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Frontiers in Veterinary Science 2022African animal trypanocide resistance (AATr) continues to undermine global efforts to eliminate the transmission of African trypanosomiasis in endemic communities. The...
BACKGROUND
African animal trypanocide resistance (AATr) continues to undermine global efforts to eliminate the transmission of African trypanosomiasis in endemic communities. The continued lack of new trypanocides has precipitated drug misuse and overuse, thus contributing to the development of the AATr phenotype. In this study, we investigated the threat associated with AATr by using the major globally available chemotherapeutical agents.
METHODS
A total of seven electronic databases were screened for an article on trypanocide resistance in AATr by using keywords on preclinical and clinical trials with the number of animals with treatment relapse, days taken to relapse, and resistant gene markers using the PRISMA checklist. Data were cleaned using the SR deduplicator and covidence and analyzed using Cochrane RevMan®. Dichotomous outputs were presented using risk ratio (RR), while continuous data were presented using the standardized mean difference (SMD) at a 95% confidence interval.
RESULTS
A total of eight publications in which diminazene aceturate (DA), isometamidium chloride (ISM), and homidium chloride/bromide (HB) were identified as the major trypanocides were used. In all preclinical studies, the development of resistance was in the order of HB > ISM > DA. DA vs. ISM (SMD = 0.15, 95% CI: -0.54, 0.83; = 46%, = 0.05), DA vs. HB (SMD = 0.96, 95% CI: 0.47, 1.45; = 0%, = 0.86), and HB vs. ISM (SMD = -0.41, 95% CI: -0.96, 0.14; = 5%, = 0.38) showed multiple cross-resistance. Clinical studies also showed evidence of multi-drug resistance on DA and ISM (RR = 1.01, 95% CI: 0.71-1.43; = 46%, = 0.16). To address resistance, most preclinical studies increased the dosage and the treatment time, and this failed to improve the patient's prognosis. Major markers of resistance explored include AT1, P1/P2 transporters, folate transporters, such as F-I, F-II, F-III, and polyamine biosynthesis inhibitors. In addition, immunosuppressed hosts favor the development of AATr.
CONCLUSION
AATr is a threat that requires a shift in the current disease control strategies in most developing nations due to inter-species transmission. Multi-drug cross-resistance against the only accessible trypanocides is a major public health risk, justifying the need to revise the policy in developing countries to promote control of African trypanosomiasis.
PubMed: 36686196
DOI: 10.3389/fvets.2022.950248 -
Metabolites Dec 2022Cancers are the leading cause of death worldwide. The most common cancers include breast, lung, and colorectum. Salivary metabolome profiling is a novel non-invasive... (Review)
Review
Cancers are the leading cause of death worldwide. The most common cancers include breast, lung, and colorectum. Salivary metabolome profiling is a novel non-invasive method in oncological diagnosis. This systematic review was designed to answer the question "Are salivary metabolites reliable for the diagnosis of systemic cancers?". Following the inclusion and exclusion criteria, nineteen studies were included (according to PRISMA statement guidelines). Changes in salivary metabolome were most commonly determined in patients with breast cancer, gastrointestinal cancers, and lung cancer. Most studies involved unstimulated whole saliva as the diagnostic material, evaluated by different spectroscopic methods. Among the found saliva metabolites, the alterations in the metabolic pathways of amino acids and polyamines were most frequently observed, which showed significant predictive values in oncological diagnostics. The most frequently encountered risks of bias were the absence of data regarding blinding, sample size justification, and randomisation. In conclusion, salivary metabolites seem to be potentially reliable for detecting the most common systemic cancers. However, further research is desirable to confirm these outcomes and to detect new potential metabolic biomarkers in saliva.
PubMed: 36676953
DOI: 10.3390/metabo13010028 -
Clinical Infectious Diseases : An... May 2023Optimal doses of first-line drugs for treatment of drug-susceptible tuberculosis in children and young adolescents remain uncertain. We aimed to determine whether... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Optimal doses of first-line drugs for treatment of drug-susceptible tuberculosis in children and young adolescents remain uncertain. We aimed to determine whether children treated using World Health Organization-recommended or higher doses of first-line drugs achieve successful outcomes and sufficient pharmacokinetic (PK) exposures.
