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Frontiers in Public Health 2024Antimicrobial resistance (AMR) is a major public health threat. With the growing emphasis on patient-centred care/ shared decision making, it is important for healthcare...
INTRODUCTION
Antimicrobial resistance (AMR) is a major public health threat. With the growing emphasis on patient-centred care/ shared decision making, it is important for healthcare professionals' (HCPs) who prescribe, dispense, administer and/or monitor antimicrobials to be adequately equipped to facilitate appropriate antimicrobial use. We systematically identified existing interventions which aim to improve HCPs interaction with patients and examined barriers and facilitators of appropriate the use of such interventions and appropriate antimicrobial use among both HCPs and patientsantimicrobial use while using these interventions.
METHODS
We searched MEDLINE, EMBASE, Web of Science, Google Scholar, and internet (via Google search engine). We included primary studies, published in English from 2010 to 2023 [PROSPERO (CRD42023395642)]. The protocol was preregistered with PROSPERO (CRD42023395642). We performed quality assessment using mixed methods appraisal tool. We applied narrative synthesis and used the COM-B (Capability, Opportunity, Motivation -Behaviour) as a theoretical framework for barriers and facilitators at HCP and patient levels.
RESULTS
Of 9,172 citations retrieved from database searches, From 4,979 citations remained after removal of duplicates. We included 59 studies spanning over 13 countries. Interventions often involved multiple components beyond HCPs' interaction with patients. From 24 studies reporting barriers and facilitators, we identified issues relating to capability (such as, knowledge/understanding about AMR, diagnostic uncertainties, awareness of interventions and forgetfulness); opportunity (such as, time constraint and intervention accessibility) and motivation (such as, patient's desire for antibiotics and fear of litigation).
CONCLUSION
The findings of this review should be considered by intervention designers/adopters and policy makers to improve utilisation and effectiveness.
Topics: Humans; Health Personnel; Professional-Patient Relations; Anti-Bacterial Agents; Drug Resistance, Bacterial
PubMed: 38841670
DOI: 10.3389/fpubh.2024.1359790 -
Frontiers in Pharmacology 2024In recent years, graph neural network has been extensively applied to drug discovery research. Although researchers have made significant progress in this field, there...
INTRODUCTION
In recent years, graph neural network has been extensively applied to drug discovery research. Although researchers have made significant progress in this field, there is less research on bibliometrics. The purpose of this study is to conduct a comprehensive bibliometric analysis of graph neural network applications in drug discovery in order to identify current research hotspots and trends, as well as serve as a reference for future research.
METHODS
Publications from 2017 to 2023 about the application of graph neural network in drug discovery were collected from the Web of Science Core Collection. Bibliometrix, VOSviewer, and Citespace were mainly used for bibliometric studies.
RESULTS AND DISCUSSION
In this paper, a total of 652 papers from 48 countries/regions were included. Research interest in this field is continuously increasing. China and the United States have a significant advantage in terms of funding, the number of publications, and collaborations with other institutions and countries. Although some cooperation networks have been formed in this field, extensive worldwide cooperation still needs to be strengthened. The results of the keyword analysis clarified that graph neural network has primarily been applied to drug-target interaction, drug repurposing, and drug-drug interaction, while graph convolutional neural network and its related optimization methods are currently the core algorithms in this field. Data availability and ethical supervision, balancing computing resources, and developing novel graph neural network models with better interpretability are the key technical issues currently faced. This paper analyzes the current state, hot spots, and trends of graph neural network applications in drug discovery through bibliometric approaches, as well as the current issues and challenges in this field. These findings provide researchers with valuable insights on the current status and future directions of this field.
