Influence of manure application method on veterinary medicine losses to water.

Veterinary medicines are routinely used within modern animal husbandry, which results in frequent detections within animal manures and slurries. The application of manures to land as a form of organic fertiliser presents a pathway by which these bioactive chemicals can enter the environment. However, to date, there is limited understanding regarding the influence of commonly used manure application methods on veterinary medicine fate in soil systems. To bridge this knowledge gap, a semi-field study was conducted to assess the influence of commonly used application methods such as, broadcast, chisel sweep, and incorporation on veterinary medicine losses to waters. A range of veterinary medicines were selected and applied as a mixture; these were enrofloxacin, florfenicol, lincomycin, meloxicam, oxytetracycline, sulfadiazine, trimethoprim and tylosin. All the assessed veterinary medicines were detected within surface runoff and leachates, and the concentrations generally decreased throughout the irrigation period. The surface runoff concentrations ranged from 0.49 to 183.47 µg/L and 2.26-236.83 µg/L for the bare soil and grass assessments respectively. The leachate concentrations ranged from 0.04 to 309.66 µg/L and 0.33-37.79 µg/L for the bare soil and grass assessments respectively. More advanced application methods (chisel sweep) were found to significantly reduce the mass loads of veterinary medicines transported to surface runoff and leachate by 13-56% and 49-88% over that of broadcast. Incorporating pig slurries reduced the losses further with surface runoff and leachate losses being 13-56% and 49-88% lower than broadcast. Our results show that manure application techniques have a significant effect on veterinary medicine fate in the environment and as such these effects should be considered in the decision-making processes for the management of manures as well as from a risk mitigation perspective for aquatic compartments.

The effect of anaerobic pig slurry redox potentials on the degradation of veterinary medicines.

Veterinary medicines are frequently used within intensive livestock husbandry and there has been a growing interest regarding their fate in the environment. However, research has seldom assessed the influence of pig slurry properties on the fate of veterinary medicines even though such an understanding is essential for a more robust environmental risk assessment. Changes within manure degradation rates have the potential to alter the concentration of antibiotics applied to land, and the outcome of the risk assessment. The aim of this work was to investigate whether commonly reported redox potentials affect the degradation rates of acetyl-salicylic acid, ceftiofur, florfenicol, oxytetracycline, sulfamethoxazole, and tylosin. The employed redox potentials were -100 mV (reduced), -250 mV (anaerobic) and -400 mV (very anaerobic). A compound specific relationship was observed where the degradation of ceftiofur, florfenicol, oxytetracycline and sulfamethoxazole was inhibited under reduced conditions over that of very anaerobic; the respective DT50 values were 0.7-1.84 h, 1.35-3.61 h, 22.2-49.8 h, 131-211 h and 35.4-94 h. In contrast, tylosin was found to degrade faster at reduced conditions over very anaerobic (DT50 6.88-19.4 h). The presented research demonstrates the importance of redox potential on degradation rates and suggests we need stringent and harmonized redox control to improve the environmental risk assessment of veterinary medicines. Environmental relevance and significance: Given the significant effect of anaerobic redox potentials on veterinary medicine fate tighter regulation is required in manure degradation trials.

High Concentrations of Pharmaceuticals in a Nigerian River Catchment.

Pharmaceutical contamination of the environment is recognized as a global problem although most research has focused on Europe and North America to date, and there remains a dearth of information for developing countries, including those in Africa. To address this data gap, the occurrence of 37 pharmaceuticals belonging to 19 therapeutic classes was monitored in surface water and effluents in Lagos State, Southwest Nigeria. Samples were collected quarterly between April 2017 and March 2018 from 22 sites, and 26 compounds were detected at least once, many in the µg/L range. Maximum concentrations for those compounds detected ranged from 75 to 129 µg L-1 , and even mean concentrations for 13 compounds were in the order of µg L-1 . These values are among the highest ever measured globally. Sewage effluent was more important than drug manufacturing waste in polluting rivers, although there are likely to be numerous unregulated sources of effluent being discharged to rivers that require further study, including urban waste collection areas and vacuum trucks that collect effluent. Seasonal trends in the data were complex, with some compounds being found at higher concentrations in the dry season and, conversely, others being greater during the wet period; this variation potentially relates to the variety of pollution sources in the catchment. Pharmaceuticals are indispensable to human health, although their usage and discharge into the aquatic environment may lead to ecological problems and antibiotic resistance. The data we present indicate that pharmaceutical pollution of freshwaters is a serious issue in Nigeria, and management efforts are needed to improve this problem. Environ Toxicol Chem 2022;41:551-558. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Assessing the influence of pig slurry pH on the degradation of selected antibiotic compounds.

