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Systematic Reviews May 2020Environmental factors such as pollution, pesticide exposure and socio-demographic location have been implicated as a pressure capable of altering genetic make-up....
Environmental factors such as pollution, pesticide exposure and socio-demographic location have been implicated as a pressure capable of altering genetic make-up. Altered genetic sequence of genes encoding enzymes may result in single nucleotide polymorphism (SNP). Of peculiar interest is the genetic variance on the paraoxonase-1 gene induced by pre- and postnatal exposure to pesticides. SNP have been reported on the paraoxonase-1 gene and post-xenobiotic exposure and are presumed to alter gene sequence and ultimately enzymatic activity. The altered enzymatic activity may facilitate neurodevelopment disorders. Autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD) are among the neurodevelopment disorders of which prevalence is concurrently associated with increasing environmental xenobiotic exposure. The variance on xenobiotic metabolising genes is associated with altered neurodevelopment outcome and ultimately altered neurobehavioural outcome. Prime interests of this systematic review were to establish an understanding of the sequences on the paraoxonase-1 gene associated with adverse neurobehavioural outcome. An in-depth literature search was conducted using the term combination "pesticide exposure, pre- and postnatal exposure, organophosphates/organophosphorus, single nucleotide polymorphism, paraoxonase-1 (PON-1), neurodevelopment/neurobehavioural outcome in child/infant". Articles published from the year 2000 to 2018 were considered for review. The result showed that variance on the PON1-108 and 192 alleles could be implicated in the development of altered neurobehavioural outcomes.
Topics: Aryldialkylphosphatase; Child; Environmental Exposure; Humans; Organophosphates; Pesticides; Polymorphism, Single Nucleotide
PubMed: 32386510
DOI: 10.1186/s13643-020-01330-9 -
Cureus Mar 2020Introduction The benefits of atropine in the treatment of acute organophosphate (OP) poisoning has been well established, while that of oximes is still uncertain....
Introduction The benefits of atropine in the treatment of acute organophosphate (OP) poisoning has been well established, while that of oximes is still uncertain. Pralidoxime is the most often used oxime worldwide. In vitro experiments have consistently shown that oximes are effective reactivators of human acetylcholinesterase enzyme, inhibited by OP compounds. However, the clinical benefit of pralidoxime is still unclear. A recent meta-analysis has found that pralidoxime provides no significant improvement in outcome and rather may cause harm while increasing the economic burden in low-income communities where its use is the most prevalent. Objectives This study aimed to provide an updated evaluation of the efficacy of pralidoxime in addition to atropine alone in the treatment of patients with acute OP poisoning in terms of mortality, need for ventilator support, and the incidence of intermediate syndrome. The intermediate syndrome is a clinical syndrome that occurs 24 to 96 hours after the ingestion of an OP compound and is characterized by prominent weakness of neck flexors, muscles of respiration, and proximal limb muscles. Materials and methods We searched MEDLINE, EMBASE, CENTRAL, and ClinicalTrials.gov databases until January 2019 for randomized controlled trials (RCTs) in the English language that evaluated the use of pralidoxime in individuals of any age, gender or nationality presenting with an alleged history of OP intake. The primary outcome was mortality. Secondary outcomes were the need for ventilator support and the incidence of intermediate syndrome. The risk of bias in included studies was assessed using the tool recommended by the Cochrane Handbook of Systematic Review of Interventions. Treatment/control differences in these outcomes across included studies were combined using risk ratios (RR). Results Six randomized controlled trials (n = 646) fulfilled the inclusion criteria, including one further trial missed from the most recent systematic review. The risk of bias varied across studies, with Eddleston 2009 being of the lowest risk and Cherian 2005 being of high risk. The risk of mortality (RR = 1.53, 95% confidence interval (CI) 0.97 to 2.41, P = 0.07) and the need for ventilator support (RR = 1.29, 95% CI 0.97 to 1.71, P = 0.08) were not significantly different between the pralidoxime and the control group. There was a significant increase in the incidence of intermediate syndrome in the pralidoxime group (RR = 1.63; 95% CI 1.01 to 2.62, P = 0.04). Conclusions Based on our meta-analysis of the available RCTs, pralidoxime was not shown to be beneficial in patients with acute OP poisoning. Our findings are consistent with the other literature.
