Pharmacokinetics and pharmacodynamics of antifungals in children and their clinical implications

Invasive fungal infections are a significant cause of morbidity and mortality in children. Successful management of these systemic infections requires identification of the causative pathogen, appropriate antifungal selection, and optimisation of its pharmacokinetic and pharmacodynamic properties to maximise its antifungal activity and minimise toxicity and the emergence of resistance. This review highlights salient scientific advancements in paediatric antifungal pharmacotherapies and focuses on pharmacokinetic and pharmacodynamic studies that underpin current clinical decision making. Four classes of drugs are widely used in the treatment of invasive fungal infections in children, including the polyenes, triazoles, pyrimidine analogues and echinocandins. Several lipidic formulations of the polyene amphotericin B have substantially reduced the toxicity associated with the traditional amphotericin B formulation. Monotherapy with the pyrimidine analogue flucytosine rapidly promotes the emergence of resistance and cannot be recommended. However, when used in combination with other antifungal agents, therapeutic drug monitoring of flucytosine has been shown to reduce high peak flucytosine concentrations, which are strongly associated with toxicity. The triazoles feature large inter-individual pharmacokinetic variability, although this pattern is less pronounced with fluconazole. In clinical trials, posaconazole was associated with fewer adverse effects than other members of the triazole family, though both posaconazole and itraconazole display erratic absorption that is influenced by gastric pH and the gastric emptying rate. Limited data suggest that the clinical response to therapy may be improved with higher plasma posaconazole and itraconazole concentrations. For voriconazole, pharmacokinetic studies among children have revealed that children require twice the recommended adult dose to achieve comparable blood concentrations. Voriconazole clearance is also affected by the cytochrome P450 (CYP) 2C19 genotype and hepatic impairment. Therapeutic drug monitoring is recommended as voriconazole pharmacokinetics are highly variable and small dose increases can result in marked changes in plasma concentrations. For the echinocandins, the primary source of pharmacokinetic variability stems from an age-dependent decrease in clearance with increasing age. Consequently, young children require larger doses per kilogram of body weight than older children and adults. Routine therapeutic drug monitoring for the echinocandins is not recommended. The effectiveness of many systemic antifungal agents has been correlated with pharmacodynamic targets in in vitro and in murine models of invasive candidiasis and aspergillosis. Further study is needed to translate these findings into optimal dosing regimens for children and to understand how these agents interact when multiple antifungal agents are used in combination

Effects and Mechanisms of Medicinal Plants on Healing Scars: A Systematic Review

Background: Scars can be a cosmetic disfigurement and can tremendously impact psychological, emotional, and social well-being. Some medicinal plants exert anti-scar properties via various mechanisms of action, many of which have not been clearly defined. Objective: This study will evaluate the effects of these medicinal plants with anti-scar properties and review the known underlying mechanisms related to the treatment and prevention of hypertrophic scars. Methods: The keywords used in the literature search included (Wound healing OR Re-epithelialization OR Regeneration) and (Medicinal plants OR Phyto* OR herb) and (Cytokines OR Collagen OR Fibroblasts). Publications indexed in the Institute for Scientific Information (ISI) and PubMed databases were included in the review. Articles with no accessible full texts, non-English language articles, review articles, studies with non-positive effects, and studies that were not related to the study’s aim were excluded from the study. The agreement for exclusion required all authors to concur. Finally, after reviewing all available literature, 61 articles were included in this systematic review. Results: Currently available evidence shows that medicinal plants and their derivatives seem to have properties that can prevent hypertrophic scars. This is achieved by accelerating the scar healing process, reducing inflammatory cytokines, suppressing proliferation, and inducing apoptosis in scar fibroblasts by regulating several signaling pathways. Additionally, they can reduce collagen deposition and have antimicrobial effects at the wound site. Conclusion: Topical use of medicinal plants as complementary medicine with varying mechanisms of action can reduce scar formation. They exert these properties mainly due to their anti-inflammatory, antioxidant, and antimicrobial properties. Therefore, these mechanisms reduce the healing time of the wound and thus prevent the formation of hypertrophic scars. Medicinal plants can be used safely and efficiently when applied topically to improve or prevent hypertrophic scar

Effect of Probiotics on Urinary Tract Infections in Children: A Systematic Review and Meta-Analysis

Background: Urinary tract infections (UTIs) are the most prevalent bacterial infections that occur in children worldwide. Objective: This meta-analysis aims to investigate the utility of probiotics as preventive therapy in children with a UTI. Methods: The Web of Science, PubMed, and Scopus were searched for articles that investigated the relationship between probiotic consumption and the risk of UTIs. The quality of the articles was evaluated using the Jadad scale. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a random-effects model. Subgroup analyses and sensitivity analyses were also conducted. The Cochran Q test and the statistic I2 were used to evaluate heterogeneity. To determine any potential publication bias, the Egger\u27s and Begg\u27s tests were used. Results: In total, eleven studies were selected for systematic review and meta-analysis. Compared to children who did not receive probiotics, the OR of developing or having a recurring urinary tract infection in those who received probiotics was 0.94 (95% CI; 0.88-0.999; p-value=0.046). The Begg\u27s and Egger\u27s tests showed no evidence of publication bias between probiotics and the risk of developing new or recurring urinary tract infections. Conclusion: Based on this systematic review and meta-analysis, probiotics could be an alternative therapy for children who are at risk of developing a UTI. They are non-pharmaceutical options and could be used as natural prophylaxis for UTIs. However, the currently published evidence does not irrefutably confirm that probiotics provide a protective effect against urinary bacterial infections. Therefore, there need to be large-scale randomized clinical trials undertaken to investigate the possible prophylaxis of probiotics. (Copyright© Bentham Science Publishers; For any queries, please email at [email protected].

