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Haematologica Apr 20246-mercaptopurine (6-MP) serves as the backbone in the maintenance regimens of acute lymphoblastic leukemia (ALL). We aimed to evaluate the influence of NUDT15 gene... (Meta-Analysis)
Meta-Analysis
Association of gene polymorphism with adverse reaction, treatment efficacy, and dose of 6-mercaptopurine in patients with acute lymphoblastic leukemia: a systematic review and meta-analysis.
6-mercaptopurine (6-MP) serves as the backbone in the maintenance regimens of acute lymphoblastic leukemia (ALL). We aimed to evaluate the influence of NUDT15 gene polymorphism on the risk of myelosupression, hepatotoxicity and interruption of 6-MP, as well as treatment efficacy and dose of 6-MP in ALL patients. A total of 24 studies with 3,374 patients were included in this meta-analysis. We found 9-fold higher risk of 6-MP induced leukopenia (odds ratio [OR] =9.00, 95% confidence interval [CI]: 3.73-21.74) and 2.5-fold higher risk of 6-MP-induced neutropenia (OR=2.52, 95% CI: 1.72-3.69) for NUDT15 c.415C>T variant carriers in the dominant model. Moreover, we found that the dose intensity of 6-MP in ALL patients with one NUDT15 c.415C>T variant alleles (CT) was 19% less than that in wild-type patients (CC) (mean differences: 19.43%, 95% CI: -25.36 to -13.51). The tolerable dose intensity of 6-MP in NUDT15 c.415C>T homozygote variant (TT) and heterozygote variant (CT) carriers was 49% and 15% less than that in wild-type patients, respectively. The NUDT15 c.415C>T variant group (CT+TT) had seven times (OR=6.98, 95% CI: 2.83-17.22) higher risk of developing 6-MP intolerance than the CC group. However, NUDT15 c.415C>T polymorphism did not appear significantly associated with hepatotoxicity, treatment interruption or relapse incidence. We concluded that NUDT15 c.415C>T was a good predictor for 6-MP-induced myelosuppression in ALL patients. The dose intensity of 6-MP in ALL patients with NUDT15 c.415C>T variants was significantly lower than that in wild-type patients. This research provided a basis for further investigation into relations between NUDT15 gene and adverse reaction, treatment efficacy and dose intensity of 6-MP.
Topics: Humans; Mercaptopurine; Pyrophosphatases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Polymorphism, Genetic; Neutropenia; Treatment Outcome; Chemical and Drug Induced Liver Injury
PubMed: 37794799
DOI: 10.3324/haematol.2023.282761 -
Forensic Science International Nov 2023Dog bites pose a significant global public health issue and are the most common type of injury caused by animals. While most dog bites result in minor harm, they can... (Review)
Review
Dog bites pose a significant global public health issue and are the most common type of injury caused by animals. While most dog bites result in minor harm, they can also lead to severe or even fatal consequences. In cases involving serious injury or death, forensic pathologists investigate various aspects, including the crime scene, the injuries sustained by the victim, and the characteristics of the dog suspected to have caused the bite. The aim of this study is to provide a systematic review of the literature on the medical-legal implications of dog bites in forensic practice, in order to recognize the dog bite victim features, the injuries and their consequences related to, and to identify the offending dogs. The literature search was performed using PubMed, Scopus and Web of Science from January 1980 to March 2023. Eligible studies have investigated issues of interest to forensic medicine about dog bites to humans. A total of 116 studies met the inclusion criteria and were included in the review and they were organized and discussed by issue of interest (biting dog features, dog bite victim features, anatomical distribution of dog bites, injuries related to dog bites, cause of death, bite features, dog identification and post-mortem dog depredation). The findings of this systematic review highlight the importance of bite mark analysis in reconstructing the events leading to the attack and identifying the dog responsible. In medical forensic evaluations of dog bite cases, a multidisciplinary approach is crucial. This approach involves thorough analysis of the crime scene, identification of risk factors, examination of dog characteristics, and assessment of the victim's injuries. By combining expertise from both human and veterinary forensic fields, a comprehensive understanding can be achieved in dog bite cases.