PubMed: 32257715
DOI: 10.7759/cureus.7174 -
La Medicina Del Lavoro Feb 2020We carried out a systematic review and meta-analysis of epidemiologic studies on the association between occupational exposure to glyphosate and risk of non-Hodgkin... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
We carried out a systematic review and meta-analysis of epidemiologic studies on the association between occupational exposure to glyphosate and risk of non-Hodgkin lymphoma (NHL) and multiple myeloma (MM).
METHODS
We conducted a systematic search of the literature, and identified 18 relevant publications, from which we extracted results from seven non-overlapping studies of NHL and three of MM. We performed random-effects meta-analyses for ever-exposure to glyphosate, dose-response, and risk of specific NHL subtypes.
RESULTS
The meta-relative risk (RR) of NHL was 1.03 (95% confidence interval [CI] 0.86-1.21), that of MM was 1.04 (95% CI 0.67-1.41). The meta-RR of NHL for highest category of exposure was 1.49 (95% CI 0.37-2.61; 3 studies). The meta-RR for diffuse large B-cell lymphoma (DLBCL) was 1.31 (95% CI 0.93-1.75); that for follicular lymphoma was 0.82 (95% CI 0.93-1.70), and that for chronic lymphocytic leukemia was 0.85 (95% CI 0.20-1.49). There was indication of publication bias for studies on NHL.
CONCLUSIONS
Our meta-analysis provided no overall evidence of an increased risk for both NHL and MM in subjects occupationally exposed to glyphosate. In secondary analyses we detected a small increase in risk for the category with highest level of exposure as well as for DLBCL. The evidence of publication bias suggests caution in the interpretation of the results.
Topics: Glycine; Humans; Lymphoma, Non-Hodgkin; Multiple Myeloma; Occupational Exposure; Risk Factors; Glyphosate
PubMed: 32096774
DOI: 10.23749/mdl.v111i1.8967 -
Mutation Research. Reviews in Mutation... 2019Glyphosate is the most widely used broad-spectrum systemic herbicide in the world. Recent evaluations of the carcinogenic potential of glyphosate-based herbicides (GBHs)... (Meta-Analysis)
Meta-Analysis
Glyphosate is the most widely used broad-spectrum systemic herbicide in the world. Recent evaluations of the carcinogenic potential of glyphosate-based herbicides (GBHs) by various regional, national, and international agencies have engendered controversy. We investigated whether there was an association between high cumulative exposures to GBHs and increased risk of non-Hodgkin lymphoma (NHL) in humans. We conducted a new meta-analysis that includes the most recent update of the Agricultural Health Study (AHS) cohort published in 2018 along with five case-control studies. Using the highest exposure groups when available in each study, we report the overall meta-relative risk (meta-RR) of NHL in GBH-exposed individuals was increased by 41% (meta-RR = 1.41, 95% confidence interval, CI: 1.13-1.75). For comparison, we also performed a secondary meta-analysis using high-exposure groups with the earlier AHS (2005), and we calculated a meta-RR for NHL of 1.45 (95% CI: 1.11-1.91), which was higher than the meta-RRs reported previously. Multiple sensitivity tests conducted to assess the validity of our findings did not reveal meaningful differences from our primary estimated meta-RR. To contextualize our findings of an increased NHL risk in individuals with high GBH exposure, we reviewed publicly available animal and mechanistic studies related to lymphoma. We documented further support from studies of malignant lymphoma incidence in mice treated with pure glyphosate, as well as potential links between glyphosate / GBH exposure and immunosuppression, endocrine disruption, and genetic alterations that are commonly associated with NHL or lymphomagenesis. Overall, in accordance with findings from experimental animal and mechanistic studies, our current meta-analysis of human epidemiological studies suggests a compelling link between exposures to GBHs and increased risk for NHL.