PubMed: 38799167
DOI: 10.3389/fphar.2024.1393415 -
Pharmaceuticals (Basel, Switzerland) May 2024Although the dopamine hypothesis of schizophrenia explains the effects of all the available antipsychotics in clinical use, there is an increasing need for developing... (Review)
Review
Although the dopamine hypothesis of schizophrenia explains the effects of all the available antipsychotics in clinical use, there is an increasing need for developing new drugs for the treatment of the positive, negative, and cognitive symptoms of chronic psychoses. Xanomeline-trospium (KarXT) is a drug combination that is based on the essential role played by acetylcholine in the regulation of cognitive processes and the interactions between this neurotransmitter and other signaling pathways in the central nervous system, with a potential role in the onset of schizophrenia, Alzheimer's disease, and substance use disorders. A systematic literature review that included four electronic databases (PubMed, Cochrane, Clarivate/Web of Science, and Google Scholar) and the US National Library of Medicine database for clinical trials detected twenty-one sources referring to fourteen studies focused on KarXT, out of which only four have available results. Based on the results of these trials, the short-term efficacy and tolerability of xanomeline-trospium are good, but more data are needed before this drug combination may be recommended for clinical use. However, on a theoretical level, the exploration of KarXT is useful for increasing the interest of researchers in finding new, non-dopaminergic, antipsychotics that could be used either as monotherapy or as add-on drugs.
PubMed: 38794180
DOI: 10.3390/ph17050610 -
International Journal of Molecular... May 2024Breast cancer, the most invasive cancer in women globally, necessitates novel treatments due to prevailing limitations of therapeutics. Search of news anticancer targets... (Review)
Review
Breast cancer, the most invasive cancer in women globally, necessitates novel treatments due to prevailing limitations of therapeutics. Search of news anticancer targets is more necessary than ever to tackle this pathology. Heat-Shock Protein 90 (HSP90), a chaperone protein, is implicated in breast cancer pathogenesis, rendering it an appealing target. Looking for alternative approach such as Plant-based compounds and natural HSP90 inhibitors offer promising prospects for innovative therapeutic strategies. This study aims to identify plant-based compounds with anticancer effects on breast cancer models and elucidate their mechanism of action in inhibiting the HSP90 protein. A systematic review was conducted and completed in January 2024 and included in vitro, in vivo, and in silico studies that investigated the effectiveness of plant-based HSP90 inhibitors tested on breast cancer models. Eleven studies were included in the review. Six plants and 24 compounds from six different classes were identified and proved to be effective against HSP90 in breast cancer models. The studied plant extracts showed a dose- and time-dependent decrease in cell viability. Variable IC50 values showed antiproliferative effects, with the plant demonstrating the lowest value. Withanolides was the most studied class. Fennel, , and extracts were shown to inhibit tumor growth and angiogenesis and modulate HSP90 expression as well as its cochaperone interactions in breast cancer mouse models. The identified plant extracts and compounds were proven effective against HSP90 in breast cancer models, and this inhibition showed promising effects on breast cancer biology. Collectively, these results urge the need of further studies to better understand the mechanism of action of HSP90 inhibitors using comparable methods for preclinical observations.
Topics: Animals; Female; Humans; Antineoplastic Agents, Phytogenic; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Cell Survival; HSP90 Heat-Shock Proteins; Plant Extracts; Neoplasms, Experimental
PubMed: 38791506
DOI: 10.3390/ijms25105468 -
Contraception May 2024To summarize and update information regarding drug-drug interactions (DDIs) between antiretrovirals (ARVs) and hormonal contraceptives (HCs). (Review)
Review
OBJECTIVE
To summarize and update information regarding drug-drug interactions (DDIs) between antiretrovirals (ARVs) and hormonal contraceptives (HCs).
DESIGN
Systematic review METHODS: We searched seven databases for peer-reviewed publications from January 1, 2015, through December 31, 2023, including studies of women using ARVs and HCs concurrently with outcomes including therapeutic effectiveness or toxicity, pharmacokinetics (PK), or pharmacodynamics. We summarized findings and used checklists to assess evidence quality.
