-Bacterial Agents; Cephalosporins; Drug Therapy, Combination; Randomized Controlled Trials as Topic; Bacterial Infections; Treatment Outcome; Gram-Negative Bacteria
PubMed: 38615599
DOI: 10.1016/j.diagmicrobio.2024.116263 -
Journal of Nepal Health Research Council Mar 2024This systematic review aimed to determine the antimicrobial resistance pattern of the extended-spectrum β-lactamases producing Escherichia coli (ESBL-EC) in urine... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This systematic review aimed to determine the antimicrobial resistance pattern of the extended-spectrum β-lactamases producing Escherichia coli (ESBL-EC) in urine samples in Nepal.
METHODS
Systematic literature review was conducted to locate all articles reporting ESBL-EC in urine samples published between January 2012 to December 2022. The Egger's weighted regression analysis was done to assess the publication bias. A random-effects model was used to calculate the pooled prevalence and corresponding 95% confidence interval due to significant between-study heterogeneity. The strength of correlation between multidrug resistance and ESBL production in E.coli strains was determined using Pearson's correlation coefficient. The data were analyzed using R-language 4.2.2. software.
RESULTS
The combined prevalence of E.coli in urine samples was found to be 14 % (95% CI, 11-18), while the overall pooled prevalence of ESBL E.coli and MDR E.coli were 30% (95% CI, 20-42) and 70% (95% CI, 38-90) respectively. A strong positive correlation of 0.99 (95% CI, 0.89-1.0) was found between ESBL production and MDR among E.coli isolates. Imipenem was the drug of choice against ESBL-E.coli in urine specimens.
CONCLUSIONS
Our analyses showed the overall ESBL-EC and MDR-EC burden in Nepal is considerably high. Likewise, the study also infers an increasing trend of antibiotic resistance pattern of ESBL-EC in urine samples.
Topics: Humans; Nepal; Drug Resistance, Microbial; Escherichia coli; Imipenem; Language
PubMed: 38615204
DOI: 10.33314/jnhrc.v21i3.4723 -
Medicine Apr 2024Tyrosine kinase inhibitors (TKIs) have been approved for treating patients with clinically advanced metastatic thyroid cancer. However among the many TKIs, it remains... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Tyrosine kinase inhibitors (TKIs) have been approved for treating patients with clinically advanced metastatic thyroid cancer. However among the many TKIs, it remains unknown which regimen is the best choice for these patients.
METHODS
We conducted a systematic review and network meta-analysis to compare the survival benefits and efficacy of the available first-line regimens. We conducted an active search for phase II, III, or IV randomized controlled trials (RCTs) in the PubMed, Embase, and Cochrane databases to compare the effects of at least 2 drugs in the systemic treatment of advanced or metastatic thyroid cancer up to May 2023. The network meta-analysis model was adjusted using Bayesian Network model. Twelve trials with 2535 patients were included in our meta-analysis. The overall survival (OS), progression-free survival (PFS), and serious adverse events (SAEs) were taken as reference indicators. We also performed subgroup analyses of OS and PFS in medullary thyroid cancer (MTC) and radioiodine-refractory differentiated thyroid cancer (RR-DTC) to explore the variations of TKIs in different groups.
RESULTS
As a result, apatinib had the best effect on overall survival (OS) (hazards ratio [HR] = 0.42, 95% confidence interval [CI] = 0.18-0.98), lenvatinib 18 mg/d has the best effect on progression-free survival (PFS) (HR = 0.13, 95% CI = 0.064-0.27), and cabozantinib 60 mg/d has the best safety profile.
CONCLUSIONS
Our network meta-analysis showed that we believe that cabozantinib has the potential to become a widely used drug in clinical practice.
Topics: Humans; Tyrosine Kinase Inhibitors; Network Meta-Analysis; Randomized Controlled Trials as Topic; Anilides; Neoplasms; Pyridines
PubMed: 38608050
DOI: 10.1097/MD.0000000000037655