Pre-operative interventions (non-surgical and non-pharmacological) for patients with hip or knee osteoarthritis awaiting joint replacement surgery – a systematic review and meta-analysis

SummaryObjectiveTo determine if pre-operative interventions for hip and knee osteoarthritis provide benefit before and after joint replacement.MethodSystematic review with meta-analysis of randomised controlled trials (RCTs) of pre-operative interventions for people with hip or knee osteoarthritis awaiting joint replacement surgery.Standardised mean differences (SMD) were calculated for pain, musculoskeletal impairment, activity limitation, quality of life, and health service utilisation (length of stay and discharge destination). The GRADE approach was used to determine the quality of the evidence.ResultsTwenty-three RCTs involving 1461 participants awaiting hip or knee replacement surgery were identified. Meta-analysis provided moderate quality evidence that pre-operative exercise interventions for knee osteoarthritis reduced pain prior to knee replacement surgery (SMD (95% CI)=0.43 [0.13, 0.73]). None of the other meta-analyses investigating pre-operative interventions for knee osteoarthritis demonstrated any effect. Meta-analyses provided low to moderate quality evidence that exercise interventions for hip osteoarthritis reduced pain (SMD (95% CI)=0.52 [0.04, 1.01]) and improved activity (SMD (95% CI)=0.47 [0.11, 0.83]) prior to hip replacement surgery. Meta-analyses provided low quality evidence that exercise with education programs improved activity after hip replacement with reduced time to reach functional milestones during hospital stay (e.g., SMD (95% CI)=0.50 [0.10, 0.90] for first day walking).ConclusionLow to moderate evidence from mostly small RCTs demonstrated that pre-operative interventions, particularly exercise, reduce pain for patients with hip and knee osteoarthritis prior to joint replacement, and exercise with education programs may improve activity after hip replacement

Sparse Bayesian mass-mapping with uncertainties: hypothesis testing of structure

A crucial aspect of mass-mapping, via weak lensing, is quantification of the uncertainty introduced during the reconstruction process. Properly accounting for these errors has been largely ignored to date. We present results from a new method that reconstructs maximum a posteriori (MAP) convergence maps by formulating an unconstrained Bayesian inference problem with Laplace-type $\ell_1$-norm sparsity-promoting priors, which we solve via convex optimization. Approaching mass-mapping in this manner allows us to exploit recent developments in probability concentration theory to infer theoretically conservative uncertainties for our MAP reconstructions, without relying on assumptions of Gaussianity. For the first time these methods allow us to perform hypothesis testing of structure, from which it is possible to distinguish between physical objects and artifacts of the reconstruction. Here we present this new formalism, demonstrate the method on illustrative examples, before applying the developed formalism to two observational datasets of the Abel-520 cluster. In our Bayesian framework it is found that neither Abel-520 dataset can conclusively determine the physicality of individual local massive substructure at significant confidence. However, in both cases the recovered MAP estimators are consistent with both sets of data

Influence of renal replacement modalities on amikacin population pharmacokinetics in critically ill patients on continuous renal replacement therapy

The objective of this study was to describe amikacin pharmacokinetics (PK) in critically ill patients receiving equal doses (30 ml/kg of body weight/h) of continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodiafiltration (CVVHDF). Patients receiving amikacin and undergoing CVVH or CVVHDF were eligible. Population pharmacokinetic analysis and Monte Carlo simulation were undertaken using the Pmetrics software package for R. Sixteen patients (9 undergoing CVVH, 11 undergoing CVVHDF) and 20 sampling intervals were analyzed. A two-compartment linear model best described the data. Patient weight was the only covariate that was associated with drug clearance. The mean +/- standard deviation parameter estimates were 25.2 +/- 17.3 liters for the central volume, 0.89 +/- 1.17 h(-1) for the rate constant for the drug distribution from the central to the peripheral compartment, 2.38 +/- 6.60 h(-1) for the rate constant for the drug distribution from the peripheral to the central compartment, 4.45 +/- 2.35 liters/h for hemodiafiltration clearance, and 4.69 +/- 2.42 liters/h for hemofiltration clearance. Dosing simulations for amikacin supported the use of high dosing regimens (>= 25 mg/kg) and extended intervals (36 to 48 h) for most patients when considering PK/pharmacodynamic (PD) targets of a maximum concentration in plasma (C-max)/MIC ratio of >= 8 and a minimal concentration o

