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Clinical Toxicology (Philadelphia, Pa.) Jun 2020Organophosphorus (OP) insecticide self-poisoning is a global problem, killing tens of thousands of people every year. Oxidative stress has been proposed to play a...
Organophosphorus (OP) insecticide self-poisoning is a global problem, killing tens of thousands of people every year. Oxidative stress has been proposed to play a pathological role in OP poisoning, but whether it plays a direct toxic role is currently unclear. To determine whether there is consistent evidence of oxidative stress in patients with acute OP insecticide self-poisoning, and whether there are animal or human trial data that indicate that treatment of oxidative stress provides clinical benefit, which would suggest a direct toxic effect of oxidative stress. We conducted a systematic review using the PubMed, EMBASE and MEDLINE databases, and the Cochrane Database of Systematic reviews, based upon the following search terms and keywords: "organophosphate poisoning", "oxidative stress" and "antioxidant". All articles relevant to the aims of the study were included. Articles related to chronic OP poisoning, to use of medicines without antioxidant benefits, or to subjects other than oxidative stress were excluded. The search returned 256 results of which 17 studies were considered relevant and grouped under the following categories: observational human studies ( = 11) and intervention studies in animals ( = 4) and humans ( = 2). Oxidative damage to lipids and proteins was reported in all eleven human studies. Eight of nine studies reported variable increases in a weak marker of lipid peroxidation, malondialdehyde. In two case-control studies, erythrocyte membrane malondialdehyde concentrations were 380% and 160% higher in cases than controls, while plasma malondialdehyde concentrations were ∼63% higher in cases than controls in three case-control studies. In a prospective study, plasma malondialdehyde did not increase significantly from baseline in moderate or severely poisoned patients. Five case-control studies measured thiol residues as markers of protein oxidative damage and found variable changes after poisoning. No evidence of oxidative DNA damage was found in the one study that investigated it. After treatment with an antioxidant, all four studies showed an improvement in either markers of oxidative damage or antioxidant activity. One mouse study with a relatively low risk of bias showed that administration of acetylcysteine 200 mg/kg reduced malondialdehyde by 35% and increased survival by more than 60%. We found two small randomised controlled trials reporting the use of acetylcysteine as an adjunct to standard treatment in acute OP poisoning. The trials found that acetylcysteine reduced atropine requirements by 77% and 55%, but did not affect clinically relevant outcomes. Several studies showed evidence of OP insecticide-induced oxidative damage and antioxidant activity, suggesting that endogenous antioxidant defences are triggered in acute OP poisoning. However, the markers of lipid peroxidation used were weak, there was high inter-individual variability between studies in results and quality, and marked variation between the OP insecticides involved. Animal data provide some evidence that antioxidants alleviate adverse effects of acute poisoning, suggesting that oxidative stress may directly cause clinical harm. Acetylcysteine appeared beneficial in animal studies, but this could be mediated increased synthesis of the endogenous detoxifying agent, glutathione, rather than through a direct antioxidant effect. The two human clinical studies were too small to provide any clear evidence to support the use of acetylcysteine in OP poisoning. Further research into the mechanisms of oxidative stress in acute OP poisoning, combined with large unambiguous clinical trials of antioxidants, are required before they can be used routinely in treatment.
Topics: Acute Disease; Animals; Antioxidants; Humans; Insecticides; Organophosphate Poisoning; Organophosphorus Compounds; Oxidative Stress
PubMed: 31810386
DOI: 10.1080/15563650.2019.1693589 -
Clinical Case Reports Nov 2019Clozapine is considered the golden standard in the treatment of therapy-resistant schizophrenia; however, it associated with bothersome side effects such as sialorrhea....
Clozapine is considered the golden standard in the treatment of therapy-resistant schizophrenia; however, it associated with bothersome side effects such as sialorrhea. Current evidence suggests that the sublingual use of atropine seems to be safe and effective and could be considered as a first-line treatment of clozapine-induced sialorrhea.
PubMed: 31788260
DOI: 10.1002/ccr3.2431 -
The Journal of Trauma and Acute Care... Oct 2019Acute noninfectious diarrhea is a common phenomenon in intensive care unit patients. Multiple treatments are suggested but the most effective management is unknown. A...
Antimotility agents for the treatment of acute noninfectious diarrhea in critically ill patients: A practice management guideline from the Eastern Association for the Surgery of Trauma.