Topics: Humans; Dogs; Animals; Bites and Stings; Forensic Medicine; Crime; Risk Factors; Autopsy
PubMed: 37783138
DOI: 10.1016/j.forsciint.2023.111849 -
Toxins Sep 2023The aim of this systematic review is to provide an update on the occurrence and co-occurrence of selected non-regulated mycotoxins and provide an overview of current... (Review)
Review
The aim of this systematic review is to provide an update on the occurrence and co-occurrence of selected non-regulated mycotoxins and provide an overview of current regulations. Fifteen non-regulated mycotoxins were found in 19 food categories worldwide. On top of that, 38 different combinations of non-regulated mycotoxins were found, with mixtures varying from binary combinations up to 12 mycotoxins. Taking into consideration the amount of evidence regarding the prevalence and co-occurrence of non-regulated mycotoxins, future steps should be taken considering continuous monitoring, scientific exchange, and generation of high-quality data. To enhance data quality, guidelines outlining the minimum quality criteria for both occurrence data and metadata are needed. By doing so, we can effectively address concerns related to the toxicity of non-regulated mycotoxins. Furthermore, obtaining more data concerning the co-occurrence of both regulated and non-regulated mycotoxins could aid in supporting multiple chemical risk assessment methodologies. Implementing these steps could bolster food safety measures, promote evidence-based regulations, and ultimately safeguard public health from the potential adverse effects of non-regulated mycotoxins.
Topics: Data Accuracy; Fenbendazole; Food; Food Safety; Mycotoxins
PubMed: 37756008
DOI: 10.3390/toxins15090583 -
Brain Research Bulletin Oct 2023Gait analysis could be used in animal models as an indicator of sensory ataxia due to chemotherapy-induced peripheral neurotoxicity (CIPN). Over the years, gait analysis... (Review)
Review
Gait analysis could be used in animal models as an indicator of sensory ataxia due to chemotherapy-induced peripheral neurotoxicity (CIPN). Over the years, gait analysis in in vivo studies has evolved from simple observations carried out by a trained operator to computerised systems with machine learning that allow the quantification of any variable of interest and the establishment of algorithms for behavioural classification. However, there is not a consensus on gait analysis use in CIPN animal models; therefore, we carried out a systematic review. Of 987 potentially relevant studies, 14 were included, in which different methods were analysed (observation, footprint and CatWalk™). We presented the state-of-the-art of possible approaches to analyse sensory ataxia in rodent models, addressing advantages and disadvantages of different methods available. Semi-automated methods may be of interest when preventive or therapeutic strategies are evaluated, also considering their methodological simplicity and automaticity; up to now, only CatWalk™ analysis has been tested. Future studies should expect that CIPN-affected animals tend to reduce hind paw support due to pain, allodynia or loss of sensation, and an increase in swing phase could or should be observed. Few available studies documented these impairments at the last time point, and only appeared later on respect to other earlier signs of CIPN (such as altered neurophysiological findings). For that reason, gait impairment could be interpreted as late repercussions of loss of sensory.
Topics: Animals; Peripheral Nervous System Diseases; Gait Analysis; Rodentia; Neurotoxicity Syndromes; Antineoplastic Agents; Ataxia
PubMed: 37748696
DOI: 10.1016/j.brainresbull.2023.110769 -
Eastern Mediterranean Health Journal =... Aug 2023
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Cureus Aug 2023Calcium channel blocker poisoning is one of the most common poisonings encountered which presents with life-threatening complications. However, there is no unified... (Review)
Review
Calcium channel blocker poisoning is one of the most common poisonings encountered which presents with life-threatening complications. However, there is no unified approach for treating these patients in the existing literature. This study aimed to assess the effects of different treatment modalities used in calcium channel blocker poisoning, as reported by previous studies. The primary outcomes studied were mortality and hemodynamic parameters after treatment. The secondary outcomes were the length of hospital stay, length of intensive care unit stay, duration of vasopressor use, functional outcomes, and serum calcium channel blocker concentrations. A thorough literature search was performed through Ovid, PubMed, Cochrane Library, and Google Scholar from January 2014 to December 31, 2022, to identify all studies analyzing the effects of the treatment of calcium channel blocker poisoning on the desired outcomes. Two reviewers reviewed 607 published articles from January 2014 to December 2022 to identify studies analyzing the effects of the treatment of calcium channel blocker poisoning on desired outcomes. In this review, 18 case reports, one case series, and one cohort study were included. Most patients were treated with an injection of calcium gluconate or calcium chloride. The use of calcium along with dopamine and norepinephrine was found to have lower mortality rates. A few patients were also treated with injection atropine for bradycardia. High-dose insulin therapy was used in 14 patients, of whom two did not survive. In the cohort study, 66 calcium channel blocker toxicity patients were included. These patients were treated with high-dose insulin therapy. A total of 11 patients with calcium channel blocker toxicity succumbed. Although it was found to be associated with improved hemodynamic parameters and lower mortality, side effects such as hypokalemia and hypoglycemia were noted. Intravenous lipid emulsion therapy (administered to eight patients), extracorporeal life support (used in three patients with refractory shock or cardiac arrest), injection glucagon, methylene blue, albumin infusion, and terlipressin were associated with a lower mortality rate as well as improvement in hemodynamic parameters. None of the case reports provided any information on end-organ damage on long-term follow-up.