The IT framework of the European Archive of Historical Earthquake Data (AHEAD)

The European Archive of Historical EArthquake Data (AHEAD) has been developed in the frame of the EC project NERIES and maintained in the frame of the EC project SHARE.AHEAD makes available on the web the result of a networked historical earthquake data research, formalised in terms of studies (papers, reports, macroseismic data points, etc). It provides an updated wealth of data that are unique for many European events in the time-window 1000-1963.A series of IT solutions have been developed in order to support both the research and the networking activities carried out within the building process of AHEAD. The resulting framework is an equally balanced effort in both the back-end and front-end design and implementation, a key feature in a research approach very much human-centred, where the quantity of data is small if compared to terabytes of instrumental data.AHEAD is composed of five mutually dependent data-components: 1) the “Digital Library”, where all the historical earthquake studies are stored and described by bibliographical metadata, 2) the “Consensus Earthquake Inventory”, where the relevant macroseismic data (event date, epicentral area, number of macroseismic data-point, maximum observed intensity) are extrapolated, the best available information are selected and fake earthquakes are highlighted, 3) the “European Macroseismic Database”, where all the available macroseismic data-points (MDPs) are stored, 4) the “Parameters Laboratory”, where earthquakes parameterisation methods are applied to MDPs in order to obtain epicentral locations and magnitudes and 5) the “European Earthquake Catalogue”.The presentation will demonstrate the adopted IT solutions separately for the back-end and the front-end, both for the access-restricted website and the general-purpose implementation designed to be included in the “Earthquake Data Portal”, developed within the EC project NERIES, which targets a much broader scientific community

African American Families\u27 Expectations and Intentions for Mental Health Services

A cross-sectional qualitative descriptive design was used to examine the links among expectations about, experiences with, and intentions toward mental health services. Individual face-to-face interviews were conducted with a purposive sample of 32 African American youth/mothers dyads. Content analysis revealed that positive expectations were linked to positive experiences and intentions, that negative expectations were not consistently linked to negative experiences or intentions, nor were ambivalent expectations linked to ambivalent experiences or intentions. Youth were concerned about privacy breeches and mothers about the harmfulness of psychotropic medication. Addressing these concerns may promote African Americans’ engagement in mental health services

The Theory of Fuzzy Logic and its application to Real Estate Valuation

Fuzzy logic is based on the central idea that in fuzzy sets each element in the set can assume a value from 0 to 1, not just 0 or 1, as in classic set theory. Thus, qualitative characteristics and numerically scaled measures can exhibit gradations in the extent to which they belong to the relevant sets for evaluation. This degree of membership of each element is a measure of the element’s "belonging" to the set, and thus of the precision with which it explains the phenomenon being evaluated. Fuzzy sets can be combined to produce meaningful conclusions, and inferences can be made, given a specified fuzzy input function. The article demonstrates the application of fuzzy logic to an income-producing property, with a resulting fuzzy set output

A validated method for the quantification of fosfomycin on dried plasma spots by HPLC-MS/MS: application to a pilot pharmacokinetic study in humans