Effect of Probiotics on Urinary Tract Infections in Children: A Systematic Review and Meta-Analysis

Background: Urinary tract infections (UTIs) are the most prevalent bacterial infections that occur in children worldwide. Objective: This meta-analysis aims to investigate the utility of probiotics as preventive therapy in children with a UTI. Methods: The Web of Science, PubMed, and Scopus were searched for articles that investigated the relationship between probiotic consumption and the risk of UTIs. The quality of the articles was evaluated using the Jadad scale. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a random-effects model. Subgroup analyses and sensitivity analyses were also conducted. The Cochran Q test and the statistic I2 were used to evaluate heterogeneity. To determine any potential publication bias, the Egger\u27s and Begg\u27s tests were used. Results: In total, eleven studies were selected for systematic review and meta-analysis. Compared to children who did not receive probiotics, the OR of developing or having a recurring urinary tract infection in those who received probiotics was 0.94 (95% CI; 0.88-0.999; p-value=0.046). The Begg\u27s and Egger\u27s tests showed no evidence of publication bias between probiotics and the risk of developing new or recurring urinary tract infections. Conclusion: Based on this systematic review and meta-analysis, probiotics could be an alternative therapy for children who are at risk of developing a UTI. They are non-pharmaceutical options and could be used as natural prophylaxis for UTIs. However, the currently published evidence does not irrefutably confirm that probiotics provide a protective effect against urinary bacterial infections. Therefore, there need to be large-scale randomized clinical trials undertaken to investigate the possible prophylaxis of probiotics. (Copyright© Bentham Science Publishers; For any queries, please email at [email protected].

Effect of probiotics on urinary tract infections in children: A systematic review and meta-analysis

Background: Urinary tract infections (UTIs) are the most prevalent bacterial infections that occur in children worldwide. Objective: This meta-analysis aims to investigate the utility of probiotics as preventive therapy in children with a UTI. Methods: The Web of Science, PubMed, and Scopus were searched for articles that investigated the relationship between probiotic consumption and the risk of UTIs. The quality of the articles was evaluated using the Jadad scale. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a random-effects model. Subgroup analyses and sensitivity analyses were also conducted. The Cochran Q test and the statistic I2 were used to evaluate heterogeneity. To determine any potential publication bias, the Egger's and Begg's tests were used. Results: In total, eleven studies were selected for systematic review and meta-analysis. Compared to children who did not receive probiotics, the OR of developing or having a recurring urinary tract infection in those who received probiotics was 0.94 (95% CI; 0.88-0.999; p-value=0.046). The Begg's and Egger's tests showed no evidence of publication bias between probiotics and the risk of developing new or recurring urinary tract infections. Conclusion: Based on this systematic review and meta-analysis, probiotics could be an alternative therapy for children who are at risk of developing a UTI. They are non-pharmaceutical options and could be used as natural prophylaxis for UTIs. However, the currently published evidence does not irrefutably confirm that probiotics provide a protective effect against urinary bacterial infections. Therefore, there need to be large-scale randomized clinical trials undertaken to investigate the possible prophylaxis of probiotics. Keywords: Child; Lactobacillus; Meta-analysis; Probiotics; Systematic review; Urinary tract infections

Effectiveness of Phosphodiesterase Type 5 Inhibitors on the Treatment of Thin Endometrium and Pregnancy Outcomes: An Systematic Review

Phosphodiesterase type 5 (PDE5) inhibitors are thought to play a role in increasing endometrial thickness and increasing the success rate of pregnancy outcomes. This study was done to investigate the effects of PDE5 inhibitors on infertile women with thin endometrium and pregnancy outcomes. In this systematic review, all randomized controlled trials (RCTs) and observational studies were retrieved from databases including Institute for Scientific Information (ISI), PubMed, and Scopus by interesting keywords. A checklist was designed to collect necessary data and pregnancy outcomes, and the required items were recorded. PDE5 inhibitors through various mechanisms such as induction of vasodilatory effect through the effect on NO/cGMP signaling on vascular smooth muscle, through regulating cells proliferation and induction angiogenesis by increasing the expression of tumor suppressor factor (p53), and vascular endothelial growth factor A (VEGF-A) and downregulating inflammation by downregulating proinflammatory cytokines, affect endometrial thickness that eventually increases and pregnancy outcomes. Although PDE5s inhibitors increase endometrial thickness by different mechanisms, especially in women with thin endometrial, this does not necessarily mean that they induce a positive effect in all situations. However, their positive effects on pregnancy outcome may be affected by the time of administration, type of infertility treatment, underlying diseases such as pelvic disorders and inflammation. So in this regard, there are still ambiguous aspects that required further RCTs study in this area. [ABSTRACT FROM AUTHOR