Topics: Carcinogens; Glycine; Herbicides; Humans; Lymphoma, Non-Hodgkin; Risk; Glyphosate
PubMed: 31342895
DOI: 10.1016/j.mrrev.2019.02.001 -
Frontiers in Behavioral Neuroscience 2019Impulsive and compulsive traits represent a variety of maladaptive behaviors defined by the difficulties to stop an improper response and the control of a repeated...
Impulsive and compulsive traits represent a variety of maladaptive behaviors defined by the difficulties to stop an improper response and the control of a repeated behavioral pattern without sensitivity to changing contingencies, respectively. Otherwise, human beings are continuously exposed to plenty neurotoxicological agents which have been systematically linked to attentional, learning, and memory dysfunctions, both preclinical and clinical studies. Interestingly, the link between both impulsive and compulsive behaviors and the exposure to the most important xenobiotic compounds have been extensively developed; although the information has been rarely summarized. For this, the present systematic review schedule and analyze in depth the most important works relating different subtypes of the above-mentioned behaviors with 4 of the most important xenobiotic compounds: Lead (Pb), Methylmercury (MeHg), Polychlorinated biphenyls (PCB), and Organophosphates (OP) in both preclinical and clinical models. Systematic search strategy on PubMed databases was developed, and the most important information was structured both in text and in separate tables based on rigorous methodological quality assessment. For Lead, Methylmercury, Polychlorinated biphenyls and organophosphates, a total of 44 (31 preclinical), 34 (21), 38 (23), and 30 (17) studies were accepted for systematic synthesis, respectively. All the compounds showed an important empirical support on their role in the modulation of impulsive and, in lesser degree, compulsive traits, stronger and more solid in animal models with inconclusive results in humans in some cases (i.e., MeHg). However, preclinical and clinical studies have systematically focused on different subtypes of the above-mentioned behaviors, as well as impulsive choice or habit conformations have been rarely studied. The strong empirical support in preclinical studies contrasts with the lack of connection between preclinical and clinical models, as well as the different methodologies used. Further research should be focused on dissipate these differences as well as deeply study impulsive choice, decision making, risk taking, and cognitive flexibility, both in experimental animals and humans.
PubMed: 31333425
DOI: 10.3389/fnbeh.2019.00139 -
Journal of the American Academy of... May 2019Many drugs have been used to treat scabies, but it is unclear which of them is the most efficacious. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Many drugs have been used to treat scabies, but it is unclear which of them is the most efficacious.
OBJECTIVE
To evaluate the comparative efficacy and safety of antiscabietic agents.
METHODS
A systematic review of randomized controlled trials was conducted. Direct and network meta-analyses were applied to 13 antiscabietic agents on 3 outcomes (cure, persistent itching, and adverse events). Their probability of having highest efficacy and safety was estimated and ranked.
RESULTS
A network meta-analysis of 52 trials including 9917 patients indicated that permethrin (the reference treatment) had a significantly higher cure rate than sulfur, malathion, lindane, crotamiton, and benzyl benzoate. Combination permethrin plus oral ivermectin had a nonsignificantly higher cure rate than permethrin. Combination permethrin plus oral ivermectin was ranked highest in terms of cure, topical ivermectin in terms of persistent itching, and synergized pyrethrins in terms of adverse events. On the basis of clustered ranking, permethrin, oral ivermectin, and synergized pyrethrins seemed to retain balance between cure and adverse events.
LIMITATIONS
There are small numbers of trials and patients in some comparisons and a high risk of bias in some trials.
CONCLUSION
There is no 1 treatment that ranked highest in all aspects. Physicians should consider the drug's efficacy and safety profiles, along with ease of administration.
