Topical NSAIDs for acute pain: a meta-analysis

BACKGROUND: A previous systematic review reported that topical NSAIDs were effective in relieving pain in acute conditions like sprains and strains, with differences between individual drugs for efficacy. More trials, a better understanding of trial quality and bias, and a reclassification of certain drugs necessitate a new review. METHODS: Studies were identified by searching electronic databases and writing to manufacturers. We selected randomised double blind trials comparing topical NSAID with either placebo or another active treatment in adults with acute pain, and extracted dichotomous information approximating to a 50% reduction in pain at one week, together with details of adverse events and withdrawals. Relative benefit and number-needed-to-treat (NNT), and relative risk and number-needed-to-harm (NNH) were calculated, with sensitivity analyses where appropriate to investigate differences between individual drugs and aspects of trial design. RESULTS: Twenty-six double blind placebo controlled trials had information from 2,853 patients for evaluation of efficacy. Topical NSAID was significantly better than placebo in 19 of the 26 trials, with a pooled relative benefit of 1.6 (95% confidence interval 1.4 to 1.7), and NNT of 3.8 (95% confidence interval 3.4 to 4.4) compared with placebo for the outcome of half pain relief at seven days. Results were not affected by outcome reported, or condition treated, but smaller trials yielded a larger estimate of efficacy. Indirect comparisons of individual topical NSAIDs showed that ketoprofen was significantly better than all other topical NSAIDs, while indomethacin was barely distinguished from placebo. Three trials, with 433 patients, compared topical with oral NSAID (two trials compared the same drug, one compared different drugs) and found no difference in efficacy. Local adverse events, systemic adverse events, or withdrawals due to an adverse event were rare, and no different between topical NSAID and placebo. CONCLUSIONS: Topical NSAIDs were effective and safe in treating acute painful conditions for one week

Regional analysis of groundwater nitrate concentrations and trends in Denmark in regard to agricultural influence

The act of balancing between an intensive agriculture with a high potential for nitrate pollution and a drinking water supply almost entirely based on groundwater is a challenge faced by Denmark and similar regions around the globe. Since the 1980s, regulations implemented by Danish farmers have succeeded in optimizing the N (nitrogen) management at farm level. As a result, the upward agricultural N surplus trend has been reversed, and the N surplus has reduced by 30–55% from 1980 to 2007 depending on region. The reduction in the N surplus served to reduce the losses of N from agriculture, with documented positive effects on nature and the environment in Denmark. In groundwater, the upward trend in nitrate concentrations was reversed around 1980, and a larger number of downward nitrate trends were seen in the youngest groundwater compared with the oldest groundwater. However, on average, approximately 48% of the oxic monitored groundwater has nitrate concentrations above the groundwater and drinking water standards of 50 mg l<sup>−1</sup>. Furthermore, trend analyses show that 33% of all the monitored groundwater has upward nitrate trends, while only 18% of the youngest groundwater has upward nitrate trends according to data sampled from 1988–2009. A regional analysis shows a correlation between a high level of N surplus in agriculture, high concentrations of nitrate in groundwater and the largest number of downward nitrate trends in groundwater in the livestock-dense northern and western parts of Denmark compared with the southeastern regions with lower livestock densities. These results indicate that the livestock farms dominating in northern and western parts of Denmark have achieved the largest reductions in N surpluses. Groundwater recharge age determinations allow comparison of long-term changes in N surplus in agriculture with changes in oxic groundwater quality. The presented data analysis is based on groundwater recharged from 1952–2003, but sampled from 1988–2009. Repetition of the nitrate trend analyses at five-year intervals using dating of the groundwater recharged in the coming years and a longer time series of the nitrate analyses can reveal the evolution in nitrate leaching from Danish agriculture during the past 10 yr. Similar analyses can be carried out to compare with other regions internationally

Ontwikkelingen in het monitoren van de effectiviteit van de Nitraatrichtlijn Actieprogramma's : Resultaten van de tweede MonNO3-workshop, 10-11 juni 2009

