Randomized controlled trial of intra-articular ketorolac on pain and inflammation after minor arthroscopic knee surgery.

BACKGROUND: Ketorolac is an effective non-steroidal anti-inflammatory drug, commonly used with local anaesthetics as part of local infiltration analgesia protocols following orthopaedic surgery. However, systemic uptake and drug action may be the major mechanism after local infiltration. The aims of this project were to study the effects of a small, systemically ineffective dose of ketorolac given intra-articularly for post-operative pain and also to study synovial inflammatory biomarkers. We investigated whether ketorolac affects pro-inflammatory biomarkers in an in vitro model, as well. METHODS: In this placebo-controlled, blind, randomized study, we analysed intra-articular ketorolac (5 mg) in ambulatory minor knee surgery patients with moderate or severe pain (n = 44). We assessed post-operative pain intensity (n = 44) and analysed microdialysis samples taken from knee synovial tissue every 20 min (n = 34). We also tested cyclooxygenase-independent effects of ketorolac in synovial cells stimulated by prostaglandin E2 and chondroitin sulphate in vitro. RESULTS: Intra-articular ketorolac (5 mg) administration did not reduce pain or synovial pro-inflammatory cytokines CXCL1, IL-8, and MCP-1, 0-120 min after knee arthroscopy. Female gender was a risk factor for moderate or severe pain (relative risk 1.45, 95% confidence interval 1.04-2.01). Paradoxically, ketorolac increased the release of CXCL1 and IL-8 in prostaglandin E2 and chondroitin sulphate-stimulated synovial cells in vitro. CONCLUSION: Ketorolac prescribed at a low dose intra-articularly does not produce any detectable analgesic effect after minor knee surgery.

Regional frequency analysis of short duration rainfall extremes using gridded daily rainfall data as co-variate.

A regional partial duration series (PDS) model is applied for estimation of intensity duration frequency relationships of extreme rainfalls in Denmark. The model uses generalised least squares regression to relate the PDS parameters to gridded rainfall statistics from a dense network of rain gauges with daily measurements. The Poisson rate is positively correlated to the mean annual precipitation for all durations considered (1 min to 48 hours). The mean intensity can be assumed constant over Denmark for durations up to 1 hour. For durations larger than 1 hour, the mean intensity is significantly correlated to the mean extreme daily precipitation. A Generalised Pareto distribution with a regional constant shape parameter is adopted. Compared to previous regional studies in Denmark, a general increase in extreme rainfall intensity for durations up to 1 hour is found, whereas for larger durations both increases and decreases are seen. A subsample analysis is conducted to evaluate the impacts of non-stationarities in the rainfall data. The regional model includes the non-stationarities as an additional source of uncertainty, together with sampling uncertainty and uncertainty caused by spatial variability.

Microbiota-dependent metabolite trimethylamine-N-oxide is associated with disease severity and survival of patients with chronic heart failure.

OBJECTIVES: Recent metabolomic, experimental and clinical studies have demonstrated that trimethylamine-N-oxide (TMAO), a microbiota-dependent metabolite from dietary phosphatidylcholine and carnitine, is a strong predictor of coronary artery disease (CAD). This finding suggests a link between the gut microbiota and atherosclerosis. The potential impact of TMAO in chronic heart failure (HF) is unknown. We hypothesized that TMAO levels would provide prognostic information about adverse outcomes in chronic HF. DESIGN: Prospective, observational study including 155 consecutive patients with chronic HF. In addition, 100 patients with stable CAD without HF and 33 matched healthy individuals were included as controls. Plasma levels of TMAO and its precursors choline and betaine were measured, and associations with symptoms, aetiology and transplant-free survival in the patients with HF were explored. RESULTS: Plasma levels of TMAO (P = 0.01), choline (P < 0.001) and betaine (P < 0.001) were elevated in patients with chronic HF compared to control subjects, with the highest levels in patients with New York Heart Association (NYHA) classes III and IV. Furthermore, TMAO levels were highest in individuals with ischaemic HF, followed by those with stable CAD and nonischaemic HF. TMAO, but not choline or betaine, was associated with reduced transplant-free survival: approximately 50% of patients in the upper tertile of TMAO levels died or received a heart transplant during 5.2 years of follow-up (unadjusted Cox-regression: hazard ratio 2.24, 95% confidence interval 1.28-3.92, P = 0.005). CONCLUSIONS: TMAO levels were elevated in patients with HF and associated with NYHA class, ischaemic aetiology and adverse outcomes. Future studies should focus on gut microbiota, dietary composition and intestinal dysfunction in relation to TMAO levels and clinical outcome in HF.

Impacts of climate change on rainfall extremes and urban drainage systems: a review.

A review is made of current methods for assessing future changes in urban rainfall extremes and their effects on urban drainage systems, due to anthropogenic-induced climate change. The review concludes that in spite of significant advances there are still many limitations in our understanding of how to describe precipitation patterns in a changing climate in order to design and operate urban drainage infrastructure. Climate change may well be the driver that ensures that changes in urban drainage paradigms are identified and suitable solutions implemented. Design and optimization of urban drainage infrastructure considering climate change impacts and co-optimizing these with other objectives will become ever more important to keep our cities habitable into the future.

Decision strategies for handling the uncertainty of future extreme rainfall under the influence of climate change.

Several extraordinary rainfall events have occurred in Denmark within the last few years. For each event, problems in urban areas occurred as the capacity of the existing drainage systems were exceeded. Adaptation to climate change is necessary but also very challenging as urban drainage systems are characterized by long technical lifetimes and high, unrecoverable construction costs. One of the most important barriers for the initiation and implementation of the adaptation strategies is therefore the uncertainty when predicting the magnitude of the extreme rainfall in the future. This challenge is explored through the application and discussion of three different theoretical decision support strategies: the precautionary principle, the minimax strategy and Bayesian decision support. The reviewed decision support strategies all proved valuable for addressing the identified uncertainties, at best applied together as they all yield information that improved decision making and thus enabled more robust decisions.

Potential future increase in extreme one-hour precipitation events over Europe due to climate change.

In this study the potential increase of extreme precipitation in a future warmer European climate has been examined. Output from the regional climate model (RCM) HIRHAM4 covering Europe has been analysed for two periods, a control period 1961-1990 and a scenario 2071-2100, the latter following the IPCC scenario A2. The model has a resolution of about 12 km, which is unique compared with existing RCM studies that typically operate at 25-50 km scale, and make the results relevant to hydrological phenomena occurring at the spatial scale of the infrastructure designed to drain off rainfall in large urban areas. Extreme events with one- and 24-hour duration were extracted using the Partial Duration Series approach, a Generalized Pareto Distribution was fitted to the data and T-year events for return periods from 2 to 100 years were calculated for the control and scenario period in model cells across Europe. The analysis shows that there will be an increase of the intensity of extreme events generally in Europe; Scandinavia will experience the highest increase and southern Europe the lowest. A 20 year 1-hour precipitation event will for example become a 4 year event in Sweden and a 10 year event in Spain. Intensities for short durations and high return periods will increase the most, which implies that European urban drainage systems will be challenged in the future.