PubMed: 37664357
DOI: 10.7759/cureus.42854 -
BMC Psychiatry Aug 2023Adolescents and adults with attention-deficit/hyperactivity disorder (ADHD) are at increased risk of suicidal spectrum behaviors (SSBs). However, there is limited...
INTRODUCTION
Adolescents and adults with attention-deficit/hyperactivity disorder (ADHD) are at increased risk of suicidal spectrum behaviors (SSBs). However, there is limited knowledge about risk factors triggering SSBs in this group of people.
OBJECTIVE
To explore published literature concerning factors that may increase the risk of SSBs in adults and adolescents with ADHD.
METHODS
A systematic literature search following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted on 22 of February 2022 using the Ovid MEDLINE and Web of Science databases. Three categories of search terms were used: (1) self-harm, self-injury, self-mutilation, suicide, self-poisoning; (2) adults, adolescents; and (3) attention-deficit hyperactivity disorder/ADHD. Studies with data concerning mediating factors of SSBs in relation to a clinical diagnosis of ADHD in participants above 16 years of age were included.
RESULTS
The literature search identified 604 articles, of which 40 were included in the final study selection. Factors found to increase the likelihood of SSBs included ADHD symptom severity and persistence, female gender, family history of ADHD, childhood and parental influences, and social functioning. Even when adjusting for psychiatric comorbidities, most studies showed that adults and adolescents with ADHD have an elevated risk of SSBs.
CONCLUSION
This systematic review has documented that several demographic and clinical features are associated with an increased risk of SSBs in adolescents and adults with ADHD. Notably, ADHD emerges as an independent risk factor for SSBs. This information ought to have clinical implications in terms of screening and suicide prevention strategies. Further longitudinal studies are needed to investigate the outcome of preventive strategies in individuals along the full spectrum of ADHD symptom severity.
Topics: Humans; Adolescent; Adult; Female; Child; Suicidal Ideation; Attention Deficit Disorder with Hyperactivity; Suicide; Self-Injurious Behavior; Risk Factors
PubMed: 37605105
DOI: 10.1186/s12888-023-05099-8 -
PLoS Neglected Tropical Diseases Aug 2023Transmission models have a long history in the study of mosquito-borne disease dynamics. The mosquito biting rate (MBR) is an important parameter in these models,...
BACKGROUND
Transmission models have a long history in the study of mosquito-borne disease dynamics. The mosquito biting rate (MBR) is an important parameter in these models, however, estimating its value empirically is complex. Modeling studies obtain biting rate values from various types of studies, each of them having its strengths and limitations. Thus, understanding these study designs and the factors that contribute to MBR estimates and their variability is an important step towards standardizing these estimates. We do this for an important arbovirus vector Aedes aegypti.
METHODOLOGY/PRINCIPAL FINDINGS
We perform a systematic review using search terms such as 'biting rate' and 'biting frequency' combined with 'Aedes aegypti' ('Ae. aegypti' or 'A. aegypti'). We screened 3,201 articles from PubMed and ProQuest databases, of which 21 met our inclusion criteria. Two broader types of studies are identified: human landing catch (HLC) studies and multiple feeding studies. We analyze the biting rate data provided as well as the methodologies used in these studies to characterize the variability of these estimates across temporal, spatial, and environmental factors and to identify the strengths and limitations of existing methodologies. Based on these analyses, we present two approaches to estimate population mean per mosquito biting rate: one that combines studies estimating the number of bites taken per gonotrophic cycle and the gonotrophic cycle duration, and a second that uses data from histological studies. Based on one histological study dataset, we estimate biting rates of Ae. aegypti (0.41 and 0.35 bite/mosquito-day in Thailand and Puerto Rico, respectively).
CONCLUSIONS/SIGNIFICANCE
Our review reinforces the importance of engaging with vector biology when using mosquito biting rate data in transmission modeling studies. For Ae. aegypti, this includes understanding the variation of the gonotrophic cycle duration and the number of bites per gonotrophic cycle, as well as recognizing the potential for spatial and temporal variability. To address these variabilities, we advocate for site-specific data and the development of a standardized approach to estimate the biting rate.