METHODS
Titles, abstracts, and full-text articles were screened. We searched PubMed, EMBASE, CENTRAL, and trial registries from 2010 to 2021. We included studies in children aged <18 years being treated for drug-susceptible tuberculosis with rifampicin (RIF), pyrazinamide, isoniazid, and ethambutol. Outcomes were treatment success rates and drug exposures. The protocol for the systematic review was preregistered in PROSPERO (no. CRD42021274222).
RESULTS
Of 304 studies identified, 46 were eligible for full-text review, and 12 and 18 articles were included for the efficacy and PK analyses, respectively. Of 1830 children included in the efficacy analysis, 82% had favorable outcomes (range, 25%-95%). At World Health Organization-recommended doses, exposures to RIF, pyrazinamide, and ethambutol were lower in children than in adults. Children ≤6 years old have 35% lower areas under the concentration-time curve (AUCs) than older children (mean of 14.4 [95% CI 9.9-18.8] vs 22.0 [13.8-30.1] μg·h/mL) and children with human immunodeficiency virus (HIV) had 35% lower RIF AUCs than HIV-negative children (17.3 [11.4-23.2] vs 26.5 [21.3-31.7] μg·h/mL). Heterogeneity and small sample sizes were major limitations.
CONCLUSIONS
There is large variability in outcomes, with an average of 82% favorable outcomes. Drug exposures are lower in children than in adults. Younger children and/or those with HIV are underexposed to RIF. Standardization of PK pediatric studies and individual patient data analysis with safety assessment are needed to inform optimal dosing.
Topics: Adult; Adolescent; Child; Humans; Antitubercular Agents; Pyrazinamide; Ethambutol; Tuberculosis; Rifampin; Isoniazid; HIV; HIV Infections
PubMed: 36609692
DOI: 10.1093/cid/ciac973 -
Abdominal Radiology (New York) Mar 2023This study aimed to systematically determine the inter-reader reliability of the functional liver imaging score (FLIS) and explore the factors affecting it. (Meta-Analysis)
Meta-Analysis
PURPOSE
This study aimed to systematically determine the inter-reader reliability of the functional liver imaging score (FLIS) and explore the factors affecting it.
METHODS
Original articles reporting the inter-reader reliability of FLIS derived from gadoxetic acid-enhanced magnetic resonance imaging (MRI) were systematically searched in the MEDLINE and EMBASE databases from January 2013 to June 2022. Data synthesis was performed to calculate the meta-analytic pooled estimates of the FLIS and its three subcategories, including enhancement quality score (EnQS), excretion quality score (ExQS), and portal vein sign quality score (PVsQS) using the DerSimonian-Laird random-effects model. To explore any cause of study heterogeneity, we conducted a meta-regression analysis.
RESULTS
Six studies with data from 1419 patients were included. The meta-analytic pooled inter-reader reliability of FLIS was 0.93 (95% confidence interval [CI], 0.88-0.98). That of the three FLIS subcategories were 0.93 (95% CI, 0.85-1.00), 0.95 (95% CI, 0.91-1.00), and 0.90 (95% CI, 0.81-0.99) for EnQS, ExQS, and PVsQS, respectively. The pooled FLIS data was moderately heterogenous, but heterogeneity was not associated with the study methodology, MRI-related factors, and reader experience.
CONCLUSION
The FLIS and its three subcategories showed almost perfect inter-reader reliability. Therefore, FLIS may be a reliable imaging parameter that reflects liver function and outcomes in patients with chronic liver disease. Further studies should be conducted to confirm any factors affecting the inter-reader reliability of FLIS.
