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Clinical Therapeutics Jun 2022Heavily treatment-experienced (HTE) people with multidrug-resistant HIV-1 have limited treatment options. Treatment with the first-in-class attachment inhibitor...
PURPOSE
Heavily treatment-experienced (HTE) people with multidrug-resistant HIV-1 have limited treatment options. Treatment with the first-in-class attachment inhibitor fostemsavir in addition to optimized background therapy (OBT) resulted in sustained virologic and immunologic responses in HTE participants throughout 96 weeks in the BRIGHTE trial. In the absence of long-term direct comparative evidence between fostemsavir-based and other antiretroviral regimens, this analysis indirectly compares efficacy and safety across relevant available trials, adjusting for demographic and baseline characteristics.
METHODS
A systematic literature review was conducted to identify trials with designs and populations comparable to BRIGHTE. Using matching-adjusted indirect comparison analyses, individual participant data from BRIGHTE were reweighted to create balanced populations across trials, and efficacy and safety outcomes were compared.
FINDINGS
Three comparator trials were identified, 2 of which reflected an optimized therapy without fostemsavir (OBT alone): TMB-301 (ibalizumab and OBT), BENCHMRK-1/-2 (OBT alone), and VIKING-3 (OBT alone). Compared with ibalizumab and OBT (N = 40), fostemsavir and OBT (unadjusted, N = 347; adjusted, N = 236) were associated with numerically higher nonsignificant odds of virologic suppression (odds ratio [OR] = 1.44; 95% CI, 0.74-2.80; P = 0.284) and a similar increase in CD4 cell count of approximately 65 cells/mm from baseline through week 24 (mean difference = 7.05 cells/mm; 95% CI, -60.88 to 74.98 cells/mm; P = 0.834). Compared with OBT from BENCHMRK-1/-2 (N = 237), fostemsavir and OBT (adjusted, N = 126) were associated with significantly higher odds of virologic suppression (OR = 3.26; 95% CI, 2.08-5.11; P < 0.001) and increased CD4 cell count (135.78 cells/mm; 95% CI, 91.93-179.63 cells/mm; P < 0.001) at week 96. Compared with OBT from VIKING-3 (N = 183), fostemsavir and OBT (adjusted, N = 78) were associated with numerically higher odds of virologic suppression (OR = 1.34; 95% CI, 0.78-2.30; P = 0.297) and a modest CD4 cell count increase (26.86 cells/mm; 95% CI, -10.79 to 64.52; P = 0.162) through week 48; however, differences were not significant. All-cause discontinuations and safety comparisons varied across studies.
IMPLICATIONS
Although matching-adjusted indirect comparison analyses have limitations, these results support the use of fostemsavir and OBT as an important treatment option in HTE people with multidrug-resistant HIV-1.
Topics: Anti-HIV Agents; HIV Infections; HIV-1; Humans; Organophosphates; Piperazines; Viral Load
PubMed: 35610081
DOI: 10.1016/j.clinthera.2022.04.007 -
International Archives of Occupational... Jan 2023Human health risk assessments of glyphosate have focused on animal toxicology data for determining neurotoxic potential. Human epidemiological studies have not yet been... (Review)
Review
PURPOSE
Human health risk assessments of glyphosate have focused on animal toxicology data for determining neurotoxic potential. Human epidemiological studies have not yet been systematically reviewed for glyphosate neurotoxicity hazard identification. The objective of this systematic literature review was to summarize the available epidemiology of glyphosate exposure and neurological outcomes in humans.
METHODS
As of December 2021, 25 eligible epidemiological studies of glyphosate exposure and neurological endpoints were identified and assessed for five quality dimensions using guidance from the U.S. Environmental Protection Agency. Studies that assessed personal use of glyphosate were prioritized, whereas those assessing indirect exposure (other than personal use) were rated as low quality, since biomonitoring data indicate that indirect metrics of glyphosate exposure almost always equate to non-detectable glyphosate doses.
RESULTS
Overall, the scientific evidence on glyphosate and neurotoxicity in humans is sparse and methodologically limited, based on nine included epidemiological studies of neurodegenerative outcomes (two high quality), five studies of neurobehavioral outcomes (two high quality), six studies of neurodevelopmental outcomes (none high quality), and five studies of other and mixed neurological outcomes (one high quality). The five high-quality studies showed no association between glyphosate use and risk of depression, Parkinson disease, or peripheral nerve conduction velocity. Results were mixed among the eight moderate-quality studies, which did not demonstrate consistent associations with any neurological endpoints or categories. Low-quality studies were considered uninformative about possible neurotoxic effects due primarily to questionable assessments of indirect exposure.