BACKGROUND
Acute noninfectious diarrhea is a common phenomenon in intensive care unit patients. Multiple treatments are suggested but the most effective management is unknown. A working group of the Eastern Association for the Surgery of Trauma, aimed to evaluate the effectiveness of loperamide, diphenoxylate/atropine, and elemental diet on acute noninfectious diarrhea in critically ill adults and to develop recommendations applicable to daily clinical practice.
METHODS
The literature search identified 11 randomized controlled trials (RCT) appropriate for inclusion. The Grading of Recommendations Assessment, Development, and Evaluation methodology was applied to evaluate the effect of loperamide, diphenoxylate/atropine, and elemental diet on the resolution of noninfectious diarrhea in critically ill adults based on selected outcomes: improvement in clinical diarrhea, fecal frequency, time to the diarrhea resolution, and hospital length of stay.
RESULTS
The level of evidence was assessed as very low. Analyses of 10 RCTs showed that loperamide facilitates resolution of diarrhea. Diphenoxylate/atropine was evaluated in three RCTs and was as effective as loperamide and more effective than placebo. No studies evaluating elemental diet as an intervention in patients with diarrhea were found.
CONCLUSION
Loperamide and diphenoxylate/atropine are conditionally recommended to be used in critically ill patients with acute noninfectious diarrhea.
LEVEL OF EVIDENCE
Systematic Review/Guidelines, level III.
Topics: Adult; Antidiarrheals; Critical Illness; Diarrhea; Diet Therapy; Diphenoxylate; Gastrointestinal Motility; Humans; Loperamide; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 31574060
DOI: 10.1097/TA.0000000000002449 -
The Cochrane Database of Systematic... Aug 2019Amblyopia is defined as impaired visual acuity in one or both eyes without demonstrable abnormality of the visual pathway, and is not immediately resolved by wearing...
BACKGROUND
Amblyopia is defined as impaired visual acuity in one or both eyes without demonstrable abnormality of the visual pathway, and is not immediately resolved by wearing glasses.
OBJECTIVES
In performing this systematic review, we aimed to synthesize the best available evidence regarding the effectiveness and safety of conventional occlusion therapy compared to atropine penalization in treating amblyopia.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2018, Issue 8); Ovid MEDLINE; Ovid Embase; LILACS BIREME; ClinicalTrials.gov; ISRCTN; and the WHO ICTRP on 7 September 2018.
SELECTION CRITERIA
We included randomized/quasi-randomized controlled trials comparing conventional occlusion to atropine penalization for amblyopia.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened abstracts and full-text articles, abstracted data, and assessed risk of bias.
MAIN RESULTS
We included seven trials (five randomized controlled trials and two quasi-randomized controlled trials) conducted in six countries (China, India, Iran, Ireland, Spain, and the United States) with a total of 1177 amblyopic eyes. Three of these seven trials were from the original 2009 version of the review. We assessed two trials as having a low risk of bias across all domains, and the remaining five trials as having unclear or high risk of bias for some domains.As different occlusion modalities, atropine penalization regimens, and populations were used across the included trials, we did not conduct any meta-analysis due to clinical and statistical heterogeneity. Evidence from six trials (two at low risk of bias) suggests that atropine penalization is as effective as conventional occlusion in improving visual acuity. Similar improvement in visual acuity was reported at all time points at which it was assessed, ranging from five weeks (improvement of 1 line) to 10 years (improvement of greater than 3 lines). At six months, although most participants (363/522) come from a trial rated as at low risk of bias with a precise estimate (mean difference (MD) 0.03, 95% confidence interval (CI) 0.00 to 0.06), two other trials rated as at high risk of bias produced inconsistent estimates and wide confidence intervals (MD -0.02, 95% CI -0.11 to 0.07 and MD -0.14, 95% CI -0.23 to -0.05; moderate-certainty evidence). At 24 months, additional improvement was found in both groups, but there continued to be no meaningful difference between those receiving occlusion and those receiving atropine therapies (moderate-certainty evidence).We did not find any difference in ocular alignment, stereo acuity, or sound eye visual acuity between occlusion and atropine penalization groups (moderate-certainty evidence). Both treatments were well tolerated. Atropine was associated with better adherence (moderate-certainty evidence) and quality of life (moderate-certainty evidence), but also a higher reported risk of adverse events in terms of mild reduction in the visual acuity of the sound eye not requiring treatment and light sensitivity (high-certainty evidence). Skin, lid, or conjunctival irritation were more common among participants receiving patching than those receiving atropine (high-certainty evidence). Atropine penalization costs less than conventional occlusion.