Topics: Humans; Contrast Media; Reproducibility of Results; Retrospective Studies; Gadolinium DTPA; Liver; Magnetic Resonance Imaging; Liver Neoplasms
PubMed: 36576517
DOI: 10.1007/s00261-022-03785-x -
The European Respiratory Journal Mar 2023Suboptimal exposure to antituberculosis (anti-TB) drugs has been associated with unfavourable treatment outcomes. We aimed to investigate estimates and determinants of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Suboptimal exposure to antituberculosis (anti-TB) drugs has been associated with unfavourable treatment outcomes. We aimed to investigate estimates and determinants of first-line anti-TB drug pharmacokinetics in children and adolescents at a global level.
METHODS
We systematically searched MEDLINE, Embase and Web of Science (1990-2021) for pharmacokinetic studies of first-line anti-TB drugs in children and adolescents. Individual patient data were obtained from authors of eligible studies. Summary estimates of total/extrapolated area under the plasma concentration-time curve from 0 to 24 h post-dose (AUC) and peak plasma concentration ( ) were assessed with random-effects models, normalised with current World Health Organization-recommended paediatric doses. Determinants of AUC and were assessed with linear mixed-effects models.
RESULTS
Of 55 eligible studies, individual patient data were available for 39 (71%), including 1628 participants from 12 countries. Geometric means of steady-state AUC were summarised for isoniazid (18.7 (95% CI 15.5-22.6) h·mg·L), rifampicin (34.4 (95% CI 29.4-40.3) h·mg·L), pyrazinamide (375.0 (95% CI 339.9-413.7) h·mg·L) and ethambutol (8.0 (95% CI 6.4-10.0) h·mg·L). Our multivariate models indicated that younger age (especially <2 years) and HIV-positive status were associated with lower AUC for all first-line anti-TB drugs, while severe malnutrition was associated with lower AUC for isoniazid and pyrazinamide. -acetyltransferase 2 rapid acetylators had lower isoniazid AUC and slow acetylators had higher isoniazid AUC than intermediate acetylators. Determinants of were generally similar to those for AUC.
CONCLUSIONS
This study provides the most comprehensive estimates of plasma exposures to first-line anti-TB drugs in children and adolescents. Key determinants of drug exposures were identified. These may be relevant for population-specific dose adjustment or individualised therapeutic drug monitoring.
Topics: Child; Adolescent; Humans; Child, Preschool; Antitubercular Agents; Isoniazid; Pyrazinamide; Ethambutol; Rifampin
PubMed: 36328357
DOI: 10.1183/13993003.01596-2022 -
Acta Radiologica (Stockholm, Sweden :... Apr 2023Accurate preoperative diagnosis of post-hepatectomy liver failure (PHLF) is particularly important to improve the prognosis of patients. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Accurate preoperative diagnosis of post-hepatectomy liver failure (PHLF) is particularly important to improve the prognosis of patients.
PURPOSE
To evaluate the predictive value of Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) for post-hepatectomy liver failure.
MATERIAL AND METHODS
A systematic search was performed in the PubMed, Embase, the Cochrane Library, and Web of Science databases to find relevant original articles published up to December 2021. The included studies were assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. The bivariate random-effects model was used to assess the diagnostic authenticity. Meta-regression analyses were performed to analyze the potential heterogeneity.
RESULTS
In total, 13 articles were included. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and the area under the summary receiver operating characteristic curves were 88% (95% confidence interval [CI] = 0.80-0.94), 80% (95% CI = 0.73-0.86), 4.4 (95% CI = 3.3-5.9), 0.14 (95% CI = 0.08-0.25), 31 (95% CI = 17-57), and 0.91 (95% CI = 0.89-0.94), respectively. There was no publication bias and threshold effect in our study.
CONCLUSION
Gd-EOB-DTPA-enhanced MRI is a potentially useful for the prediction of PHLF after major hepatectomy.