Topics: Benzoates; Drug Therapy, Combination; Hexachlorocyclohexane; Humans; Insecticides; Ivermectin; Malathion; Network Meta-Analysis; Permethrin; Randomized Controlled Trials as Topic; Scabies; Sulfur; Toluidines
PubMed: 30654070
DOI: 10.1016/j.jaad.2019.01.004 -
Archives of Public Health = Archives... 2018Acute poisoning is a common reason for emergency department visit and hospitalization worldwide with major morbidity and mortality. The burden of poisoning exposures in... (Review)
Review
BACKGROUND
Acute poisoning is a common reason for emergency department visit and hospitalization worldwide with major morbidity and mortality. The burden of poisoning exposures in Africa is a significant public health concern, but only 10 of 58 countries have poisons information centers (PICs).
OBJECTIVE
The primary intention of our current review is to explore and summarize the published evidence on the patterns and epidemiology of poisoning in Ethiopia.
METHOD
PubMed and Scopus were searched for primary, case series and human studies for publications from inception to July 2017. A manual search for additional relevant studies using references from retrieved articles was also performed. Only studies that reported acute poisoning in both pediatric and adult patients were included. From the screened articles, data were extracted for baseline characteristics and relevant end points such as case fatality rate, time for health institution presentation and length of hospital stay.
RESULT
Initial entry and search resulted in the retrieval of 332 articles. Finally, 9 studies comprised of 4763 participants were included in this current review. In 78% of the studies included in this review, acute poisoning is reported to be more prevalent in females. Acute poisoning was revealed to be prevalent in less than 30 years old. Organophosphates and household cleaning agents were the predominant agents of acute poisoning. Intentional poisoning was identified responsible for the majority of acute poisoning cases and factors such as psychiatric problems, and quarrel were identified as the underlying reasons for poisoning. Time of presentation to health institution after poisoning, length of hospital stay and case fatality rate were reported and lies in the ranges between 0.2 h-24 h, 0.5 days-17.7 days and 0-14.8%, respectively.
CONCLUSION
The occurrence of acute poisoning was higher in females and common in less than 30 years of age, making this a real public health burden in Ethiopia. Psychiatric problems, quarrel and substance abuse were identified as the most common reasons for acute poisoning. Awareness creation how to handle chemicals and prescribed drugs and psychiatric consultations should be in place for the community.
PubMed: 29988616
DOI: 10.1186/s13690-018-0275-3 -
Journal of Medical Toxicology :... Mar 2018Organophosphates (OP) account for the majority of pesticide-related unintentional or intentional poisonings in lower- and middle-income countries. The therapeutic role... (Meta-Analysis)
Meta-Analysis
Organophosphates (OP) account for the majority of pesticide-related unintentional or intentional poisonings in lower- and middle-income countries. The therapeutic role of atropine is well-established for patients with acute OP poisoning. The benefit of adding 2-pyridine aldoxime methyl chloride (2-PAM), however, is controversial. We performed a systematic review and meta-analysis of available randomized controlled trials (RCT) to compare 2-PAM plus atropine in comparison to atropine alone for acute OP poisoning. We searched PubMed, EMBASE, and SCOPUS up to March 2017. The Cochrane review handbook was used to assess the risk of bias. Data were abstracted and risk ratios (RR) were calculated for mortality, rate of intubation, duration of intubation, intermediate syndrome, and complications such as hospital-acquired infections, dysrhythmias, and pulmonary edema. We found five studies comprising 586 patients with varying risks of bias. The risk of death (RR = 1.5, 95% CI 0.9-2.5); intubation (RR = 1.3, 95% CI 1.0-1.6); intermediate syndrome (RR = 1.6, 95% CI 1.0-2.6); complications (RR = 1.2, 95% CI 0.8-1.8); and the duration of intubation (mean difference 0.0, 95% CI - 1.6-1.6) were not significantly different between the atropine plus 2-PAM and atropine alone. Based on our meta-analysis of the available RCTs, 2-PAM was not shown to improve outcomes in patients with acute OP poisoning.
