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Brazilian Journal of Microbiology :... Jun 2023Bacterial resistance to multiple drugs is a worldwide problem that afflicts public health. Various studies have shown that silver nanoparticles are good bactericidal... (Review)
Review
Bacterial resistance to multiple drugs is a worldwide problem that afflicts public health. Various studies have shown that silver nanoparticles are good bactericidal agents against bacteria due to the adherence and penetration of the external bacterial membrane, preventing different vital functions and subsequently bacterial cell death. A systematic review of ScienceDirect, PubMed, and EBSCOhost was conducted to synthesize the literature evidence on the association between the bactericidal property of silver nanoparticles on both resistant Gram-positive and Gram-negative bacteria. Eligible studies were original, comparative observational studies that reported results on drug-resistant bacteria. Two independent reviewers extracted the relevant information. Out of the initial 1 420, 142 studies met the inclusion criteria and were included to form the basis of the analysis. Full-text screening led to the selection of 6 articles for review. The results of this systematic review showed that silver nanoparticles act primarily as bacteriostatic agents and subsequently as bactericides, both in Gram-positive and Gram-negative drug-resistant bacteria.
Topics: Anti-Bacterial Agents; Silver; Metal Nanoparticles; Gram-Negative Bacteria; Gram-Positive Bacteria; Bacteria; Microbial Sensitivity Tests
PubMed: 37131105
DOI: 10.1007/s42770-023-00991-7 -
British Journal of Clinical Pharmacology Sep 2014The objective of this systematic review was to characterize the pharmacokinetics and pharmacodynamics of denosumab (XGEVA®), a fully human IgG2 monoclonal antibody... (Review)
Review
AIM
The objective of this systematic review was to characterize the pharmacokinetics and pharmacodynamics of denosumab (XGEVA®), a fully human IgG2 monoclonal antibody which binds to receptor activator of nuclear factor kappa-B ligand (RANKL), for the treatment of skeletal-related events (SREs) in patients with advanced cancer and bone metastases.
METHODS
A total of 708 patients (116 healthy patients and 592 patients with solid tumours or multiple myeloma and bone metastases) included in seven clinical studies were evaluated for denosumab pharmacokinetics. Denosumab was administered as a single subcutaneous (s.c.) dose or multiple s.c. doses, ranging from 0.1 to 3.0 mg kg(-1) or 30 mg to 180 mg fixed dosing, every 1 or 3 months for up to 45 months.
RESULTS
Consistent with the results in healthy adults, single s.c. doses of denosumab demonstrated dose-dependent, non-linear pharmacokinetics in advanced cancer patients with bone metastases across a wide dose range (0.1-3.0 mg kg(-1) ). Reductions in levels of the bone turnover marker, uNTx/Cr, were observed within 1 day. The duration of reductions generally increased with dose and dosing frequency. In patients with solid tumours and bone metastases, pharmacokinetics and pharmacodynamic comparisons across tumour types and concomitant cancer therapies (chemotherapies and/or hormone therapies) suggest that neither tumour type nor type of concomitant therapy markedly affects denosumab pharmacokinetics or pharmacodynamics.
CONCLUSIONS
Denosumab displayed non-linear pharmacokinetics at doses below 60 mg but at higher doses, denosumab exposure increased approximately dose-proportionally in advanced cancer patients with bone metastases. Following a 120 mg, every 4 weeks dosing schedule, similar denosumab pharmacokinetics and pharmacodynamics were observed across tumour types and were independent of concomitant cancer therapies.
Topics: Adult; Antibodies, Monoclonal, Humanized; Bone Neoplasms; Denosumab; Dose-Response Relationship, Drug; Humans; Neoplasms; RANK Ligand
PubMed: 24548274
DOI: 10.1111/bcp.12355 -
Pharmacoepidemiology and Drug Safety Aug 2016In order to identify challenges in pediatric pharmacoepidemiological safety studies, we assessed the characteristics of such (published) studies. (Review)
Review
PURPOSE
In order to identify challenges in pediatric pharmacoepidemiological safety studies, we assessed the characteristics of such (published) studies.
METHODS
Relevant articles from inception to 2013 were retrieved from Embase and Medline. We sequentially screened titles, abstracts and full texts with independent validation. We systematically collected data regarding general information, study methods and results.
