Objective: Funnel plots (plots of effect estimates against sample size) may be useful to detect bias in meta-analyses that were later contradicted by large trials. We examined whether a simple test of asymmetry of funnel plots predicts discordance of results when meta-analyses are compared to large trials, and we assessed the prevalence of bias in published meta-analyses. Design: Medline search to identify pairs consisting of a meta-analysis and a single large trial (concordance of results was assumed if effects were in the same direction and the meta-analytic estimate was within 30% of the trial); analysis of funnel plots from 37 meta-analyses identified from a hand search of four leading general medicine journals 1993-6 and 38 meta-analyses from the second 1996 issue of the Cochrane Database of Systematic Reviews . Main outcome measure: Degree of funnel plot asymmetry as measured by the intercept from regression of standard normal deviates against precision. Results: In the eight pairs of meta-analysis and large trial that were identified (five from cardiovascular medicine, one from diabetic medicine, one from geriatric medicine, one from perinatal medicine) there were four concordant and four discordant pairs. In all cases discordance was due to meta-analyses showing larger effects. Funnel plot asymmetry was present in three out of four discordant pairs but in none of concordant pairs. In 14 (38%) journal meta-analyses and 5 (13%) Cochrane reviews, funnel plot asymmetry indicated that there was bias. Conclusions: A simple analysis of funnel plots provides a useful test for the likely presence of bias in meta-analyses, but as the capacity to detect bias will be limited when meta-analyses are based on a limited number of small trials the results from such analyses should be treated with considerable caution. Key messages Systematic reviews of randomised trials are the best strategy for appraising evidence; however, the findings of some meta-analyses were later contradicted by large trials Funnel plots, plots of the trials9 effect estimates against sample size, are skewed and asymmetrical in the presence of publication bias and other biases Funnel plot asymmetry, measured by regression analysis, predicts discordance of results when meta-analyses are compared with single large trials Funnel plot asymmetry was found in 38% of meta-analyses published in leading general medicine journals and in 13% of reviews from the Cochrane Database of Systematic Reviews Critical examination of systematic reviews for publication and related biases should be considered a routine procedure

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Bias in meta-analysis detected by a simple, graphical test

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(06)69665-7.pdf

Developmental neurotoxicity of industrial chemicals

Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children

Organic agriculture has a history of being contentious and is considered by some as an inefficient approach to food production. Yet organic foods and beverages are a rapidly growing market segment in the global food industry. Here, we examine the performance of organic farming in light of four key sustainability metrics: productivity, environmental impact, economic viability and social wellbeing. Organic farming systems produce lower yields compared with conventional agriculture. However, they are more profitable and environmentally friendly, and deliver equally or more nutritious foods that contain less (or no) pesticide residues, compared with conventional farming. Moreover, initial evidence indicates that organic agricultural systems deliver greater ecosystem services and social benefits. Although organic agriculture has an untapped role to play when it comes to the establishment of sustainable farming systems, no single approach will safely feed the planet. Rather, a blend of organic and other innovative farming systems is needed. Significant barriers exist to adopting these systems, however, and a diversity of policy instruments will be required to facilitate their development and implementation.

Organic agriculture in the twenty-first century.

Synthetic organophosphorus compounds are used as pesticides, plasticizers, air fuel ingredients and chemical warfare agents. Organophosphorus compounds are the most widely used insecticides, accounting for an estimated 34% of world-wide insecticide sales. Contamination of soil from pesticides as a result of their bulk handling at the farmyard or following application in the field or accidental release may lead occasionally to contamination of surface and ground water. Several reports suggest that a wide range of water and terrestrial ecosystems may be contaminated with organophosphorus compounds. These compounds possess high mammalian toxicity and it is therefore essential to remove them from the environments. In addition, about 200 000 metric tons of nerve (chemical warfare) agents have to be destroyed world-wide under Chemical Weapons Convention (1993). Bioremediation can offer an efficient and cheap option for decontamination of polluted ecosystems and destruction of nerve agents. The first micro-organism that could degrade organophosphorus compounds was isolated in 1973 and identified as Flavobacterium sp. Since then several bacterial and a few fungal species have been isolated which can degrade a wide range of organophosphorus compounds in liquid cultures and soil systems. The biochemistry of organophosphorus compound degradation by most of the bacteria seems to be identical, in which a structurally similar enzyme called organophosphate hydrolase or phosphotriesterase catalyzes the first step of the degradation. organophosphate hydrolase encoding gene opd (organophosphate degrading) gene has been isolated from geographically different regions and taxonomically different species. This gene has been sequenced, cloned in different organisms, and altered for better activity and stability. Recently, genes with similar function but different sequences have also been isolated and characterized. Engineered microorganisms have been tested for their ability to degrade different organophosphorus pollutants, including nerve agents. In this article, we review and propose pathways for degradation of some organophosphorus compounds by microorganisms. Isolation, characterization, utilization and manipulation of the major detoxifying enzymes and the molecular basis of degradation are discussed. The major achievements and technological advancements towards bioremediation of organophosphorus compounds, limitations of available technologies and future challenge are also discussed.

Microbial degradation of organophosphorus compounds

Acute neurotoxic effects during the cholinergic phase of organophosphorus insecticide poisoning and delayed neurotoxic effects appearing two to three weeks later are well recognized. We observed 10 patients who had paralysis of proximal limb muscles, neck flexors, motor cranial nerves, and respiratory muscles 24 to 96 hours after poisoning, after a well-defined cholinergic phase. The compounds involved were fenthion, monocrotophos, dimethoate, and methamidophos. Four patients urgently required ventilatory support. The paralytic symptoms lasted up to 18 days. A delayed polyneuropathy later developed in one patient. Three patients died. Electromyographic studies showed fade on tetanic stimulation, absence of fade on low-frequency stimulation, and absence of post-tetanic facilitation, suggestive of a postsynaptic defect. This neuromuscular junctional defect may have been the predominant cause of the paralytic symptoms, with neural and central components contributing to various degrees. Our patients appeared to have a distinct clinical entity (a so-called intermediate syndrome) that developed after the acute cholinergic crisis and before the expected onset of the delayed neuropathy.

Neurotoxic effects of organophosphorus insecticides. An intermediate syndrome.

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(02)11204-9.pdf

Pesticide poisoning in the developing world—a minimum pesticides list

Does pralidoxime affect outcome of management in acute organophosphorus poisoning

Organophosphorus insecticide poisoning

Polyneuropathy is a recognized complication of poisoning by some organophosphate plasticizers and insecticides.1 , 2 The hazards of organophosphate pesticides for human beings have been limited by screening of candidate compounds and exclusion of those that cause neuropathy in hens given median lethal doses. However, there have been a few reported patients with neuropathy due to various organophosphate pesticides — Mipafox,3 Leptophos,4 Trichlorphon (Chlorophos or Dipterex),5 and Trichloronate (Phytosol).6 We report here 10 isolated cases of acute polyneuropathy seen over three years in Sri Lanka. All 10 developed after poisoning by formulations of technical-grade Tamaron, whose main ingredient is methamidophos (0,S . . .

Nimal Senanayake

Papers

Neurotoxic effects of organophosphorus insecticides. An intermediate syndrome.

Pesticide poisoning in the developing world—a minimum pesticides list

Does pralidoxime affect outcome of management in acute organophosphorus poisoning

Organophosphorus insecticide poisoning

Acute Polyneuropathy after Poisoning by a New Organophosphate Insecticide