Veterinary medicines are routinely used in animal husbandry and the environment may consequently be exposed to them via manure applications. This presents potential environmental and societal risks such as toxicological effects to aquatic/terrestrial organisms and the spread of antimicrobial resistance. Regulatory studies that assess the degradability of veterinary antibiotics during manure storage currently permit the use of just one manure per animal type although we speculate that heterogenic properties such as pH could be driving significant variability within degradation rates. To bridge this knowledge gap and assess degradation variability with pH, laboratory degradation studies were performed on a broad range of antibiotics (ceftiofur, florfenicol, oxytetracycline, sulfamethoxazole and tylosin) at three different environmentally relevant pH levels (5.5, 7, and 8.5). The effect of pig slurry pH on degradation rates was found to be significant and compound specific. Usually, acidic slurries were found to inhibit degradation when compared to neutral pH, for florfenicol, tylosin, and ceftiofur; the associated changes in DT50 (half-life) values were 2-209 h, 35.28-234 h, and 0.98-2.13 h, respectively. In some circumstances alkaline slurries were observed to enhance the degradation rate when compared to those for neutral pH, for tylosin, the respective changes in DT50 values were from 3.52 to 35.28 h. Comparatively, the degradation of sulfamethoxazole was enhanced by acidic conditions compared to neutral (DT50 20.6-31.6 h). Tentative identification of unknown transformation products (TPs) was achieved for sulfamethoxazole and florfenicol for the first time in pig slurries. These results reveal the importance of considering slurry pH when assessing the degradation of antibiotic compounds, which has implications for the acidification of manures and the environmental risk assessment for veterinary medicines. Environmental relevance and significance: Given the significant effect of pig slurry pH on degradation rates, manure degradation studies need to be harmonised and standardized, taking into account the influence of pH.

Analytical method development and validation for the quantification of metaldehyde in soil.

Previously published methods for the analysis of metaldehyde were adapted for its reliable quantification in soil extracts. Varied methanol-water extraction solvents were trialed, but the use of pure methanol proved to be the most reliable approach for the scaled down methodology. Analysis of metaldehyde was done using LC-MS. Initially the method had problems with matrix suppression of the signal. The method was therefore further developed to overcome this challenge to avoid the costs and time demands of laborious clean-up protocols. This modification to the method involved use of the BEH Phenyl column instead of the C18 column initially used, and optimization of the gradient flow of the mobile phase. The optimized LC-MS method was validated and used for further research applications. In brief,•We investigated the recovery of metaldehyde from spiked soil samples.•The optimized LC-MS method achieved acceptable metaldehyde recoveries (100-132%, 109% on average) for a range of soil types.•The optimized method was suitable for high through-put analyzes.

Highly variable soil dissipation of metaldehyde can explain its environmental persistence and mobility.

There are increasing concerns about the hazard posed to drinking water resources by persistent, mobile, and toxic (PMT) substances in the environment. For example, the extensive use of metaldehyde-based molluscicide to control slug populations in agricultural fields has frequently led to pollution of surface waters and contamination of drinking water at levels exceeding the statutory limit. Regulatory environmental fate assessments and studies in the literature did not predict that metaldehyde would be persistent in the environment, contrary to observations from monitoring schemes. To understand the reasons for this disparity, this study conducted a suite of degradation experiments, covering different soil types and environmentally realistic conditions in Northern Europe, and generated a distribution of DT50 values for metaldehyde to examine whether degradation rates are underestimated by current risk assessments. The results were found to vary, showing DT50 values ranging from 3.0 to 4150 days, which indicated that metaldehyde had the potential to become persistent. Lack of prior metaldehyde exposure, high moisture content, low temperature, and locally high metaldehyde concentration under pellets were identified as high-risk conditions for low pesticide biodegradation in UK soils.