RESULTS
Out of 4825 unique articles, 268 full texts (5.6%) were retained; 147 (54.9%) pertained to drugs rather than vaccines. Considering the 268 studies, 202 (75.4%) concerned children and adolescents (2 to 11 years) and 14 (5.3%) included preterm newborns. Most studies originated from North America (154 [57.5%]) or Europe (92 [34.3%]). Only 47 studies (17.5%) were privately funded. The majority (174 [64.9%]) were cohort studies. Out of 268 studies, 196 (73.1%) collected data retrospectively; paper medical charts were the most common data source for the exposures (85 [31.7%]) and outcomes (122 [45.5%]). Only 3 (2.0%) drug-only studies investigated rarely used drugs. Considering all 268 studies, only 27 (10.1%) reported sample size or power calculation. Most (75 [51.0%]) drug-only studies corrected confounding by multivariate modeling unlike stratification in 66 (55.9%) vaccine-only studies. Considering 75 child-only studies without any statistically significant result, 41 (54.7%) did not discuss lack of power.
CONCLUSIONS
Although the field of pediatric pharmacoepidemiology is steadily developing evaluation seldom includes neonates, is mainly focused on few drug classes and safety outcomes and concerns mainly drug use in developed countries. Small study size is a specific challenge in pediatrics. Reporting should be improved. © 2016 The Authors. Pharmacoepidemiology and Drug Safety Published by John Wiley & Sons Ltd.
Topics: Adolescent; Child; Confounding Factors, Epidemiologic; Data Collection; Drug-Related Side Effects and Adverse Reactions; Epidemiologic Research Design; Humans; Infant, Newborn; Multivariate Analysis; Pediatrics; Pharmacoepidemiology; Research Support as Topic
PubMed: 27255559
DOI: 10.1002/pds.4041 -
Journal of Medicine and Life Mar 2022The COVID-19 pandemic has tremendously increased the production and sales of disinfectants. This study aimed to systematically review and analyze the efficacy and safety... (Review)
Review
The COVID-19 pandemic has tremendously increased the production and sales of disinfectants. This study aimed to systematically review and analyze the efficacy and safety of chlorine dioxide as a disinfectant. The literature relating to the use of chlorine dioxide as a disinfectant was systematically reviewed in January 2021 using databases such as PubMed, Science Direct, and Google Scholar. Inclusion criteria were studies that investigated the use of chlorine dioxide to assess the efficacy, safety, and impact of chlorine dioxide as a disinfectant. Out of the 33 included studies, 14 studies focused on the disinfectant efficacy of chlorine dioxide, 8 studies expounded on the safety and toxicity in humans and animals, and 15 studies discussed the impact, such as water treatment disinfection using chlorine dioxide. Chlorine dioxide is a safe and effective disinfectant, even at concentrations as low as 20 to 30 mg/L. Moreover, the efficacy of chlorine dioxide is mostly independent of pH. Chlorine dioxide can be effectively used to disinfect drinking water without much alteration of palatability and can also be used to destroy pathogenic microbes, including viruses, bacteria, and fungi from vegetables and fruits. Our review confirms that chlorine dioxide is effective against the resistant , H1N1, and other influenza viruses. Studies generally support the use of chlorine dioxide as a disinfectant. The concentration deemed safe for usage still needs to be determined on a case-by-case basis.
Topics: Animals; COVID-19; Chlorine; Chlorine Compounds; Disinfectants; Humans; Influenza A Virus, H1N1 Subtype; Oxides; Pandemics
PubMed: 35449999
DOI: 10.25122/jml-2021-0180 -
The Journal of Clinical Pediatric... 2015Dexmedetomidine is a central α-2 agonist, similar to Clonidine, but 8 times more specific for the central α-2 receptor which causes sedation with minimal depression of... (Review)
Review
UNLABELLED
Dexmedetomidine is a central α-2 agonist, similar to Clonidine, but 8 times more specific for the central α-2 receptor which causes sedation with minimal depression of respiration, making it safe for sedation during procedures. It is widely used in the field of medicine for many procedures especially premedication, awake intubation, and sedation of patients in intensive care units and pediatric procedural sedation.