Antibiotic dosing in pediatric critically ill patients

Despite being some of the most frequently utilized drugs in children, caregivers still commonly prescribe antibiotics in neonates and children based on dosing regimens linearly extrapolated from adults. Although this practice is not limited to antibiotics, specific concerns related to dosing inaccuracy for antibiotics are treatment failure, antimicrobial resistance, and maturational toxicity. In this chapter, we first discuss the simultaneous impact of maturation and critical illness on pediatric pharmacokinetics (PK), including the specific impact of major burns and extracorporeal equipment. Both aspects (maturation and critical illness) will play a significant role in the final, phenotypic PK in a given child. Second, a section on pharmacodynamics (PD) focuses on the developmental safety of antibiotics. Developmental PD aspects may result in differences in risk rate, or altogether different risks compared to adult observations. Third, some compound-specific PK/PD observations (aminoglycosides, vancomycin, meropenem) in neonates and children are discussed to further illustrate the complex interaction between physiology and pathophysiology, including the limitations of the currently available guidance. In the final part of the chapter, the contribution of PK modeling and simulation and advanced therapeutic drug monitoring is explored as a tool towards tailored pharmacotherapy in pediatric critically ill patients

Effectiveness of phosphodiesterase type 5 inhibitors on the treatment of thin endometrium and pregnancy outcomes: An systematic review

Phosphodiesterase type 5 (PDE5) inhibitors are thought to play a role in increasing endometrial thickness and increasing the success rate of pregnancy outcomes. This study was done to investigate the effects of PDE5 inhibitors on infertile women with thin endometrium and pregnancy outcomes. In this systematic review, all randomized controlled trials (RCTs) and observational studies were retrieved from databases including Institute for Scientific Information (ISI), PubMed, and Scopus by interesting keywords. A checklist was designed to collect necessary data and pregnancy outcomes, and the required items were recorded. PDE5 inhibitors through various mechanisms such as induction of vasodilatory effect through the effect on NO/cGMP signaling on vascular smooth muscle, through regulating cells proliferation and induction angiogenesis by increasing the expression of tumor suppressor factor (p53), and vascular endothelial growth factor A (VEGF-A) and downregulating inflammation by downregulating proinflammatory cytokines, affect endometrial thickness that eventually increases and pregnancy outcomes. Although PDE5s inhibitors increase endometrial thickness by different mechanisms, especially in women with thin endometrial, this does not necessarily mean that they induce a positive effect in all situations. However, their positive effects on pregnancy outcome may be affected by the time of administration, type of infertility treatment, underlying diseases such as pelvic disorders and inflammation. So in this regard, there are still ambiguous aspects that required further RCTs study in this area

Effectiveness of Phosphodiesterase Type 5 Inhibitors on the Treatment of Thin Endometrium and Pregnancy Outcomes: An Systematic Review

Phosphodiesterase type 5 (PDE5) inhibitors are thought to play a role in increasing endometrial thickness and increasing the success rate of pregnancy outcomes. This study was done to investigate the effects of PDE5 inhibitors on infertile women with thin endometrium and pregnancy outcomes. In this systematic review, all randomized controlled trials (RCTs) and observational studies were retrieved from databases including Institute for Scientific Information (ISI), PubMed, and Scopus by interesting keywords. A checklist was designed to collect necessary data and pregnancy outcomes, and the required items were recorded. PDE5 inhibitors through various mechanisms such as induction of vasodilatory effect through the effect on NO/cGMP signaling on vascular smooth muscle, through regulating cells proliferation and induction angiogenesis by increasing the expression of tumor suppressor factor (p53), and vascular endothelial growth factor A (VEGF-A) and downregulating inflammation by downregulating proinflammatory cytokines, affect endometrial thickness that eventually increases and pregnancy outcomes. Although PDE5s inhibitors increase endometrial thickness by different mechanisms, especially in women with thin endometrial, this does not necessarily mean that they induce a positive effect in all situations. However, their positive effects on pregnancy outcome may be affected by the time of administration, type of infertility treatment, underlying diseases such as pelvic disorders and inflammation. So in this regard, there are still ambiguous aspects that required further RCTs study in this area. [ABSTRACT FROM AUTHOR

sj-docx-1-pev-10.1177_22840265231219331 – Supplemental material for Effects of Curcuma longa (turmeric) and curcumin on the premenstrual syndrome and dysmenorrhea: A systematic review

Supplemental material, sj-docx-1-pev-10.1177_22840265231219331 for Effects of Curcuma longa (turmeric) and curcumin on the premenstrual syndrome and dysmenorrhea: A systematic review by Zahra Shabanian Boroujeni, Saeid Heidari-Soureshjani and Catherine MT Sherwin in Journal of Endometriosis and Pelvic Pain Disorders</p