Isolation and characterization of metaldehyde-degrading bacteria from domestic soils.

Metaldehyde is a common molluscicide, used to control slugs in agriculture and horticulture. It is resistant to breakdown by current water treatment processes, and its accumulation in drinking water sources leads to regular regulatory failures in drinking water quality. To address this problem, we isolated metaldehyde-degrading microbes from domestic soils. Two distinct bacterial isolates were cultured, that were able to grow prototrophically using metaldehyde as sole carbon and energy source. One isolate belonged to the genus Acinetobacter (strain designation E1) and the other isolate belonged to the genus Variovorax (strain designation E3). Acinetobacter E1 was able to degrade metaldehyde to a residual concentration < 1 nM, whereas closely related Acinetobacter strains were completely unable to degrade metaldehyde. Variovorax E3 grew and degraded metaldehyde more slowly than Acinetobacter E1, and residual metaldehyde remained at the end of growth of the Variovorax E3 strain. Biological degradation of metaldehyde using these bacterial strains or approaches that allow in situ amplification of metaldehyde-degrading bacteria may represent a way forward for dealing with metaldehyde contamination in soils and water.

Three methods for integration of environmental risk into the benefit-risk assessment of veterinary medicinal products.

Veterinary medicinal products (VMPs) require, as part of the European Union (EU) authorization process, consideration of both risks and benefits. Uses of VMPs have multiple risks (e.g., risks to the animal being treated, to the person administering the VMP) including risks to the environment. Environmental risks are not directly comparable to therapeutic benefits; there is no standardized approach to compare both environmental risks and therapeutic benefits. We have developed three methods for communicating and comparing therapeutic benefits and environmental risks for the benefit-risk assessment that supports the EU authorization process. Two of these methods support independent product evaluation (i.e., a summative classification and a visual scoring matrix classification); the other supports a comparative evaluation between alternative products (i.e., a comparative classification). The methods and the challenges to implementing a benefit-risk assessment including environmental risk are presented herein; how these concepts would work in current policy is discussed. Adaptability to scientific and policy development is considered. This work is an initial step in the development of a standardized methodology for integrated decision-making for VMPs.

Toxicological and ecotoxicological risk-based prioritization of pharmaceuticals in the natural environment.

Approximately 1500 active pharmaceutical ingredients are currently in use; however, the environmental occurrence and impacts of only a small proportion of these have been investigated. Recognizing that it would be impractical to monitor and assess all pharmaceuticals that are in use, several previous studies have proposed the use of prioritization approaches to identify substances of most concern so that resources can be focused on these. All of these previous approaches suffer from limitations. In the present study, the authors draw on experience from previous prioritization exercises and present a holistic approach for prioritizing pharmaceuticals in the environment in terms of risks to aquatic and soil organisms, avian and mammalian wildlife, and humans. The approach considers both apical ecotoxicological endpoints as well as potential nonapical effects related to the therapeutic mode of action. Application of the approach is illustrated for 146 active pharmaceuticals that are used either in the community or in hospital settings in the United Kingdom. Using the approach, 16 compounds were identified as a potential priority. These substances include compounds belonging to the antibiotic, antidepressant, anti-inflammatory, antidiabetic, antiobesity, and estrogen classes as well as associated metabolites. In the future, the prioritization approach should be applied more broadly around the different regions of the world. Environ Toxicol Chem 2016;35:1550-1559. © 2016 SETAC.

Combination therapy with antibiotics and anthrax immune globulin intravenous (AIGIV) is potentially more effective than antibiotics alone in rabbit model of inhalational anthrax.