OBJECTIVE
To do a systematic review of the pharmacology, pharmacodynamics, as well as the usage of newer sedative drug- Dexmedetomidine in dentistry.
STUDY DESIGN
The search for articles was conducted in Pub Med, including the articles published in English until Oct 2014. Both animal and human studies were included using the key words, "Dexmedetomidine", "Dexmedetomidine in sedation", "Dexmedetomidine in Dentistry", and "Dexmedetomidine in Pediatric dentistry". The Articles obtained were checked for their quality methodology and inference of the studies and selected for review.
RESULTS
Initial search retrieved 2436 articles, out of which 44 articles were on the subject of Dexmedetomidine in dentistry. Five of which articles were on the usage of Dexmedetomidine in pediatric dentistry. These studies were included in systematic review.
CONCLUSION
The study revealed that Dexmedetomidine being a new drug with its added advantages makes a better choice for sedation in dentistry. But with limited studies on Dexmedetomidine, the recommendation to use the drug exclusively is still under debate.
Topics: Adrenergic alpha-2 Receptor Agonists; Anesthesia, Dental; Conscious Sedation; Dexmedetomidine; Humans; Hypnotics and Sedatives
PubMed: 26551360
DOI: 10.17796/1053-4628-39.5.401 -
Current Neuropharmacology 2023Traditional medicine and biomedical sciences are reaching a turning point because of the constantly growing impact and volume of Big Data. Machine Learning (ML)...
Traditional medicine and biomedical sciences are reaching a turning point because of the constantly growing impact and volume of Big Data. Machine Learning (ML) techniques and related algorithms play a central role as diagnostic, prognostic, and decision-making tools in this field. Another promising area becoming part of everyday clinical practice is personalized therapy and pharmacogenomics. Applying ML to pharmacogenomics opens new frontiers to tailored therapeutical strategies to help clinicians choose drugs with the best response and fewer side effects, operating with genetic information and combining it with the clinical profile. This systematic review aims to draw up the state-of-the-art ML applied to pharmacogenomics in psychiatry. Our research yielded fourteen papers; most were published in the last three years. The sample comprises 9,180 patients diagnosed with mood disorders, psychoses, or autism spectrum disorders. Prediction of drug response and prediction of side effects are the most frequently considered domains with the supervised ML technique, which first requires training and then testing. The random forest is the most used algorithm; it comprises several decision trees, reduces the training set's overfitting, and makes precise predictions. ML proved effective and reliable, especially when genetic and biodemographic information were integrated into the algorithm. Even though ML and pharmacogenomics are not part of everyday clinical practice yet, they will gain a unique role in the next future in improving personalized treatments in psychiatry.
Topics: Humans; Pharmacogenetics; Precision Medicine; Machine Learning; Mental Disorders; Psychiatry
PubMed: 37559539
DOI: 10.2174/1570159X21666230808170123 -
Immunity, Inflammation and Disease Aug 2023Lactoferrin is a versatile protein with important modulatory functions in inflammation and immune response. This glycoprotein can bind and sequester iron and LPS,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Lactoferrin is a versatile protein with important modulatory functions in inflammation and immune response. This glycoprotein can bind and sequester iron and LPS, thereby intervening in certain signaling pathways and biological processes. In the present meta-analysis, we aimed to pool experimental data regarding the immunomodulatory effects of lactoferrin and its derived peptides on the NF-κB signaling pathway.
MATERIALS
We searched PubMed, Google Scholar, and Web of Science databases and obtained all related articles published before April 2022. Finally, 25 eligible studies were selected, and their reports were analyzed.
METHODS
We used Review Manager Version 5.2 to compute the standardized mean difference (SMD) and its 95% confidence interval. In addition, the source of heterogeneity was explored using meta-regression and sensitivity analysis. The symmetry of the funnel plot and Egger's test were also used to evaluate publication bias utilizing Comprehensive Meta-Analysis Version 2.
RESULTS
Comparing the group of cells and animals exposed to lipopolysaccharide alone with the group that received pretreatment with lactoferrin and its derivatives, we observed significant reductions in TNF-α, IL-1 beta, and IL-6 levels by 8.73 pg/mL, 2.21 pg/mL, and 3.24 pg/mL, respectively, in the second group. Additionally, IKK-β, p-IκB, and NF-κB (p65) levels were significantly lower by 7.37-fold, 15.02-fold, and 3.88-fold, respectively, in various cells and tissues.