CONCLUSIONS
No association has been demonstrated between glyphosate and any neurological outcomes in humans. To move the state of science forward, epidemiological studies should focus on scenarios involving direct and frequent use of glyphosate while collecting information on validated health outcomes, concomitant agricultural exposures, and relevant personal characteristics.
Topics: Animals; Humans; Environmental Exposure; Herbicides; Glycine; Risk Assessment; Neurotoxicity Syndromes; Glyphosate
PubMed: 35604441
DOI: 10.1007/s00420-022-01878-0 -
International Journal of Molecular... Apr 2022Glyphosate, a non-selective systemic biocide with broad-spectrum activity, is the most widely used herbicide in the world. It can persist in the environment for days or... (Review)
Review
Glyphosate, a non-selective systemic biocide with broad-spectrum activity, is the most widely used herbicide in the world. It can persist in the environment for days or months, and its intensive and large-scale use can constitute a major environmental and health problem. In this systematic review, we investigate the current state of our knowledge related to the effects of this pesticide on the nervous system of various animal species and humans. The information provided indicates that exposure to glyphosate or its commercial formulations induces several neurotoxic effects. It has been shown that exposure to this pesticide during the early stages of life can seriously affect normal cell development by deregulating some of the signaling pathways involved in this process, leading to alterations in differentiation, neuronal growth, and myelination. Glyphosate also seems to exert a significant toxic effect on neurotransmission and to induce oxidative stress, neuroinflammation and mitochondrial dysfunction, processes that lead to neuronal death due to autophagy, necrosis, or apoptosis, as well as the appearance of behavioral and motor disorders. The doses of glyphosate that produce these neurotoxic effects vary widely but are lower than the limits set by regulatory agencies. Although there are important discrepancies between the analyzed findings, it is unequivocal that exposure to glyphosate produces important alterations in the structure and function of the nervous system of humans, rodents, fish, and invertebrates.
Topics: Animals; Central Nervous System Depressants; Glycine; Herbicides; Neurotoxicity Syndromes; Glyphosate
PubMed: 35562999
DOI: 10.3390/ijms23094605 -
Toxics Sep 2021The incidence of respiratory disease is increasing. In relation to this, in addition to infection, factors associated with working with chemical insecticides are a cause... (Review)
Review
The incidence of respiratory disease is increasing. In relation to this, in addition to infection, factors associated with working with chemical insecticides are a cause for concern. Some of the chemicals involved have been shown to affect the respiratory system, and consequentially workers are at increased risk of conditions such as asthma. However, medical opinion around this area is still controversial; therefore, the objective of this study is to investigate the association between exposure to insecticides and asthma by means of a systematic review of the relevant literature. Relevant literature was identified, and a systematic review was conducted to investigate the association between exposure to insecticides and asthma. A total of five studies (three cross sectional and two cohort) including 45,435 subjects were identified as relevant. The summary odds ratios related to the impact of exposure to specific insecticides on asthma were organophosphates 1.31 (95%CI = 1.17-1.48, I = 27%, = 0.172), carbamates 1.44 (95%CI 1.08-1.92, I = 56.7%, = 0.031) and organochlorines 1.31 (95%CI 1.19-1.64, I = 37.3%, = 0.131). Farmers exposed to certain insecticides may have an increased risk of asthma and asthmatic symptoms, but further research on that issue is urgently needed.
PubMed: 34564379
DOI: 10.3390/toxics9090228 -
Frontiers in Human Neuroscience 2021In recent years, pyrethroids have emerged as a less toxic alternative to eliminate insect pests. However, some animal studies and studies with children show that these...
In recent years, pyrethroids have emerged as a less toxic alternative to eliminate insect pests. However, some animal studies and studies with children show that these pesticides are toxic and lead to neurobehavioral effects similar to other pesticides, such as organophosphates. The purpose of this review was to systematize the epidemiological scientific evidence about the neurobehavioral, neuromotor, and neurocognitive effects in agricultural workers and their children exposed to pyrethroid pesticides. We conducted two searches (with different terms) in PubMed and Scopus databases, including articles in Spanish and English language on the effects of occupational exposure to pyrethroid pesticides associated with neurobehavioral, neuromotor, and neurocognitive functioning of agricultural workers and their children. There were no filters by year, and the search included studies till march 2021. To develop the search, we followed the recommendations contained in the PRISMA guidelines and the PICO strategy. The results show that in 66.6% of the studies reviewed (8 of 12 studies), agricultural workers or their children occupationally exposed to pyrethroid pesticides have a higher risk of presenting difficulties in their neurocognitive, neuromotor, or neurobehavioral performance, mainly associated with attention, processing speed (linked to hand-eye coordination), and motor coordination. There are still few studies that address this issue. However, the quality of most of the research conducted (83% intermediate or high quality) confirms the risk for neurobehavioral health in agricultural workers due to occupational exposure to pyrethroids. More research is required evaluating the exposure to pyrethroids, including biomarkers and validated neurobehavioral and neuromotor tests, in addition to evaluating the effect of simultaneous exposure to other hazardous pesticides. Assuming that the use of pyrethroids is increasing considerably and faster than the scientific evidence, it is suggested as a precautionary principle to regulate, more strictly, the sale of pyrethroids and other pesticides.