RESULTS
We included 49 articles, with clinical, ARV or HC PK outcomes reported by 39, 25, and 30 articles, respectively, with some articles reporting outcomes in two or more categories. Fifteen of 18 articles assessing DDIs between efavirenz and progestin implants, emergency contraception, or combined hormonal intravaginal rings found higher pregnancy rates, luteal progesterone levels suggesting ovulation, or reduced progestin PK values. Five studies documented that CYP2B6 single nucleotide polymorphisms exacerbated this DDI. One cohort detected doubled bone density loss with concomitant depot medroxyprogesterone acetate (DMPA) and tenofovir disoproxil fumarate (TDF)-containing ART use versus TDF alone. No other studies described DDIs impacting clinical outcomes. Few adverse events were attributed to ARV-HC use with none exceeding Grade 2. Evidence quality was generally moderate, with dis-similar treatment and control groups, identifying and controlling for confounding, and minimizing attrition bias in the study design being the most frequent limitations.
CONCLUSION
Most ARVs and HCs may be used safely and effectively together. TDF-DMPA DDIs warrant longer-term study on bone health and consideration of alternate combinations. For efavirenz-based ART, client counselling on relative risks, including both potential increase in pregnancy rate with concomitant efavirenz and implant use and lower pregnancy rates compared to other HCs even with concomitant efavirenz use, should continue to allow users comprehensive method choice.
PubMed: 38762199
DOI: 10.1016/j.contraception.2024.110490 -
Breast fat grafting and cancer: a systematic review of the science behind enhancements and concerns.Translational Breast Cancer Research :... 2024Autologous fat transfer (AFT) is gaining popularity in breast surgery, offering a natural-looking and minimally invasive approach for augmentation, reconstruction, and... (Review)
Review
BACKGROUND
Autologous fat transfer (AFT) is gaining popularity in breast surgery, offering a natural-looking and minimally invasive approach for augmentation, reconstruction, and contouring. However, concerns about its impact on breast cancer necessitate an understanding of the interplay between transplanted adipose-derived stem cells (ADSCs) and the breast tissue microenvironment. Renowned for regeneration, ADSCs raise questions about their role in cancer promotion. This systematic review delves into the complex relationship between AFT and breast cancer, exploring how ADSCs may influence development, growth, and metastasis.
METHODS
A systematic search of electronic databases, including PubMed, Embase, and BVS was conducted to identify relevant studies. The search strategy employed a combination of keywords, including "breast augmentation", "fat grafting", "breast enhancement", "mammoplasty", "cancer", "neoplasm" and related terms. Two reviewers independently screened titles and abstracts. Full-text articles were then retrieved for further evaluation based on their potential contribution to the review objectives.
RESULTS
Two hundred and forty records were identified. Among these, 104 duplicates were removed, resulting in 136 reports available for title and abstract screening. Subsequently, 54 papers were deemed potentially eligible for inclusion, and all reports were retrieved.
CONCLUSIONS
studies reveal ADSCs dual role in breast cancer, influencing proliferation, migration, and drug resistance through complex signaling pathways. Animal studies highlight distinct ADSC subpopulations impacting tumor growth via direct interactions and extracellular vesicle cargo. , ADSC-enriched fat grafting is generally safe, showing no increased cancer recurrence risk compared to other methods. Notably, cases of invasive breast carcinoma warrant special attention. ADSC-enriched fat grafts exhibit potential benefits in graft retention and survival rates. Despite promising evidence, further studies are needed to comprehensively understand the intricate relationship between ADSCs and breast cancer for optimized clinical applications and potential therapeutic innovations.
PubMed: 38751673
DOI: 10.21037/tbcr-23-54 -
BJA Open Jun 2024Local anaesthetics are widely used for their analgesic and anaesthetic properties in the perioperative setting, including surgical procedures to excise malignant... (Review)
Review
BACKGROUND
Local anaesthetics are widely used for their analgesic and anaesthetic properties in the perioperative setting, including surgical procedures to excise malignant tumours. Simultaneously, chemotherapeutic agents remain a cornerstone of cancer treatment, targeting rapidly dividing cancer cells to inhibit tumour growth. The potential interactions between these two drug classes have drawn increasing attention and there are oncological surgical contexts where their combined use could be considered. This review examines existing evidence regarding the interactions between local anaesthetics and chemotherapeutic agents, including biological mechanisms and clinical implications.