BACKGROUND: We have evaluated the therapeutic efficacy of AIGIV when given in combination with levofloxacin and the effective window of treatment to assess the added benefit provided by AIGIV over standard antibiotic treatment alone in a New Zealand white rabbit model of inhalational anthrax. METHODS: Rabbits were exposed to lethal dose of aerosolized spores of Bacillus anthracis (Ames strain) and treated intravenously with either placebo, (normal immune globulin intravenous, IGIV) or 15 U/kg of AIGIV, along with oral levofloxacin treatment at various time points (30-96 hours) after anthrax exposure. RESULTS: The majority of treated animals (>88%) survived in both treatment groups when treatment was initiated within 60 hours of post-exposure. However, reduced survival of 55%, 33% and 25% was observed for placebo + levofloxacin group when the treatment was initiated at 72, 84 and 96 hours post-exposure, respectively. Conversely, a survival rate of 65%, 40% and 71% was observed in the AIGIV + levofloxacin treated groups at these time points. CONCLUSIONS: The combination of AIGIV with antibiotics provided an improvement in survival compared to levofloxacin treatment alone when treatment was delayed up to 96 hours post-anthrax exposure. Additionally, AIGIV treatment when given as an adjunct therapy at any of the time points tested did not interfere with the efficacy of levofloxacin.

Nanopesticides: guiding principles for regulatory evaluation of environmental risks.

Nanopesticides or nano plant protection products represent an emerging technological development that, in relation to pesticide use, could offer a range of benefits including increased efficacy, durability, and a reduction in the amounts of active ingredients that need to be used. A number of formulation types have been suggested including emulsions (e.g., nanoemulsions), nanocapsules (e.g., with polymers), and products containing pristine engineered nanoparticles, such as metals, metal oxides, and nanoclays. The increasing interest in the use of nanopesticides raises questions as to how to assess the environmental risk of these materials for regulatory purposes. Here, the current approaches for environmental risk assessment of pesticides are reviewed and the question of whether these approaches are fit for purpose for use on nanopesticides is addressed. Potential adaptations to existing environmental risk assessment tests and procedures for use with nanopesticides are discussed, addressing aspects such as analysis and characterization, environmental fate and exposure assessment, uptake by biota, ecotoxicity, and risk assessment of nanopesticides in aquatic and terrestrial ecosystems. Throughout, the main focus is on assessing whether the presence of the nanoformulation introduces potential differences relative to the conventional active ingredients. The proposed changes in the test methodology, research priorities, and recommendations would facilitate the development of regulatory approaches and a regulatory framework for nanopesticides.

Investigation into the occurrence in food of veterinary medicines, pharmaceuticals, and chemicals used in personal care products.

Human exposure to emerging contaminants by indirect routes is of increasing interest. This study assessed the contamination of food by chemicals used in human pharmaceuticals (HPs), veterinary medicines (VMs), and personal care products (PCPs). A prioritization study was undertaken to identify the chemicals and food-producing scenarios most likely to result in contamination of food. Around 400 samples of mushrooms, vegetables, aquaculture products, and animal tissues were collected from sites in the United Kingdom, along with aquaculture products imported from Southeast Asia. A number of multianalyte methods were developed and validated for the analysis of the prioritized compounds in these samples. The analysis of all sample-method combinations required approximately 18000 determinations. Around 325 individual residues, including parabens, musk compounds, and antibiotics, were detected in 118 individual samples, but mostly at low nanograms per gram concentrations. Results suggest that the limited contamination of target chemicals occurred in the realistic food-producing scenarios investigated.

Occurrence, degradation, and effect of polymer-based materials in the environment.

