The purpose of this study was to review the literature on the clinical use of voriconazole (VRC) in pediatric patients. MEDLINE, Embase, PubMed, Web of Science, and Cochrane Library were searched from January 1, 2000, to August 15, 2023 for relevant clinical studies on VRC use in pediatric patients. Data were collected based on inclusion and exclusion criteria, and a systematic review was performed on recent research related to the use of VRC in pediatric patients. This systematic review included a total of 35 observational studies among which there were 16 studies investigating factors influencing VRC plasma trough concentrations (Ctrough) in pediatric patients, 14 studies exploring VRC maintenance doses required to achieve target range of Ctrough, and 11 studies focusing on population pharmacokinetic (PPK) research of VRC in pediatric patients. Our study found that the Ctrough of VRC were influenced by both genetic and non-genetic factors. The optimal dosing of VRC was correlated with age in pediatric patients, and younger children usually required higher VRC doses to achieve target Ctrough compared to older children. Establishing a PPK model for VRC can assist in achieving more precise individualized dosing in children.

BACKGROUND: The existing literature indicates that repetitive transcranial magnetic stimulation (rTMS) can potentially enhance the prognosis of poststroke aphasia (PSA). Nevertheless, these investigations did not identify the most effective parameters or settings for achieving optimal treatment outcomes. This study involved a meta-analysis aimed to identify the optimal variables for rTMS in treating post-infarction aphasia to guide the use of rTMS in rehabilitating PSA.
METHODS: PubMed, Embase, and Cochrane Library databases were searched from inception to May 2023, and articles were reviewed manually using subject words and free words and supplemented with references from the included literature to obtain additional relevant literature. The search terms included \"poststroke aphasia\" and \"repetitive transcranial magnetic stimulation (rTMS)\" repetitive transcranial magnetic stimulation. Additionally, a review of the reference lists of previously published systematic reviews identified through the Cochrane Database of Systematic Reviews (search terms: poststroke aphasia, rTMS; restrictions: none) and PubMed (search terms: poststroke aphasia, rTMSs; restrictions: systematic review or meta-analysis) was performed. Information from studies involving different doses of rTMS in PSA was independently screened and extracted by 2 researchers.
RESULTS: This meta-analysis included 387 participants with PSA across 18 randomized controlled trials. The results showed that the total pulse had a trend toward a significant correlation with the treatment effect (P = 0.088), while all other variables did not correlate significantly. When rTMS was not grouped by stimulus parameter and location, our nonlinear results showed that when the total pulses were 40,000 (standardized mean difference (SMD):1.86, 95% credible interval (CrI) 0.50 to 3.33), the pulse/session was 1000 (SMD:1.05, 95% CrI 0.55-1.57), and an RMT of 80% (SMD:1.08, 95% CrI 0.60-1.57) had the best treatment effect. When rTMS was grouped by stimulus parameters and location, our nonlinear results showed that when the total low-frequency (LF)-rTMS-right inferior frontal gyrus (RIFG) pulse was 40,000 (SMD:1.76, 95% CrI:0.36-3.29), the pulse/session was 1000 (SMD:1.06, 95% CrI:0.54-1.59). Optimal results were obtained with an RMT of 80% (SMD:1.14, 95% CrI 0.54 - 1.76).
CONCLUSIONS: The optimal treatment effects of rTMS for PSA may be obtained with a total pulse of 40,000, a pulse/session of 1000, and an RMT of 80%. Further rigorous randomized controlled studies are required to substantiate the validity of these results.

UNASSIGNED: Over the past few decades, advances in traumatic brain injury (TBI) pathology research have dynamically enriched our knowledge. Therefore, we aimed to systematically elucidate the safety and efficacy of erythropoietin (EPO) dosing regimens in patients with TBI.
UNASSIGNED: Data search included PubMed, the Cochrane Library, Embase, Web of Science, and ClinicalTrials.gov for related research published before July 2022. The network meta-analysis was conducted using ADDIS 1.16.8, and the CINeMA tool was used to assess the quality level of evidence.
UNASSIGNED: A total of six RCTs involving 981 patients were included in the network meta-analysis. EPO did not significantly reduce mortality in patients with TBI, but its risk of death decreased with increasing dosage (odds ratio (OR) of 12,000u vs. placebo = 0.98, 95% CI: 0.03-40.34; OR of group 30,000u vs. placebo = 0.56, 95% CI: 0.06-5.88; OR of 40,000u vs. placebo = 0.35, 95% CI: 0.01-9.43; OR of 70,000u vs. placebo = 0.29, 95% CI: 0.01-9.26; OR of group 80,000u vs. placebo = 0.22, 95% CI: 0.00-7.45). A total of three studies involving 739 patients showed that EPO did not increase the incidence of deep vein thrombosis in patients with TBI. However, the risk tended to rise as the dosage increased. Another two studies demonstrated that EPO did not increase the incidence of pulmonary embolism. The quality of evidence for all outcomes was low to moderate.
UNASSIGNED: Although the efficacy of EPO was not statistically demonstrated, we found a trend toward an association between EPO dosage and reduced mortality and increased embolic events in patients with TBI. More high-quality original studies should be conducted to obtain strong evidence on the optimal dosage of EPO.
UNASSIGNED: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=272500. The study protocol was registered with PROSPERO (CRD42021272500).