Topics: Animals; Humans; Mosquito Vectors; Aedes; Insect Bites and Stings; Thailand; Feeding Behavior
PubMed: 37552669
DOI: 10.1371/journal.pntd.0010831 -
JAMA Network Open Aug 2023Concerns that take-home naloxone (THN) training may lead to riskier drug use (as a form of overdose risk compensation) remain a substantial barrier to training...
IMPORTANCE
Concerns that take-home naloxone (THN) training may lead to riskier drug use (as a form of overdose risk compensation) remain a substantial barrier to training implementation. However, there was limited good-quality evidence in a systematic review of the association between THN access and subsequent risk compensation behaviors.
OBJECTIVE
To assess whether THN training is associated with changes in overdose risk behaviors, indexed through injecting frequency, in a cohort of people who inject drugs.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study used prospectively collected self-reported behavioral data before and after THN training of participants in The Melbourne Injecting Drug User Cohort Study (SuperMIX). Annual interviews were conducted in and around Melbourne, Victoria, Australia, from 2008 to 2021. SuperMIX participants were adults who regularly injected heroin or methamphetamine in the 6 months preceding their baseline interview. The current study included only people who inject drugs who reported THN training and had participated in at least 1 interview before THN training.
EXPOSURE
In 2017, the SuperMIX baseline or follow-up survey began asking participants if and when they had received THN training. The first THN training date that was recorded was included as the exposure variable. Subsequent participant interviews were excluded from analysis.
MAIN OUTCOMES AND MEASURES
Injecting frequency was the primary outcome and was used as an indicator of overdose risk. Secondary outcomes were opioid injecting frequency, benzodiazepine use frequency, and the proportion of the time drugs were used alone. Fixed-effects generalized linear (Poisson) multilevel modeling was used to estimate the association between THN training and the primary and secondary outcomes. Time-varying covariates included housing status, income, time in study, recent opioid overdose, recent drug treatment, and needle and syringe coverage. Findings were expressed as incidence rate ratios (IRRs) with 95% CIs.
RESULTS
There were 1328 participants (mean [SD] age, 32.4 [9.0] years; 893 men [67.2%]) who completed a baseline interview in the SuperMIX cohort, and 965 participants completed either a baseline or follow-up interview in or after 2017. Of these 965 participants, 390 (40.4%) reported THN training. A total of 189 people who inject drugs had pretraining participant interviews with data on injecting frequency and were included in the final analysis (mean [SD] number of interviews over the study period, 6.2 [2.2]). In fixed-effects regression analyses adjusted for covariates, there was no change in the frequency of injecting (IRR, 0.91; 95% CI, 0.69-1.20; P = .51), opioid injecting (IRR, 0.95; 95% CI, 0.74-1.23; P = .71), benzodiazepine use (IRR, 0.96; 95% CI, 0.69-1.33; P = .80), or the proportion of reported time of using drugs alone (IRR, 1.04; 95% CI, 0.86-1.26; P = .67) before and after THN training.
CONCLUSIONS AND RELEVANCE
This cohort study of people who inject drugs found no evidence of an increase in injecting frequency, along with other markers of overdose risk, after THN training and supply. The findings suggest that THN training should not be withheld because of concerns about risk compensation and that advocacy for availability and uptake of THN is required to address unprecedented opioid-associated mortality.
Topics: Male; Adult; Humans; Naloxone; Narcotic Antagonists; Analgesics, Opioid; Cohort Studies; Drug Overdose; Victoria
PubMed: 37540514
DOI: 10.1001/jamanetworkopen.2023.27319 -
Skin Health and Disease Aug 2023Cutaneous and systemic signs of acute and chronic arsenic poisoning may be vague. Thus, an awareness of these signs is crucial to prevent late or missed diagnoses. This... (Review)
Review
Cutaneous and systemic signs of acute and chronic arsenic poisoning may be vague. Thus, an awareness of these signs is crucial to prevent late or missed diagnoses. This is especially true in non-endemic countries where individuals may present decades after exposure, or may still be ingesting arsenic via a non-classical exposure. Existing literature emphasizes several well-known cutaneous presentations of arsenic toxicity while ignoring the complete clinical spectrum, including several rare tumours of relevance to the dermatologist. This study aims to review the existing literature on dermatological presentations of arsenic toxicity and their management in adults.
PubMed: 37538334
DOI: 10.1002/ski2.231