AUTHORS' CONCLUSIONS
Both conventional occlusion and atropine penalization produce visual acuity improvement in the amblyopic eye. Atropine penalization appears to be as effective as conventional occlusion, although the magnitude of improvement differed among the trials we analyzed.
Topics: Amblyopia; Atropine; Child; Child, Preschool; Humans; Occlusive Dressings; Ophthalmic Solutions; Randomized Controlled Trials as Topic; Visual Acuity
PubMed: 31461545
DOI: 10.1002/14651858.CD006460.pub3 -
International Journal of Ophthalmology 2019To evaluate the effects of atropine 0.01% on slowing myopia progression.
AIM
To evaluate the effects of atropine 0.01% on slowing myopia progression.
METHODS
We searched for relevant studies in the Cochrane Library, PubMed, Embase, Ovid, CBM, CNKI, VIP and Wan Fang Data in Chinese. A supplementary search was conducted in OpenGrey (System for Information on Grey Literature in Europe), the ISRCTN registry, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP) from the dates of inception to June 30, 2018.
RESULTS
Seven randomized controlled trials (RCTs) with a total of 1079 subjects were included (505 in the atropine 0.01% group and 574 in the control group). The results showed that the atropine 0.01% group exhibited significantly greater control of axial growth than the control group [MD=-0.12, 95%CI (-0.19, -0.06)]. There was also a statistically significant difference between the atropine 0.01% and control groups in the changes in axial length [MD=-0.14, 95%CI (-0.25, -0.03)], but the quality of evidence was low. There were no significant differences between the atropine 0.01% and control groups in the overall effect with respect to diopter value, change in diopter, distance vision and intraocular pressure [MD=0.08, 95%CI (-0.27, 0.42); MD=0.09, 95%CI (-0.17, 0.36); MD= -0.01, 95%CI (-0.02, 0.00); MD=0.08, 95%CI (-0.56,0.40)]. The sensitivity analysis showed that the conclusion of the Meta-analysis is relatively stable. With respect to adverse events, there were significant differences between the atropine 0.01% and control groups [OR=0.26, 95%CI (0.11, 0.61)].
CONCLUSION
Based on the available evidence, atropine 0.01% eye drops offer benefits in controlling axial growth and safety without causing significant differences in diopter values, distance vision and intraocular pressure.
PubMed: 31456926
DOI: 10.18240/ijo.2019.08.16 -
Environmental Science and Pollution... Oct 2019Glucagon-like peptide-1 (GLP-1) is involved in postprandial glucose homeostasis. Secretion of which involves a cholinergic pathway. Anticholinergic agent like atropine...
Glucagon-like peptide-1 (GLP-1) is involved in postprandial glucose homeostasis. Secretion of which involves a cholinergic pathway. Anticholinergic agent like atropine could act as a competitive antagonist of acetylcholine at muscarinic receptors. This review explores studies that assess the role of atropine in GLP-1 secretion. We selected published original articles from PubMed, Science Direct, The Cochrane Library, Trip, Google and the reference lists of the selected articles. Reporting was done according to the PRISMA statement. Relevant standard and previously published tools were used to assess the risk of bias of the selected articles. Twelve articles out of 185 search results fulfilled the review criteria. Eight were in vivo studies (six animal and two human studies), three were ex vivo studies and one was an in vitro study. Animal studies had rats, mice, pigs and monkeys as the subjects. Human studies involved healthy men and women. Majority of the studies reported an atropine-mediated attenuation of GLP-1 secretion and postprandial secretion of GLP-1 was mainly affected. However, atropine failed to significantly affect GLP-1 secretion when dipeptidyl peptidase-4 (DPP-4) enzyme was inhibited.
Topics: Adult; Animals; Atropine; Dipeptidyl Peptidase 4; Female; Glucagon-Like Peptide 1; Humans; Male; Mice; Postprandial Period; Rats; Swine
PubMed: 31446595
DOI: 10.1007/s11356-019-06227-2