Topics: Animals; Antidotes; Cholinesterase Reactivators; Humans; Organophosphate Poisoning; Pralidoxime Compounds
PubMed: 29230717
DOI: 10.1007/s13181-017-0636-2 -
Journal of Applied Toxicology : JAT Jan 2018Incidents involving the release of chemical agents can pose significant risks to public health. In such an event, emergency decontamination of affected casualties may... (Review)
Review
Incidents involving the release of chemical agents can pose significant risks to public health. In such an event, emergency decontamination of affected casualties may need to be undertaken to reduce injury and possible loss of life. To ensure these methods are effective, human volunteer trials (HVTs) of decontamination protocols, using simulant contaminants, have been conducted. Simulants must be used to mimic the physicochemical properties of more harmful chemicals, while remaining non-toxic at the dose applied. This review focuses on studies that employed chemical warfare agent simulants in decontamination contexts, to identify those simulants most suitable for use in HVTs of emergency decontamination. Twenty-two simulants were identified, of which 17 were determined unsuitable for use in HVTs. The remaining simulants (n = 5) were further scrutinized for potential suitability according to toxicity, physicochemical properties and similarities to their equivalent toxic counterparts. Three suitable simulants, for use in HVTs were identified; methyl salicylate (simulant for sulphur mustard), diethyl malonate (simulant for soman) and malathion (simulant for VX or toxic industrial chemicals). All have been safely used in previous HVTs, and have a range of physicochemical properties that would allow useful inference to more toxic chemicals when employed in future studies of emergency decontamination systems.
Topics: Chemical Warfare Agents; Databases, Factual; Decontamination; Healthy Volunteers; Humans; In Vitro Techniques; Lethal Dose 50; Malathion; Malonates; Salicylates
PubMed: 28990191
DOI: 10.1002/jat.3527 -
The Cochrane Database of Systematic... Jul 2017Salivary gland dysfunction is an 'umbrella' term for the presence of either xerostomia (subjective sensation of dryness), or salivary gland hypofunction (reduction in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Salivary gland dysfunction is an 'umbrella' term for the presence of either xerostomia (subjective sensation of dryness), or salivary gland hypofunction (reduction in saliva production). It is a predictable side effect of radiotherapy to the head and neck region, and is associated with a significant impairment of quality of life. A wide range of pharmacological interventions, with varying mechanisms of action, have been used for the prevention of radiation-induced salivary gland dysfunction.
OBJECTIVES
To assess the effects of pharmacological interventions for the prevention of radiation-induced salivary gland dysfunction.
SEARCH METHODS
Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 14 September 2016); the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 8) in the Cochrane Library (searched 14 September 2016); MEDLINE Ovid (1946 to 14 September 2016); Embase Ovid (1980 to 14 September 2016); CINAHL EBSCO (Cumulative Index to Nursing and Allied Health Literature; 1937 to 14 September 2016); LILACS BIREME Virtual Health Library (Latin American and Caribbean Health Science Information database; 1982 to 14 September 2016); Zetoc Conference Proceedings (1993 to 14 September 2016); and OpenGrey (1997 to 14 September 2016). We searched the US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases.