Lidstaten van de Europese Unie zijn verplicht om de waterkwaliteit en de effecten van hun mestbeleid daarop te monitoren en hierover te rapporteren aan de Europese Commissie. Uit een internationale workshop blijkt dat landen hun monitoringsverplichting verschillend invullen doordat voorschriften ontbreken. Een andere bevinding is dat de meeste landen de afgelopen zes jaren hebben geïnvesteerd in een uitbreiding van de monitoring van de waterkwaliteit. Deze uitbreiding kwam voort uit een discussie tussen de lidstaten en de Commissie over de wijze waarop het mestbeleid moet worden vormgegeven. Lidstaten proberen hun standpunten hierover te onderbouwen met aanvullende monitoring. Een andere reden voor een uitgebreidere monitoring is dat lidstaten die pas recentelijk bij de Unie zijn aangesloten, hun monitoringssysteem moeten aanpassen aan de richtlijnen. Het RIVM heeft de workshop in 2009 met het Deense Milieuonderzoeksinstituut (DMU), de Geologische Dienst voor Denemarken en Groenland (GEUS) en het LEI, onderdeel van Wageningen UR, georganiseerd. Aan deze tweede MonNO3- workshop namen twaalf landen uit Noordwest- en Midden-Europa deel. De workshop richtte zich vooral op de ontwikkelingen sinds 2003, het jaar dat de eerste MonNO3 workshop heeft plaatsgevonden. De tweede workshop heeft, net als de eerste, eraan bijgedragen dat landen kennis en informatie over het monitoren van effecten van het mestbeleid uitwisselen. De workshop stimuleerde bijvoorbeeld de discussie over voor- en nadelen van gebruikte benaderingen van de waterkwaliteitsmonitoring. Daarnaast was er aandacht voor het gebruik van de monitoringgegevens voor andere doeleinden dan de waterkwaliteitsmonitoring, bijvoorbeeld om maatregelen voor het mestbeleid te onderbouwen. Ten slotte stonden de deelnemers stil bij verbeteringen en uitbreidingen van meetnetten.Member States of the European Union are obliged both to monitor the quality of their waters and the effect of their Action Programmes on these waters and to report the results to the European Commission. These monitoring obligations have been interpreted differently by the various countries due to the lack of specific guidelines. Most countries, however, have increased their efforts to monitor water quality the last six years, primarily as a consequence of the discussion between the Member States and the European Commission on how the fertiliser policy should be designed and implemented. Member States try to underpin their position on monitoring with the results from additional monitoring efforts. Another factor contributing to the increase in monitoring is the requirement for Member States that recently joined the EU to adapt their monitoring systems to comply with the obligations of the European Directives. These are the findings of an International Workshop ('MonNO3' workshop) organised in 2009 by the RIVM together with the Danish National Environmental Research Institute (DMU), the Geological Survey for Denmark and Greenland (GEUS) and LEI, part of Wageningen University and Research Centre. Twelve countries from Northwest and Central Europe participated in the second MonNO3 workshop. The focus was on developments since 2003, the year that the first MonNO3 workshop was held. Similar to the first 'MonNO3' workshop, the second one has also contributed to the exchange of knowledge and information - at the international level - on monitoring the effects of the fertiliser policy. Attention was also paid to the use of monitoring data for purposes other than providing information on the status of and trends in water quality; for example, to use data for underpinning measures to be included in the fertiliser policy. In closing, the participants discussed possible amelioration and expansion of the monitoring networks. Keywords:Ministerie van Economische ZakenLandbouw en Innovati

Study of the Effect of Fossil Organic Carbon on 14C in Groundwater from Hvinningdal, Denmark

From the 16th International Radiocarbon Conference held in Gronigen, Netherlands, June 16-20, 1997.The carbonate hydrochemistry of groundwater from the Hvinningdal aquifer (Denmark) was studied by radiocarbon (accelerator mass spectrometry (AMS)) and delta-13C measurements as a preliminary step towards 14C groundwater dating. The 14C concentrations varied between 30 and 100 percent modern carbon (pMC) in apparent contradiction with tritium (3H) data, which in most cases indicate a post-bomb date. The dilution of 14C can be explained as being due to the combined effect of dissolution of old soil carbonate and oxidation of old organic carbon. The last effect proved to be essential. To calculate this correction the dissolved oxygen concentration was used together with the delta-13C values. The combined corrections bring the 14C concentrations up to post-bomb levels in better agreement with the 3H data.This material was digitized as part of a cooperative project between Radiocarbon and the University of Arizona Libraries.The Radiocarbon archives are made available by Radiocarbon and the University of Arizona Libraries. Contact [email protected] for further information.Migrated from OJS platform February 202

Study of the Effect of Fossil Organic Carbon on 14

From the 16th International Radiocarbon Conference held in Gronigen, Netherlands, June 16-20, 1997.The carbonate hydrochemistry of groundwater from the Hvinningdal aquifer (Denmark) was studied by radiocarbon (accelerator mass spectrometry (AMS)) and delta-13C measurements as a preliminary step towards 14C groundwater dating. The 14C concentrations varied between 30 and 100 percent modern carbon (pMC) in apparent contradiction with tritium (3H) data, which in most cases indicate a post-bomb date. The dilution of 14C can be explained as being due to the combined effect of dissolution of old soil carbonate and oxidation of old organic carbon. The last effect proved to be essential. To calculate this correction the dissolved oxygen concentration was used together with the delta-13C values. The combined corrections bring the 14C concentrations up to post-bomb levels in better agreement with the 3H data.This material was digitized as part of a cooperative project between Radiocarbon and the University of Arizona Libraries.The Radiocarbon archives are made available by Radiocarbon and the University of Arizona Libraries. Contact [email protected] for further information.Migrated from OJS platform February 202