There is now a plethora of polymer-based materials (PBMs) on the market, because of the increasing demand for cheaper consumable goods, and light-weight industrial materials. Each PBM constitutes a mixture of their representative polymer/sand their various chemical additives. The major polymer types are polyethylene, polypropylene,and polyvinyl chloride, with natural rubber and biodegradable polymers becoming increasingly more important. The most important additives are those that are biologically active, because to be effective such chemicals often have properties that make them resistant to photo-degradation and biodegradation. During their lifecycle,PBMs can be released into the environment form a variety of sources. The principal introduction routes being general littering, dumping of unwanted waste materials,migration from landfills and emission during refuse collection. Once in the environment,PBMs are primarily broken down by photo-degradation processes, but due to the complex chemical makeup of PBMs, receiving environments are potentially exposed to a mixture of macro-, meso-, and micro-size polymer fragments, leached additives, and subsequent degradation products. In environments where sunlight is absent (i.e., soils and the deep sea) degradation for most PBMs is minimal .The majority of literature to date that has addressed the environmental contamination or disposition of PBMs has focused on the marine environment. This is because the oceans are identified as the major sink for macro PBMs, where they are known to present a hazard to wildlife via entanglement and ingestion. The published literature has established the occurrence of microplastics in marine environment and beach sediments, but is inadequate as regards contamination of soils and freshwater sediments. The uptake of microplastics for a limited range of aquatic organisms has also been established, but there is a lack of information regarding soil organisms, and the long-term effects of microplastic uptake are also less well understood.There is currently a need to establish appropriate degradation test strategies consistent with realistic environmental conditions, because the complexity of environmental systems is lost when only one process (e.g., hydrolysis) is assessed in isolation. Enhanced methodologies are also needed to evaluate the impact of PBMs to soil and freshwater environments.

Do natural rubber latex condoms pose a risk to aquatic systems?

The presence and potential adverse effects of plastic-polymers in the environment are receiving increasing attention in the popular and scientific press. However, quantifying emissions, exposure and effects of these materials remains a challenge. This paper describes the application of a questionnaire survey to quantify emissions of condom material from the domestic household to the sewage waste stream. Condoms are an important mainstay for birth control and the reduction of sexually transmitted infections. Survey participants were estimated to flush condoms down the toilet 2.96% of the time, and emissions were calculated as 0.99 mg of condom material per person per day. Using information on screening efficiencies at sewage treatment plants, the questionnaire data was combined with a GIS-based water quality model (LF2000-WQX) to predicted environmental concentrations (PEC) in a UK river basin catchment. Annual average PECs of condom material were 0.08-0.2 µg L(-1), under the model scenario used. To put these PECs into context, rubber latex condom material was degraded in outdoor microcosms. This resulted in the formation of a complex mixture of substances including chemical degradation products and particles in the nano range. The direct effects of the degradation mixture were investigated using two freshwater organisms with different life cycle traits, the water column crustacean Daphnia magna and the sediment-dwelling larval of Chironomus riparius. Ecotoxicity tests investigated both acute and chronic endpoints and were shown to exhibit no toxic effects. This precluded the derivation of a genuine no-effect concentration. Hence, the results suggest that limited risk to invertebrates is associated with latex condom degradation products to the organisms tested. Future studies should extend this risk framework to assess risks of condoms to other taxonomic groups as well as the risks of other polymer materials.

Environmental fate of processed natural rubber latex.

In this study, processed natural rubber latex was degraded in outdoor aquatic microcosms, under a number of treatment scenarios for 200 days. The analytical strategy adopted aimed to characterise a range of volatile, semi-volatile and non-volatile substances. Zinc, was shown to migrate from the latex into solution and increase in concentration over time. Dissolved compounds for which predicted formulas were generated largely consisted of oxygen containing compounds, and are potential oxidised polyisoprene oligomers of various chain lengths. A classification of samples based on principal component analysis showed a clear separation of the degraded latex samples from the representative controls. This technique identified an increase in the complexity of the substances produced and showed that these substances undergo further degradation and transformation processes. A number of volatile substances were also identified indicating the atmosphere to be a potential receiving environmental compartment for polymer degradates. Overall, the results show that complex mixtures of substances are produced when polymer-based materials degrade under environmental conditions.