Topics: Humans; Liver Neoplasms; Hepatectomy; Contrast Media; Sensitivity and Specificity; Gadolinium DTPA; Magnetic Resonance Imaging; Liver Failure; Liver
PubMed: 36303435
DOI: 10.1177/02841851221134485 -
Academic Radiology Jul 2023The aim of the current study was to investigate whether hypointense hepatocellular carcinoma (HCC) in the hepatobiliary phase (HBP) on gadoxetic acid-enhanced MRI at... (Meta-Analysis)
Meta-Analysis
RATIONALE AND OBJECTIVES
The aim of the current study was to investigate whether hypointense hepatocellular carcinoma (HCC) in the hepatobiliary phase (HBP) on gadoxetic acid-enhanced MRI at pretreatment is a potential prognostic marker for tumor recurrence within 3 years after surgery conducted for a curative purpose (resection or liver transplantation).
MATERIALS AND METHODS
Systematic review was performed in the PubMed, Embase, Cochrane Library, and LILACS databases. Original articles focused on evaluating HCC signal intensity (SI) in HBP, as well as recurrence at least 3 years after surgery were included in the study. Odds ratio (OR) was measured based on the inverse variance method and the random-effects model. The Quality in Prognosis Studies (QUIPS) tool was used to assess the quality of the included articles.
RESULTS
Five studies with 718 patients, in total, were analyzed. The odds ratio of disease recurrence in patients with hypointense HCC in the HBP, within 3 years after surgery, was 3.12 times higher than that observed in patients with hyperintense HCC in the HBP (OR 3.12; 95% CI 1.27-7.68; p = 0.01). Heterogeneity was classified as intermediate (I = 52%). Articles included in the review overall presented a low risk of bias.
CONCLUSION
Hypointense HCC in the HBP on gadoxetic acid-enhanced MRI at pretreatment has increased the likelihood of tumor recurrence in patients subjected to resection or liver transplantation. HCC SI in the HBP is a potential non-invasive imaging biomarker associated with patient prognosis.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Neoplasm Recurrence, Local; Contrast Media; Gadolinium DTPA; Magnetic Resonance Imaging; Retrospective Studies
PubMed: 36253237
DOI: 10.1016/j.acra.2022.09.015 -
European Journal of Pediatrics Jan 2023The diuretic effect of the combined furosemide and aminophylline/theophylline among pediatric patients remains unclear. The primary aim of this systematic review was to... (Review)
Review
UNLABELLED
The diuretic effect of the combined furosemide and aminophylline/theophylline among pediatric patients remains unclear. The primary aim of this systematic review was to examine the clinical diuretic effects (urine output and fluid balance) of co-administration of furosemide and aminophylline/theophylline as compared to furosemide alone in pediatric population. Ovid MEDLINE, CENTRAL, and EMBASE were searched from its inception until March 2022 for observational studies and randomized controlled trials (RCTs) comparing the administration of furosemide versus furosemide and aminophylline/theophylline in pediatric population. Case reports, case series, commentaries, letters to editors, systematic reviews, and meta-analyses were excluded. Five articles with a total sample population of 187 patients were included in this systematic review. As compared to the furosemide alone, our pooled data demonstrated that co-administration of furosemide and aminophylline/theophylline was associated with higher urine output (mean difference: 2.91 [90% CI 1.54 to 4.27], p < 0.0001, I = 90%) and a more negative fluid balance (mean difference - 28.27 [95% CI: - 46.21 to - 10.33], p = 0.002, I = 56%) than those who received furosemide alone.
CONCLUSION
This is the first paper summarizing the evidence of combined use of furosemide with aminophylline/theophylline in pediatric population. Our systematic review demonstrated that the co-administration of furosemide and aminophylline/theophylline could potentially yield better diuretic effects of urine output and negative fluid balance than furosemide alone in pediatric patients with fluid overload. Given the substantial degree of heterogeneity and low level of evidence, future adequately powered trials are warranted to provide evidence regarding the combined use of aminophylline/theophylline and furosemide as diuretic in the pediatric population.
WHAT IS KNOWN
• Fluid overload is associated with poor prognosis for children in the intensive care unit. • The ineffective result of furosemide alone, even at high dose, as diuretic agent for children with diuretic resistant fluid overload in the intensive care unit.