CONCLUSION
Based on the results of this meta-analysis, lactoferrin and its derived peptides can be considered potent prophylactic and therapeutic candidates against inflammation-associated diseases by targeting the NF-kB pathway.
Topics: Animals; NF-kappa B; Lactoferrin; Signal Transduction; Peptides; Inflammation; Lipopolysaccharides; Immunity
PubMed: 37647433
DOI: 10.1002/iid3.972 -
Journal of the Royal Society of Medicine Sep 2023The cardiorenal protective effects of sodium-glucose co-transporter 2 inhibitors (SGLT2-Is) and glucagon-like peptide 1 receptor agonists (GLP1-RAs) across racial and...
Racial, ethnic and regional differences in the effect of sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide 1 receptor agonists on cardiovascular and renal outcomes: a systematic review and meta-analysis of cardiovascular outcome trials.
OBJECTIVES
The cardiorenal protective effects of sodium-glucose co-transporter 2 inhibitors (SGLT2-Is) and glucagon-like peptide 1 receptor agonists (GLP1-RAs) across racial and ethnic groups are not well defined. By conducting a systematic review and meta-analysis of all randomised, placebo-controlled, cardiovascular disease (CVD) outcomes trials (CVOTs), we aimed to compare racial/ethnic as well as regional patterns in the effects of SGLT2-Is and GLP1-RAs on cardiovascular and renal outcomes in patients with type 2 diabetes (T2D).
DESIGN
Trials were identified from MEDLINE, Embase, the Cochrane Library, and search of bibliographies to 7 July 2023. Setting North America, South/Central America, Europe (Eastern and Western), Asia, Australia-New Zealand (Pacific), Asia/Pacific, and Africa.
SETTING
North America, South/Central America, Europe (Eastern and Western), Asia, Australia-New Zealand (Pacific), Asia/Pacific, and Africa.
PARTICIPANTS
people with type 2 diabetes enrolled in cardiovascular outcome trials of SGLT2-Is and GLP1-RAs.
MAIN OUTCOME MEASURES
Outcomes were (i) major adverse cardiovascular events (MACE), (ii) composite CVD death/heart failure (HF) hospitalization; (iii) composite renal outcome; and (iv) their components. Study-specific hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled.
RESULTS
In total, 14 unique CVOTs (7 comparing SGLT2-Is vs placebo and 7 comparing GLP1-RAs vs placebo) were eligible. The proportion of participants enrolled in the trials ranged from 66.6-93.2% for White populations, 1.2-21.6% for Asian populations, 2.4-8.3% for Black populations and 0.9-23.1% for Other populations. The HR (95% CI) for MACE comparing SGLT2-Is vs placebo was 0.92 (0.86-0.98), 0.69 (0.53-0.92) and 0.70 (0.54-0.91) for White, Asian and Hispanic/Latino populations, respectively. Comparing GLP1-RAs vs placebo, the corresponding HR (95% CI) was 0.88 (0.80-0.97), 0.76 (0.63-0.93) and 0.82 (0.70-0.95), respectively. SGLT2-Is reduced the risk of all other cardiorenal outcomes in White and Asian populations, except for HF hospitalizations in Asians. No effects were observed in Black populations except for a reduced risk of HF hospitalizations by SGLT2-I. SGLT1-Is reduced the risk of composite CVD death/HF hospitalization in North America and Europe, whereas GLP1-RAs reduced the risk of MACE in Europe. GRADE certainty of evidence ranged from moderate to high.
CONCLUSIONS
There appears to be substantial racial/ethnic differences in the cardiorenal effects of SGLT2-Is and GLP1-RAs in patients with T2D, with consistent benefits observed among White and Asian populations and consistent lack of benefits in Black populations. Whether the differences are due to issues with under-representation of Black populations and low statistical power or racial/ethnic variations in the pharmacokinetics, pharmacodynamics and safety of SGLT2-Is and GLP1-RAs need further investigation.PROSPERO Registration: CRD42023401734.