METHODS
A systematic search of electronic databases was performed as per Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Selection criteria were designed to capture , , and clinical studies assessing interactions between local anaesthetics and a wide variety of chemotherapeutic agents. Screening and data extraction were performed independently by two reviewers. The data were synthesised using a narrative approach because of the anticipated heterogeneity of included studies.
RESULTS
Initial searches yielded 1225 relevant articles for screening, of which 43 met the inclusion criteria. The interactions between local anaesthetics and chemotherapeutic agents were diverse and multifaceted. studies frequently demonstrated altered cytotoxicity profiles when these agents were combined, with variations depending on the specific drug combination and cancer cell type. Mechanistically, some interactions were attributed to modifications in efflux pump activity, tumour suppressor gene expression, or alterations in cellular signalling pathways associated with tumour promotion. A large majority of studies report potentially beneficial effects of local anaesthetics in terms of enhancing the antineoplastic activity of chemotherapeutic agents. In animal models, the combined administration of local anaesthetics and chemotherapeutic agents showed largely beneficial effects on tumour growth, metastasis, and overall survival. Notably, no clinical study examining the possible interactions of local anaesthetics and chemotherapy on cancer outcomes has been reported.
CONCLUSIONS
Reported preclinical interactions between local anaesthetics and chemotherapeutic agents are complex and encompass a spectrum of effects which are largely, although not uniformly, additive or synergistic. The clinical implications of these interactions remain unclear because of the lack of prospective trials. Nonetheless, the modulation of chemotherapy effects by local anaesthetics warrants further clinical investigation in the context of cancer surgery where they could be used together.
CLINICAL TRIAL REGISTRATION
Open Science Framework (OSF, project link: https://osf.io/r2u4z).
PubMed: 38741694
DOI: 10.1016/j.bjao.2024.100284 -
Clinical and Translational Science May 2024Cannabis-drug interactions have caused significant concerns, mainly due to their role in the cytochrome P450 (CYP) enzyme-mediated metabolic pathway of numerous...
Cannabis-drug interactions have caused significant concerns, mainly due to their role in the cytochrome P450 (CYP) enzyme-mediated metabolic pathway of numerous medications. A systematic review was conducted to gain an overview of the potential interactions of cannabis with different drug classes by extracting pertinent information from published study data. From the inception of the study to October 1, 2023, we performed a systematic search of PubMed, Scopus, clinicaltrials.gov, and Web of Science. We included 54 out of 464 articles, and a total of 20 drug classes were identified to have interactions with medicinal cannabis. The cannabis-drug interactions were assessed and classified according to their probability and severity. The analysis revealed that antiepileptics had the most evidence of interaction with cannabis, followed by clobazam (CLB), warfarin, and tacrolimus. Generally, cannabis-drug interactions result in pharmacokinetic (PK) or pharmacodynamic (PD) changes. Therefore, careful monitoring should be performed to detect any unusual elevations in plasma levels. In addition, dose titrations or treatment withdrawal could help mitigate the adverse effects attributed to cannabis-drug interactions. Nevertheless, novel drugs are constantly emerging, and more research is needed to further identify potential interactions with cannabis.
Topics: Humans; Anticonvulsants; Clobazam; Drug Interactions; Medical Marijuana; Warfarin
PubMed: 38720531
DOI: 10.1111/cts.13812 -
Frontiers in Endocrinology 2024Despite the developments of fertilization (IVF) protocols, implantation failure remains a challenging problem, owing to the unbalance between the embryo, endometrium,... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Despite the developments of fertilization (IVF) protocols, implantation failure remains a challenging problem, owing to the unbalance between the embryo, endometrium, and immune system interactions. Effective treatments are urgently required to improve successful implantation. Recently, many researchers have focused on granulocyte colony-stimulating factor (G-CSF) to regulate immune response and embryo-endometrium cross-talk. However, previous studies have reported inconsistent findings on the efficacy of G-CSF therapy on implantation failure. The objective of this review was to further explore the effects of G-CSF according to administration dosage and timing among women who experienced at least one implantation failure.