Developments in monitoring the effectiveness of the EU Nitrates Directive Action Programmes : results of the second MonNO3 workshop, 10-11 June 2009

Member States of the European Union are obliged both to monitor the quality of their waters and the effect of their Action Programmes on these waters and to report the results to the European Commission. These monitoring obligations have been interpreted differently by the various countries due to the lack of specific guidelines. Most countries, however, have increased their efforts to monitor water quality the last six years, primarily as a consequence of the discussion between the Member States and the European Commission on how the fertiliser policy should be designed and implemented. Similar to the first ‘MonNO3’ workshop, the second one has also contributed to the exchange of knowledge and information – at the international level – on monitoring the effects of the fertiliser policy. Attention was also paid to the use of monitoring data for purposes other than providing information on the status of and trends in water quality; for example, to use data for underpinning measures to be included in the fertiliser policy. In closing, the participants discussed possible amelioration and expansion of the monitoring networks

Threshold values and management options for nutrients in a catchment of a temperate estuary with poor ecological status

Intensive farming has severe impacts on the chemical status of groundwater and streams and consequently on the ecological status of dependent ecosystems. Eutrophication is a widespread problem in lakes and marine waters. Common problems are hypoxia, algal blooms, fish kills, and loss of water clarity, underwater vegetation, biodiversity and recreational value. In this paper we evaluate the nitrogen (N) and phosphorus (P) concentrations of groundwater and surface water in a coastal catchment, the loadings and sources of N and P, and their effect on the ecological status of an estuary. We calculate the necessary reductions in N and P loadings to the estuary for obtaining a good ecological status, which we define based on the number of days with N and P limitation, and the corresponding stream and groundwater threshold values assuming two different management options. The calculations are performed by the combined use of empirical models and a physically based 3-D integrated hydrological model of the whole catchment. The assessment of the ecological status indicates that the N and P loads to the investigated estuary should be reduced to levels corresponding to 52 and 56% of the current loads, respectively, to restore good ecological status. Model estimates show that threshold total N (TN) concentrations should be in the range of 2.9 to 3.1 mg l<sup>−1</sup> in inlet freshwater (streams) to Horsens estuary and 6.0 to 9.3 mg l<sup>−1</sup> in shallow aerobic groundwater (∼ 27–41 mg l<sup>−1</sup> of nitrate), depending on the management measures implemented in the catchment. The situation for total P (TP) is more complex, but data indicate that groundwater threshold values are not needed. The stream threshold value for TP to Horsens estuary for the selected management options is 0.084 mg l<sup>−1</sup>. Regional climate models project increasing winter precipitation and runoff in the investigated region resulting in increasing runoff and nutrient loads to the Horsens estuary and many other coastal waters if present land use and farming practices continue. Hence, lower threshold values are required in many coastal catchments in the future to ensure good status of water bodies and ecosystems

Assessing steatotic liver function after ischemia-reperfusion injury by in vivo multiphoton imaging of fluorescein disposition

Ischemia-reperfusion injury, a common complication during liver surgery where steatotic livers are more prone to the injury, may become more prevalent in the growing obese population. This study characterizes liver morphology toward understanding changes in subcellular function in steatotic livers exposed to ischemia-reperfusion injury through quantitative description of fluorescein distribution obtained by minimally invasive in vivo multiphoton microscopy using a physiologic pharmacokinetic model. Rats were fed a high-fat diet for 7 days to induce liver steatosis. Partial ischemia was induced after reperfusion for 4 hours, when fluorescein (10mg/kg) was injected intravenously. Liver images, bile, and blood were collected up to 180 minutes after injection. Ischemia-reperfusion injury was associated with an increase in alanine transaminase levels and apoptosis. In addition, steatosis featured lipid droplets and an increase in fluorescein-associated fluorescence observed in hepato-cytes via multiphoton imaging. Analysis of the hepatic concentration-time profiles has suggested that the steatosis-induced increase in fluorescein-associated fluorescence mainly arises by inducing hepatic fluorescein metabolism. The combination of ischemia-reperfusion with steatosis exacerbates these effects further. This was confirmed by fluorescence lifetime imaging microscopy showing a decreased average fluorescence lifetime of the liver, which is indicative of an increased production of the metabolite. Our results show the potential of noninvasive dye imaging for improving our understanding of liver disease induced by subcellular changes in vivo, providing further quantitative measures of metabolic and biliary liver function, and hence extending the qualitative liver function tests now available