Effects of environmental conditions on latex degradation in aquatic systems.

Following use polymer materials may be released to the natural environment distributed to various environmental compartments and may undergo a variety of mechanical and chemical weathering processes. This study characterised the degradation of a latex polymer of different thicknesses under a range of environmental conditions in outdoor microcosms. Samples were immersed in either demineralised water, artificial freshwater and marine water media and exposed for a period of 200-250 days with exposure starting at different times of the year. Effects of pH, agitation and the exclusion of light on degradation were also studied. At the end of the exposure period, recovery of polymer material ≥ 1.6 µm ranged from a low of 22.04% (± 16.35, for the freshwater treatment at pH5.5) to a high of 97.73% (± 0.38, for the exclusion of light treatment). The disappearance of the bulk material corresponded to an increase in nanoparticles and dissolved organic material in the test media. Modelled degradation kinetics were characterised by multi-phasic degradation patterns and the results indicated degradation rate is affected by light intensity and polymer thickness. Mass balance analysis indicates that losses of volatile materials to the air compartment may also be occurring.

Investigation of the fate of trifluralin in shrimp.

Juvenile Pacific white shrimp (Litopenaeus vannamei) were exposed to trifluralin at 0.1 and 0.01 mg L(-1) for 72 h under controlled conditions. Samples of shrimp and tank water were collected at intervals up to 48 days after exposure. Analysis of the shrimp tissues by gas chromatography-mass spectrometry (GC-MS) and ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-qToF-MS) in combination with profiling and metabolite identification software (Agilent MET-ID and Mass Profiler Professional) detected the presence of parent trifluralin together with two main transformation products (TPs), 2-ethyl-7-nitro-5-(trifluoromethyl)benzimidazole (TP1) and 2-amino-6-nitro-4-(trifluoromethyl)phenyl)propylamine (TP2). The highest concentration of trifluralin, determined by GC-MS, was 120 µg kg(-1) at 0 day withdrawal. Residues of trifluralin (CCα = 0.25 µg kg(-1), CCß = 0.42 µg kg(-1)) were detectable for up to 7 days after exposure. Similarly, the highest concentrations of TP1 and TP 2, determined by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS), were 14 and 18 µg kg(-1), respectively. Residues of TP1 (CCα = 0.05 µg kg(-1), CCß = 0.09 µg kg(-1)) and TP2 (CCα = 0.1 µg kg(-1), CCß = 0.17 µg kg(-1)) were detectable for up to 4 and 24 withdrawal days, respectively.

Effects of repeated pulsed herbicide exposures on the growth of aquatic macrophytes.

Many contaminants are released into aquatic systems intermittently in a series of pulses. Pulse timing and magnitude can vary according to usage, compound-specific physicochemical properties, and use area characteristics. Standard laboratory ecotoxicity tests typically employ continuous exposure concentrations over defined durations and thus may not accurately and realistically reflect the effects of certain compounds on aquatic organisms, resulting in potential over- or underestimation. Consequently, the relative effects of pulsed (2 and 4 d) and continuous exposures of the duckweed Lemna minor to isoproturon, metsulfuron-methyl, and pentachlorophenol over a period of 42 d were explored in the present study. At the highest test concentrations, exposure of L. minor to pulses of metsulfuron-methyl resulted in effects on growth similar to those of an equivalent continuous exposure. For isoproturon, pulsed exposures had a lower impact than a corresponding continuous exposure, whereas the effect of pentachlorophenol delivered in pulses was greater. These differences may be explained by compound-specific uptake and degradation or dissipation rates in plants and the recovery potential that occurs following pulses for different pesticides. Given these results, use of a simple time-weighted average approach to estimate effects of intermittent exposures from short-term standard toxicity studies may not provide an accurate prediction that reflects realistic exposure scenarios. Development of mechanistic modeling approaches may facilitate better estimates of effects from intermittent exposures.

WITHDRAWN: Metoclopramide, thickened feedings, and positioning for gastro-oesophageal reflux in children under two years.