SELECTION CRITERIA
We included randomised controlled trials, irrespective of their language of publication or publication status. Trials included participants of all ages, ethnic origin and gender, scheduled to receive radiotherapy on its own or in addition to chemotherapy to the head and neck region. Participants could be outpatients or inpatients. We included trials comparing any pharmacological agent regimen, prescribed prophylactically for salivary gland dysfunction prior to or during radiotherapy, with placebo, no intervention or an alternative pharmacological intervention. Comparisons of radiation techniques were excluded.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included 39 studies that randomised 3520 participants; the number of participants analysed varied by outcome and time point. The studies were ordered into 14 separate comparisons with meta-analysis only being possible in three of those.We found low-quality evidence to show that amifostine, when compared to a placebo or no treatment control, might reduce the risk of moderate to severe xerostomia (grade 2 or higher on a 0 to 4 scale) at the end of radiotherapy (risk ratio (RR) 0.35, 95% confidence interval (CI) 0.19 to 0.67; P = 0.001, 3 studies, 119 participants), and up to three months after radiotherapy (RR 0.66, 95% CI 0.48 to 0.92; P = 0.01, 5 studies, 687 participants), but there is insufficient evidence that the effect is sustained up to 12 months after radiotherapy (RR 0.70, 95% CI 0.40 to 1.23; P = 0.21, 7 studies, 682 participants). We found very low-quality evidence that amifostine increased unstimulated salivary flow rate up to 12 months after radiotherapy, both in terms of mg of saliva per 5 minutes (mean difference (MD) 0.32, 95% CI 0.09 to 0.55; P = 0.006, 1 study, 27 participants), and incidence of producing greater than 0.1 g of saliva over 5 minutes (RR 1.45, 95% CI 1.13 to 1.86; P = 0.004, 1 study, 175 participants). However, there was insufficient evidence to show a difference when looking at stimulated salivary flow rates. There was insufficient (very low-quality) evidence to show that amifostine compromised the effects of cancer treatment when looking at survival measures. There was some very low-quality evidence of a small benefit for amifostine in terms of quality of life (10-point scale) at 12 months after radiotherapy (MD 0.70, 95% CI 0.20 to 1.20; P = 0.006, 1 study, 180 participants), but insufficient evidence at the end of and up to three months postradiotherapy. A further study showed no evidence of a difference at 6, 12, 18 and 24 months postradiotherapy. There was low-quality evidence that amifostine is associated with increases in: vomiting (RR 4.90, 95% CI 2.87 to 8.38; P < 0.00001, 5 studies, 601 participants); hypotension (RR 9.20, 95% CI 2.84 to 29.83; P = 0.0002, 3 studies, 376 participants); nausea (RR 2.60, 95% CI 1.81 to 3.74; P < 0.00001, 4 studies, 556 participants); and allergic response (RR 7.51, 95% CI 1.40 to 40.39; P = 0.02, 3 studies, 524 participants).We found insufficient evidence (that was of very low quality) to determine whether or not pilocarpine performed better or worse than a placebo or no treatment control for the outcomes: xerostomia, salivary flow rate, survival, and quality of life. There was some low-quality evidence that pilocarpine was associated with an increase in sweating (RR 2.98, 95% CI 1.43 to 6.22; P = 0.004, 5 studies, 389 participants).We found insufficient evidence to determine whether or not palifermin performed better or worse than placebo for: xerostomia (low quality); survival (moderate quality); and any adverse effects.There was also insufficient evidence to determine the effects of the following interventions: biperiden plus pilocarpine, Chinese medicines, bethanechol, artificial saliva, selenium, antiseptic mouthrinse, antimicrobial lozenge, polaprezinc, azulene rinse, and Venalot Depot (coumarin plus troxerutin).
AUTHORS' CONCLUSIONS
There is some low-quality evidence to suggest that amifostine prevents the feeling of dry mouth in people receiving radiotherapy to the head and neck (with or without chemotherapy) in the short- (end of radiotherapy) to medium-term (three months postradiotherapy). However, it is less clear whether or not this effect is sustained to 12 months postradiotherapy. The benefits of amifostine should be weighed against its high cost and side effects. There was insufficient evidence to show that any other intervention is beneficial.
Topics: Amifostine; Drugs, Chinese Herbal; Female; Fibroblast Growth Factor 7; Humans; Male; Pilocarpine; Quality of Life; Radiation-Protective Agents; Radiotherapy; Randomized Controlled Trials as Topic; Saliva, Artificial; Salivary Gland Diseases; Salivary Glands; Salivation; Xerostomia
PubMed: 28759701
DOI: 10.1002/14651858.CD012744