Quantification of fosfomycin in the plasma samples of patients is the basis of clinical pharmacokinetic studies from which evidence based dosing regimens can be devised to maximise antibiotic effectiveness against a pathogen. We have developed and validated a LC–MS/MS method to quantify fosfomycin using dried plasma spot sampling. Following HILIC chromatography, fosfomycin and ethylphosphonic acid, used as internal standard, were measured using negative-ion multiple reaction monitoring. The method was linear over the calibration range of 5–2000 mg/L of fosfomycin. Intra-day assay results for dried plasma spot quality control samples at 15.6, 79.9 and 1581 mg/L of fosfomycin had precision of ±4.2, 8.2, and 2.0%, respectively, and accuracy of +3.9, −0.1, and −1.2%, respectively. Recovery of fosfomycin from dried plasma spots was calculated as 83.6% and the dried plasma spot samples were found to be stable stored at room temperature for three months and when stored for four hours at 50 °C. A Bland–Altman plot comparing DPS to plasma sampling found a negative bias of 16.6%, with all but one sample within the mean limits of agreement (−2.6 to 30.6%). Dried plasma spot sampling provides a useful tool for pharmacokinetic research of fosfomycin

Effect of obesity on the population pharmacokinetics of meropenem in critically ill patients

Severe pathophysiological changes in critical illness can lead to dramatically altered antimicrobial pharmacokinetics (PK). The additional effect of obesity on PK potentially increases the challenge for effective dosing. The aim of this prospective study was to describe the population PK of meropenem for a cohort of critically ill patients, including obese and morbidly obese patients. Critically ill patients prescribed meropenem were recruited into the following three body mass index (BMI) groups: nonobese (18.5 to 29.9 kg/m(2)), obese (30.0 to 39.9 kg/m(2)), and morbidly obese (>= 40 kg/m(2)). Serial plasma samples were taken, and meropenem concentrations were determined using a validated chromatographic method. Population PK analysis and Monte Carlo dosing simulations were undertaken with Pmetrics. Nineteen critically ill patients with different BMI categories were enrolled. The patients' mean +/- standard deviation (SD) age, weight, and BMI were 49 +/- 15.9 years, 95 +/- 22.0 kg, and 33 +/- 7.0 kg/m(2), respectively. A two-compartment model described the data adequately. The mean +/- SD parameter estimates for the final covariate model were as follows: clearance (CL), 15.5 +/- 6.0 liters/h; volume of distribution in the central compartment (V-1), 11.7 +/- 5.8 liters; intercompartmental clearance from the central compartment to the peripheral compartment, 25.6 +/- 35.1 liters h(-1); and intercompartmental clearance from the peripheral compartment to the central compartment, 8.32 +/- 12.24 liters h(-1). Higher creatinine clearance (CLCR) was associated with a lower probability of target attainment, with BMI having little effect. Although obesity was found to be associated with an increased V-1, dose adjustment based on CLCR appears to be more important than patient BMI

Beta-Lactam Infusion in Severe Sepsis (BLISS): a prospective, two-centre, open-labelled randomised controlled trial of continuous versus intermittent beta-lactam infusion in critically ill patients with severe sepsis

This study aims to determine if continuous infusion (CI) is associated with better clinical and pharmacokinetic/pharmacodynamic (PK/PD) outcomes compared to intermittent bolus (IB) dosing in critically ill patients with severe sepsis. This was a two-centre randomised controlled trial of CI versus IB dosing of beta-lactam antibiotics, which enrolled critically ill participants with severe sepsis who were not on renal replacement therapy (RRT). The primary outcome was clinical cure at 14 days after antibiotic cessation. Secondary outcomes were PK/PD target attainment, ICU-free days and ventilator-free days at day 28 post-randomisation, 14- and 30-day survival, and time to white cell count normalisation. A total of 140 participants were enrolled with 70 participants each allocated to CI and IB dosing. CI participants had higher clinical cure rates (56 versus 34 %, p = 0.011) and higher median ventilator-free days (22 versus 14 days, p MIC than the IB arm on day 1 (97 versus 70 %, p < 0.001) and day 3 (97 versus 68 %, p < 0.001) post-randomisation. There was no difference in 14-day or 30-day survival between the treatment arms. In critically ill patients with severe sepsis not receiving RRT, CI demonstrated higher clinical cure rates and had better PK/PD target attainment compared to IB dosing of beta-lactam antibiotics. Continuous beta-lactam infusion may be mostly advantageous for critically ill patients with high levels of illness severity and not receiving RRT