PubMed: 37734450
DOI: 10.1177/01410768231198442 -
PloS One 2016Several meta-analyses comparing ciclosporin with tacrolimus have been conducted since the 1994 publication of the tacrolimus registration trials, but most captured data... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND AND AIMS
Several meta-analyses comparing ciclosporin with tacrolimus have been conducted since the 1994 publication of the tacrolimus registration trials, but most captured data from randomized controlled trials (RCTs) predating recent improvements in waiting list prioritization, induction protocols and concomitant medications. The present study comprised a systematic review and meta-analysis of ciclosporin and tacrolimus in liver transplant recipients using studies published since January 2000.
METHODS
Searches of PubMed, the Cochrane Library and EMBASE identified RCTs of tacrolimus and ciclosporin as the immunosuppressant in adult primary liver transplant recipients, published between January 2000 and August 6, 2014. A random effects meta-analysis was conducted to evaluate the relative risk of death, graft loss, acute rejection (AR), new-onset diabetes after transplantation (NODAT) and hypertension with tacrolimus relative to ciclosporin at 12 months.
RESULTS
The literature search identified 11 RCTs comparing ciclosporin with tacrolimus. Relative to ciclosporin, tacrolimus was associated with significantly improved outcomes in terms of patient mortality (risk ratio [RR] with ciclosporin of 1.26; 95% confidence interval [95%CI] 1.01-1.58). Tacrolimus was superior to ciclosporin in terms of hypertension (RR with ciclosporin 1.26; 95%CI 1.07-1.47), but inferior in terms of NODAT (RR with ciclosporin 0.60; 95%CI 0.47-0.77). There were no significant differences between ciclosporin and tacrolimus in terms of graft loss or AR.
CONCLUSIONS
Meta-analysis of RCTs published since 2000 showed tacrolimus to be superior to ciclosporin in terms of patient mortality and hypertension, while ciclosporin was superior in terms of NODAT. No significant differences were identified in terms of graft loss or AR. These findings provide further evidence supporting the use of tacrolimus as the cornerstone of immunosuppressive therapy in liver transplant recipients.
Topics: Cyclosporine; Humans; Immunosuppressive Agents; Liver Transplantation; Randomized Controlled Trials as Topic; Tacrolimus
PubMed: 27812112
DOI: 10.1371/journal.pone.0160421 -
Cureus Jan 2023Midazolam nasal spray (MDZ-NS) is a new emerging rescue medication that suppresses epileptic seizures. Until now, few studies, pharmacokinetic (PK) and pharmacodynamic... (Review)
Review
Midazolam nasal spray (MDZ-NS) is a new emerging rescue medication that suppresses epileptic seizures. Until now, few studies, pharmacokinetic (PK) and pharmacodynamic (PD) profiles, and clinical trials have shown that midazolam nasal spray could become an effective and promising alternative to conventional routes (intravenous {IV}/rectal). Therefore, we thought of conducting a systematic review and meta-analysis of midazolam (MDZ) to assess its potential outcomes. The analysis was also evaluated based on the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of midazolam nasal spray. A systematic literature search was carried out through various databases to identify studies of accounted outcomes of midazolam nasal spray (MDZ-NS). Randomized and other studies of patients (12 years or older) with seizure clusters (SCs) were included. A total of three full-text articles were considered for systematic review and meta-analysis as per the inclusion and exclusion criteria. The 5 mg MDZ-NS was observed to be equally safe as a placebo, and the risk ratio (RR) was 1.01 (95% confidence interval (CI): 0.67-1.53). After the administration of MDZ-NS, either the patients remained seizure-free for six hours or more or the seizure was terminated within 10 minutes and had no recurrence between 10 minutes and six hours. The risk ratio (RR) obtained was 1.54 (95% CI: 1.25-1.91). The result was statistically significant as a higher success rate was observed with the use of 5 mg midazolam nasal spray compared to placebo (p < 0.0001). Heterogeneity was not observed in the results of the included studies (inconsistency index {I}: 0%). The present systematic review and meta-analysis demonstrated that 5 mg midazolam nasal spray was efficacious in treating patients with seizure clusters and is well-tolerated. Also, its use is relatively safe.
PubMed: 36843713
DOI: 10.7759/cureus.34064