METHODS
We systematically searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Scopus, and Web of Science for randomized controlled trials of G-CSF on implantation failure up to July 21, 2023. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated and the heterogeneity of the studies with the I index was analyzed.
RESULTS
We identified a total of 2031 studies and finally included 10 studies in the systematic review and meta-analysis. G-CSF administration improved the clinical pregnancy rate (CPR), implantation rate (IR), biochemical pregnancy rate (BPR), and live birth rate (LBR) in women with at least one implantation failure. Subgroup analyses showed that G-CSF treatment could exert good advantages in improving CPR [OR=2.49, 95%CI (1.56, 3.98), I = 0%], IR [OR=2.82, 95%CI (1.29, 6.15)], BPR [OR=3.30, 95%CI (1.42, 7.67)] and LBR [OR=3.16, 95%CI (1.61, 6.22), I = 0%] compared with the blank control group. However, compared with placebo controls, G-CSF showed beneficial effects on CPR [OR=1.71, 95%CI (1.04, 2.84), I = 38%] and IR [OR=2.01, 95%CI (1.29, 3.15), I = 24%], but not on LBR. In addition, >150μg of G-CSF treatment increased CPR [OR=2.22, 95%CI (1.47, 3.35), I = 0%], IR [OR=2.67, 95%CI (1.47, 4.82), I = 0%] and BPR [OR=2.02, 95%CI (1.17, 3.47), I = 22%], while ≤150μg of G-CSF treatment improved miscarriage rate (MR) [OR=0.14, 95%CI (0.05, 0.38), I = 0%] and LBR [OR=2.65, 95%CI (1.56, 4.51), I = 0%]. Moreover, G-CSF administration on the day of embryo transfer (ET) could increase CPR [OR=2.81, 95%CI (1.37, 5.75), I = 0%], but not on the day of ovum pick-up (OPU) or human chorionic gonadotropin (HCG) injection.
CONCLUSION
G-CSF has a beneficial effect on pregnancy outcomes to some extent among women who experienced at least one implantation failure, and the administration dosage and timing influence the effect size. https://www.crd.york.ac.uk/prospero/, identifier CRD42023447046.
Topics: Humans; Female; Granulocyte Colony-Stimulating Factor; Embryo Implantation; Pregnancy; Pregnancy Rate; Fertilization in Vitro; Embryo Transfer; Randomized Controlled Trials as Topic; Treatment Failure
PubMed: 38694938
DOI: 10.3389/fendo.2024.1370114 -
BMC Psychiatry Apr 2024Given the inconsistencies in current studies regarding the impact of FKBP5 gene polymorphisms on depression, arising from variations in study methods, subjects, and...
BACKGROUND
Given the inconsistencies in current studies regarding the impact of FKBP5 gene polymorphisms on depression, arising from variations in study methods, subjects, and treatment strategies, this paper provides a comprehensive review of the relationship between FKBP5 gene polymorphisms and genetic susceptibility to depression, as well as their influence on response to antidepressant treatment.
METHODS
Electronic databases were searched up to April 11, 2023, for all literature in English and Chinese on depression, FKBP5 gene polymorphisms, and antidepressant treatment. Data extraction and quality assessment were performed for key study characteristics. Qualitative methods were used to synthesize the study results.
RESULTS
A total of 21 studies were included, with the majority exhibiting average to moderate quality. Six SNPs (rs3800373, rs1360780, rs9470080, rs4713916, rs9296158, rs9394309) were broadly implicated in susceptibility to depression, while rs1360780 and rs3800373 were linked to antidepressant treatment sensitivity. Additionally, rs1360780 was associated with adverse reactions to antidepressant drug treatment. However, these associations were largely unconfirmed in replication studies.
CONCLUSIONS
Depression is recognized as a polygenic genetic disorder, with multiple genes contributing, each exerting relatively small effects. Future studies should explore not only multiple gene interactions but also epigenetic changes. Presently, research on FKBP5 in affective disorders remains notably limited, highlighting the necessity for further investigations in this domain.
Topics: Humans; Antidepressive Agents; Depression; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide
PubMed: 38609904
DOI: 10.1186/s12888-024-05717-z