WHAT IS NEW
• This is the first systematic review that compares furosemide alone and co-administration of furosemide and aminophylline/theophylline. • This paper showed potential benefit of co-administration of furosemide and aminophylline/theophylline promoting urine output and negative fluid balance compared to furosemide alone.
Topics: Child; Humans; Diuretics; Theophylline; Aminophylline; Furosemide
PubMed: 36251063
DOI: 10.1007/s00431-022-04655-w -
Odontology Jan 2023This systematic review aims to analyse the available evidence concerning the use of citric acid (CA) in endodontics treatment and to assess its results in terms of... (Review)
Review
This systematic review aims to analyse the available evidence concerning the use of citric acid (CA) in endodontics treatment and to assess its results in terms of different considerations: effect on smear layer removal, influence on sealer bond strength, activation effect by means of sonic or ultrasonic devices, effects on dentine surface, antibacterial activity, and effectiveness boost for regenerative procedures, releasing growth factors from dentin. To evaluate the results of CA as a final irrigant and compare them to other chelating agents. This review followed the PRISMA checklist. An electronic search was conducted in MEDLINE (OVID), Scopus (Elsevier) and the Web of Science (Thomson Reuters) databases. Risk of bias of included studies was evaluated using the modified CONSORT checklist and the PRIRATE checklist 2020 guidelines. 39 studies fulfilled the eligibility criteria to be included in this review: 27 in vitro studies using extracted human teeth, 10 in vitro studies using human dentin disks, and 2 RCT. Citric acid has proven to be effective in smear layer removal, showing better results in coronal and middle root thirds, improving its effect when combined with manual dynamic activation. There is no agreement regarding citric acid effect on sealer adhesion and adaptation to root canal walls due to heterogeneity within studies. Citric acid irrigation can decrease dentine microhardness and cause decalcification and erosion, especially when used before NaOCl. Citric acid has proven to be beneficial in regenerative endodontic procedures due to higher TGF-β1 release.Trial registration: Prospero database CRD42021267055.
Topics: Humans; Citric Acid; Edetic Acid; Smear Layer; Dental Pulp Cavity; Root Canal Preparation; Root Canal Irrigants; Dentin; Microscopy, Electron, Scanning; Sodium Hypochlorite
PubMed: 36220913
DOI: 10.1007/s10266-022-00744-2 -
PloS One 2022Methylxanthine, including caffeine citrate and aminophylline, is the most common pharmacologic treatment for apnea of prematurity. However, due to the lack of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Methylxanthine, including caffeine citrate and aminophylline, is the most common pharmacologic treatment for apnea of prematurity. However, due to the lack of high-quality evidence, there are no clear recommendations or guidelines on how to choose between caffeine and aminophylline.
OBJECTIVE
This meta-analysis aimed to assess the comparative efficacy and safety of caffeine and aminophylline for apnea of prematurity, and provide reliable evidence for clinical medication in the treatment for apnea of prematurity.
METHODS
PubMed, Scopus, Embase, EBSCO, Web of Science, and Cochrane databases were systematically searched from May 1975 to June 2022.
RESULTS
Ten studies including a total of 923 preterm infants were evaluated. Our results showed that there was no significant difference in the effective rate of 1-3days between caffeine and aminophylline (OR 1.05, 95%CI: 0.40-2.74, P = 0.914). However, for side effects such as tachycardia (OR 0.22, 95%CI: 0.13-0.37, P<0.001) and feeding intolerance (OR 0.40, 95%CI: 0.23-0.70, P = 0.001), the incidence rate was lower in the caffeine group compared with the aminophylline group. No significant difference was found in hyperglycemia (OR 0.45, 95%CI: 0.19-1.05, P = 0.064).
CONCLUSION
This meta-analysis reveals that caffeine citrate and aminophylline have similar therapeutic effectiveness on respiratory function, but caffeine has fewer side effects and should be considered first for treatment.
Topics: Aminophylline; Apnea; Caffeine; Citrates; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature; Infant, Premature, Diseases
PubMed: 36121807
DOI: 10.1371/journal.pone.0274882