BACKGROUND: Gastro-esophageal reflux (GER) is the refluxing of gastric contents into the esophagus. Fifty per cent of all infants 0 to 3 months regurgitate at least once a day. This drops to 5% once infants are 10 to 12 months old. Three per cent of parents of 10 to 12 month old infants view this as a problem. OBJECTIVES: To investigate the effectiveness of thickened feeds, positioning, and metoclopramide as compared to placebo in improving the outcome of GER in developmentally normal infants aged one month to two years. SEARCH STRATEGY: Trials were identified by searching Cochrane Central Register of Controlled Trials (The Cochrane Library 2003), MEDLINE (January 1966 to 23 January 2003), EMBASE (January 1985 to 27 January 2003), and reference lists of articles. Searches in all databases were updated in April 2009. SELECTION CRITERIA: Randomised studies (parallel or cross over) which evaluated thickened feeds, positional alternations or metoclopramide for the treatment of GER in children between the age of one month and two years who were developmentally normal. DATA COLLECTION AND ANALYSIS: All three reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials. MAIN RESULTS: Twenty trials involving 771 children met the inclusion criteria: eight dealt with thickened feeds, five with positioning, and seven with metoclopramide. Few comparisons could be made, and so summary measures were often made with two or three studies. Thickened feeds reduce the regurgitation severity score (standardized mean difference (SMD) -0.94;95% confidence interval -1.35 to -0.52), as well as the frequency of emesis (SMD -0.91; confidence interval -1.22 to -0.61). The reflux index was not reduced (weighted mean difference (WMD) 0.48%; 95% confidence interval -3.27 to 4.23). All five positioning studies utilized esophageal pH monitoring as their outcome measure. Elevating the head of the crib for treating reflux in the supine position is not justifiable. The seven metoclopramide studies used a variety of outcomes. Compared to placebo, metoclopramide appears to reduce daily symptoms ( SMD -0.73; 95% confidence interval -1.16 to -0.30), and reduce the reflux index (WMD -2.80%; 95% confidence interval -5.58 to -0.01). It does increase side effects. AUTHORS' CONCLUSIONS: Thickened feeds are helpful in reducing the symptoms of GER. Elevating the head of the crib in the supine position does not have any effect. Metoclopramide may have some benefit in comparison to placebo in the symptomatic treatment for GER, but that must be weighed against possible side effects. .

Pathogen safety of intravenous Rh immunoglobulin liquid and other immune globulin products: enhanced nanofiltration and manufacturing process overview.

Plasma products for therapeutic use pose specific challenges in manufacturing to ensure products maintain biologic activity and are safe with respect to contamination and transmission of disease-causing agents. Various processes have demonstrated effectiveness in eliminating, reducing, or inactivating viral contaminants. Recently, the possibility of transmitting variant Creutzfeld-Jakob disease (vCJD) or transmissible spongiform encephalopathies (TSE) through blood-based products has become a concern. The present study involves the validation of a hyperimmune immunoglobulin manufacturing process incorporating a nanofiltration step with a nominal pore size of 20 nm for removal of viral contaminants and other adventitious agents. Processing intermediates during the manufacture of IV Rh IgG (WinRho SDF/WinRho SDF Liquid, Cangene Corporation, Manitoba, Canada) were spiked with model viruses and processed in scaled-down procedures to validate the viral reduction capacity of each step. Anion-exchange chromatography and solvent/detergent steps are known to contribute to virus removal and inactivation. The Planova 20 N nanofiltration step was effective in reducing model viruses representing a wide range of viral morphologies with varying degrees of resistance to physicochemical inactivation. All in-process and final batch testing met current standards for production of IV Rh IgG manufactured with the previously licensed filter, which had a larger nominal pore size of 35 nm. The manufacturing process, employing a Planova 35 N filtration step, has been proactively improved by the change to a smaller-pore 20 N filter. Replacement of the 35 N filter with the 20 N filter produces a similar product while enhancing the capability for removal of smaller viruses and prions.