PubMed: 34335205
DOI: 10.3389/fnhum.2021.648171 -
International Journal of Environmental... Jul 2021In recent years, the worldwide prevalence of overweight and obesity among adults and children has dramatically increased. The conventional model regarding the onset of... (Review)
Review
In recent years, the worldwide prevalence of overweight and obesity among adults and children has dramatically increased. The conventional model regarding the onset of obesity is based on an imbalance between energy intake and expenditure. However, other possible environmental factors involved, such as the exposure to chemicals like pesticides, cannot be discarded. These compounds could act as endocrine-disrupting chemicals (EDC) that may interfere with hormone activity related to several mechanisms involved in body weight control. The main objective of this study was to systematically review the data provided in the scientific literature for a possible association between prenatal and postnatal exposure to pesticides and obesity in offspring. A total of 25 human and 9 animal studies were analyzed. The prenatal, perinatal, and postnatal exposure to organophosphate, organochlorine, pyrethroid, neonicotinoid, and carbamate, as well as a combined pesticide exposure was reviewed. This systematic review reveals that the effects of pesticide exposure on body weight are mostly inconclusive, finding conflicting results in both humans and experimental animals. The outcomes reviewed are dependent on many factors, including dosage and route of administration, species, sex, and treatment duration. More research is needed to effectively evaluate the impact of the combined effects of different pesticides on human health.
Topics: Adult; Child; Environmental Exposure; Female; Humans; Neonicotinoids; Obesity; Organophosphates; Pesticides; Pregnancy; Pyrethrins
PubMed: 34281107
DOI: 10.3390/ijerph18137170 -
International Journal of Environmental... May 2021Autism spectrum disorder (ASD) is a complex set of neurodevelopmental pathologies characterized by impoverished social and communicative abilities and stereotyped... (Review)
Review
Autism spectrum disorder (ASD) is a complex set of neurodevelopmental pathologies characterized by impoverished social and communicative abilities and stereotyped behaviors. Although its genetic basis is unquestionable, the involvement of environmental factors such as exposure to pesticides has also been proposed. Despite the systematic analyses of this relationship in humans, there are no specific reviews including both human and preclinical models. The present systematic review summarizes, analyzes, and discusses recent advances in preclinical and epidemiological studies. We included 45 human and 16 preclinical studies. These studies focused on Organophosphates (OP), Organochlorine (OC), Pyrethroid (PT), Neonicotinoid (NN), Carbamate (CM), and mixed exposures. Preclinical studies, where the OP Chlorpyrifos (CPF) compound is the one most studied, pointed to an association between gestational exposure and increased ASD-like behaviors, although the data are inconclusive with regard to other ages or pesticides. Studies in humans focused on prenatal exposure to OP and OC agents, and report cognitive and behavioral alterations related to ASD symptomatology. The results of both suggest that gestational exposure to certain OP agents could be linked to the clinical signs of ASD. Future experimental studies should focus on extending the analysis of ASD-like behaviors in preclinical models and include exposure patterns similar to those observed in human studies.
Topics: Autism Spectrum Disorder; Chlorpyrifos; Female; Humans; Pesticides; Pregnancy; Prenatal Exposure Delayed Effects; Pyrethrins
PubMed: 34068255
DOI: 10.3390/ijerph18105190 -
Ciencia & Saude Coletiva Aug 2020Malathion has been widely used worldwide in arbovirus control programs. In 2015, it was classified by the International Agency for Research on Cancer (IARC) as a...
Malathion has been widely used worldwide in arbovirus control programs. In 2015, it was classified by the International Agency for Research on Cancer (IARC) as a probable carcinogen to humans. This work aimed to systematize the evidence of the carcinogenic and mutagenic effects associated with the exposure of malathion and its analogs, malaoxon and isomalathion. The search was carried out in Toxline, PubMed and Scopus databases for original papers published from 1983 to 2015. In all, 73 papers were selected from a total of 273 eligible papers. The results of in vitro and in vivo studies showed mainly genetic and chromosomal damages caused by malathion. The epidemiological studies evidenced significant positive associations for thyroid, breast, and ovarian cancers in menopausal women. This evidence of the carcinogenic effect of malathion should be considered before its use in arbovirus control programs.