BACKGROUND: There are no consensus guidelines on the optimal dose or injection site of botulinum toxin (BT) for chronic anal fissure (CAF). The objective of this study was to determine the appropriate dose and injection site of BT for CAF by comparing healing rate and adverse effects (incontinence and recurrence).
METHODS: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL) and Scopus were searched from inception through May 31, 2021. Randomized controlled trials evaluating healing and adverse effects of BT injection for CAF published in any language were selected. Multiple treatment comparisons and ranking were performed using a two-stage network meta-analysis, and results were graded by Confidence in Network Meta-Analysis tool.
RESULTS: Twenty-seven trials involving 1880 patients were included. The results demonstrated that high-dose-BT had significantly higher short-term healing when injected out of the fissure (OF) site than each side of the fissure (SF) site, with a risk ratio (RR) of 2.12 (1.08, 4.15); low-dose-BT did not show any difference across OF and SF site with RR of 1.20 (0.85, 1.68). High-dose-BT at the OF site showed similar healing to low-dose-BT at the same site (RR of 1.02 (0.79, 1.31)) but with a higher risk of incontinence with RR of 3.54 (0.85, 14.76). In contrast, high-dose-BT at the SF site showed lower healing compared to low-dose-BT at the same site with RR of 0.57 (0.29, 1.14). Both high-dose-BT and low-dose-BT at the OF site had higher recurrence than high-dose-BT or low-dose-BT at the SF site with RR of 2.08 (0.33, 13.11) and 1.89 (0.60, 5.94), respectively.
CONCLUSIONS: Given moderate level of evidence, low-dose BT is optimal; injection out of the fissure site improves short-term outcomes while injection each side of the fissure site tends to reduce recurrence in the longer term.

Background: Obsessive-compulsive disorder (OCD) is a common chronic mental disorder with a high disability rate. Serotonin reuptake inhibitors (SRIs), including selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants, such as clomipramine, are the most common choices for the pharmacological treatment of OCD. Optimizing their use is pivotal in guiding clinical practice of OCD. However, there are few studies on the optimal dose of SRIs and there is controversy about their dose-response relationship and optimal target dose. Therefore, the objective of this study was to summarize the relationship between the dose and effect of SRIs, as well as the optimal dose of SRIs for OCD, as to propose future research directions. Methods: Medline, Embase, Biosis, PsycINFO, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and CINAHL were searched for relevant publications, and the search was up to February 22, 2020. We used a one-stage, robust error meta-regression (REMR) model to deal with the correlated dose-response data for SRIs from different studies. Doses of SRIs were converted to fluoxetine equivalents when performing dose-response analysis. Review Manager Program Version 5.3 and STATA software package (version 15.1) were applied to analyze data. The study protocol was registered with PROSPERO (number CRD42020168344). Results: Eleven studies involving 2,322 participants were included in final analysis. For SRIs, the dose-efficacy curve showed a gradual increase trend in the 0-40-mg dose range and then had a decreased trend in doses up to 100 mg fluoxetine equivalent. Dropouts due to adverse effects gradually increased throughout the inspected dose slope. The curve of dose of all-cause dropouts suggested no relationship between them. Sensitivity analysis proved that these results were robust. Conclusion: The systematic review found that the optimal dose for efficacy was about 40mg fluoxetine equivalent. Tolerability decreased with increased doses, and there was no significant correlation between acceptability and doses of SRIs. Therefore, the optimal dose of SRIs needs to consider effectiveness and tolerability. Systematic Review Registration: [PROSPERO], identifier [CRD42020168344].

Post-stroke spasticity impedes patients\' rehabilitation progress. Contradictory evidence has been reported in using Botulinum Neurotoxin type A (BoNT-A) to manage post-stroke lower extremity spasticity (PLES); furthermore, an optimum dose of BoNT-A for PLES has not yet been established. Therefore, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to identify the efficacy and optimal dose of BoNT-A on PLES. \"Meta\" and \"Metafor\" packages in R were used to analyze the data. Hedges\' g statistic and random effect model were used to calculate and pool effect sizes. Twelve RCTs met the eligibility criteria. Muscle tone significantly improved in week four, week eight, and maintained to week twelve after BoNT-A injection. Improvements in functional outcomes were found, some inconsistencies among included studies were noticed. Dosage analysis from eight studies using Botox® and three studies using Dysport® indicated that the optimum dose for the commonest pattern of PLES (spastic plantar flexors) is medium-dose (approximately 300U Botox® or 1000 U Dysport®). BoNT-A should be regarded as part of a rehabilitation program for PLES. Furthermore, an optimal rehabilitation program combined with BoNT-A management needs to be established. Further studies should also focus on functional improvement by BoNT-A management in the early stage of stroke.