Topics: Female; Humans; Malathion; Mutagens
PubMed: 32785560
DOI: 10.1590/1413-81232020258.10672018 -
Environmental Research Aug 2020A growing body of evidences suggests an association between early exposure to organophosphates (OPs), organochlorines (OCs), pyrethroids or carbamates and autism...
Pesticides used in Europe and autism spectrum disorder risk: can novel exposure hypotheses be formulated beyond organophosphates, organochlorines, pyrethroids and carbamates? - A systematic review.
BACKGROUND
A growing body of evidences suggests an association between early exposure to organophosphates (OPs), organochlorines (OCs), pyrethroids or carbamates and autism spectrum disorder (ASD). However, there are limited data about the other pesticide groups, especially in Europe.
OBJECTIVES
Based on a systematic review, we aimed to assess the influence of neuro- and thyrotoxic agricultural and domestic pesticides (other than OPs, OCs, pyrethroids and carbamates) authorized in Europe on risk of ASD in children or ASD behavioral phenotypes in rodents.
METHODS
Pesticides were initially identified in the Hazardous Substances Data Bank. 20 currently used (10 pesticide groups) were retained based on the higher exposure potential. Epidemiological (children) and in vivo (rodents) studies were identified through PubMed, Web of Science and TOXLINE, without restriction of publication date or country (last update: November 2019). The risk of bias and level of evidence were also assessed. This systematic review is registered at the International Prospective Register of Systematic Reviews (PROSPERO, registration number CRD42019145384).
RESULTS
In total, two epidemiological and 15 in vivo studies were retained, focusing on the azole, neonicotinoid, phenylpyrazole and phosphonoglycine pesticide groups. No study was conducted in Europe. Glyphosate, imidacloprid, clothianidin, myclobutanil, acetamiprid, tebuconazole, thiabendazole and fipronil, globally reported an association with an increased risk of ASD in children and/or ASD behavioral phenotypes in rodents. In children, glyphosate and myclobutanil showed a "moderate level of evidence" in their association with ASD, whereas imidacloprid showed an "inadequate level of evidence". In rodents, clothianidin, imidacloprid and glyphosate showed a "high level of evidence" in their association with altered behavioral, learning and memory skills.
CONCLUSION
In the framework of environmental risk factors of ASD, novel hypotheses can be formulated about early exposure to eight pesticides. Glyphosate presented the most salient level of evidence. Given their neuro- and thyrotoxic properties, additional studies are needed for the 12 other pesticides not yet studied as potential ASD risk factors according to our inclusion criteria.
Topics: Autism Spectrum Disorder; Carbamates; Child; Europe; Humans; Organophosphates; Pesticides; Pyrethrins
PubMed: 32460093
DOI: 10.1016/j.envres.2020.109646 -
Revista Brasileira de Epidemiologia =... 2020To update findings of observational analytical studies on the association between occupational exposure to organophosphates and hematologic malignancies.
OBJECTIVE
To update findings of observational analytical studies on the association between occupational exposure to organophosphates and hematologic malignancies.
METHODOLOGY
Systematic literature review, including cohort and case-control studies, without limitation of publication time, in Portuguese and English. The articles were traced from June 2017 to July 2019 in PubMed, MEDLINE, LILACS, Web of Science, and Scopus databases. The qualitative bias risk assessment was performed using the Newcastle-Ottawa Scale and the Downs and Black Checklist. Results were presented according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA).
RESULTS
Seventeen studies evaluated as good/high methodological quality were eligible. Exposure to diazinon (1 cohort), phonophos (1 cohort), dichlorvos, crotoxiphos and famphur (1 case control) was associated with leukemia, while exposure to organophosphate was associated to lymphomas (6 case control); the risk of non-Hodgkin's lymphoma was higher in those exposed to diazinon (1 control case) and malathion (3 control case) than non-exposed ones. Multiple myeloma occurred more commonly in organophosphate exposed than in non-exposed individuals (1 case-control).
CONCLUSION
Occupational exposure to organophosphates increases the risk of hematologic malignancies, especially among individuals with longer exposure periods. Worker monitoring and exposure control measures are recommended.
Topics: Hematologic Neoplasms; Humans; Occupational Exposure; Organophosphate Poisoning; Pesticides; Risk Assessment; Risk Factors; Time Factors
PubMed: 32401913
DOI: 10.1590/1980-549720200022