A probabilistic modelling scheme for analysis of long-term failure of cemented femoral joint replacements

Reliable prediction of long-term medical device performance using computer simulation requires consideration of variability in surgical procedure, as well as patient-specific factors. However, even deterministic simulation of long-term failure processes for such devices is time and resource consuming so that including variability can lead to excessive time to achieve useful predictions. This study investigates the use of an accelerated probabilistic framework for predicting the likely performance envelope of a device and applies it to femoral prosthesis loosening in cemented hip arthroplasty.
A creep and fatigue damage failure model for bone cement, in conjunction with an interfacial fatigue model for the implant–cement interface, was used to simulate loosening of a prosthesis within a cement mantle. A deterministic set of trial simulations was used to account for variability of a set of surgical and patient factors, and a response surface method was used to perform and accelerate a Monte Carlo simulation to achieve an estimate of the likely range of prosthesis loosening. The proposed framework was used to conceptually investigate the influence of prosthesis selection and surgical placement on prosthesis migration.
Results demonstrate that the response surface method is capable of dramatically reducing the time to achieve convergence in mean and variance of predicted response variables. A critical requirement for realistic predictions is the size and quality of the initial training dataset used to generate the response surface and further work is required to determine the recommendations for a minimum number of initial trials. Results of this conceptual application predicted that loosening was sensitive to the implant size and femoral width. Furthermore, different rankings of implant performance were predicted when only individual simulations (e.g. an average condition) were used to rank implants, compared with when stochastic simulations were used. In conclusion, the proposed framework provides a viable approach to predicting realistic ranges of loosening behaviour for orthopaedic implants in reduced timeframes compared with conventional Monte Carlo simulations.

The Role of Micronutrients in Heart Failure

Heart failure is a common condition in the Western world, particularly among elderly persons and with an ever-aging population, the incidence is expected to increase. Diet in the setting of heart failure is important--patients with this condition are advised to consume a low-salt diet and monitor their weight closely. Nutritional status of patients with heart failure also is important--those with poor nutritional status tend to have a poor long-term prognosis. A growing body of evidence suggests an association between heart failure and micronutrient status. Reversible heart failure has been described as a consequence of severe thiamine and selenium deficiency. However, contemporary studies suggest that a more subtle relationship may exist between micronutrients and heart failure. This article reviews the existing literature linking heart failure and micronutrients, examining studies that investigated micronutrient intake, micronutrient status, and the effect of micronutrient supplementation in patients with heart failure, and focusing particularly on vitamin A, vitamin C, vitamin E, thiamine, other B vitamins, vitamin D, selenium, zinc, and copper.

Deconstructing national leadership: Politicians’ accounts of electoral success and failure in the Irish Lisbon Treaty referenda

The Self Categorization approach to national leadership proposes that leaders rhetorically construct national identity as essentialized and inevitable in order to consensualize and mobilize the population. In contrast, discursive studies have demonstrated how national politicians flexibly construct the nation to manage their own accountability in local interactions, though this in turn has neglected broader leadership processes. The present paper brings both approaches together to examine how and when national politicians construct versions of national identity in order to account for their failure as well as success in mobilizing the electorate. Eight semi-structured conversational style interviews were conducted with a strategic sample of eight leading Irish politicians on the subject of the 2008/2009 Irish Lisbon Treaty referenda. Using a Critical Discourse Psychology approach, the hegemonic repertoire of the ‘settled will’
of the informed and consensualized Irish nation was identified across all interviews. Politicians either endorsed the ‘settled will’ repertoire as evidence of their successful leadership, or rejected the repertoire by denying the rationality or unity of the populace to account for their failure. Our results suggest national identity is only constructed as essentialized and inevitable to the extent that it serves a strategic political purpose.

Donor ABCB1 Variant Associates with Increased Risk for Kidney Allograft Failure

The impact of variation within genes responsible for the disposition and metabolism of calcineurin inhibitors (CNIs) on clinical outcomes in kidney transplantation is not well understood. Furthermore, the potential influence of donor, rather than recipient, genotypes on clinical endpoints is unknown. Here, we investigated the associations between donor and recipient gene variants with outcome among 4471 white, CNI-treated kidney transplant recipients. We tested for 52 single-nucleotide polymorphisms (SNPs) across five genes: CYP3A4, CYP3A5, ABCB1 (MDR1; encoding P-glycoprotein), NR1I2 (encoding the pregnane X receptor), and PPIA (encoding cyclophilin). In a discovery cohort of 811 patients from Birmingham, United Kingdom, kidney donor CC genotype at C3435T (rs1045642) within ABCB1, a variant known to alter protein expression, was associated with an increased risk for long-term graft failure compared with non-CC genotype (hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.20-2.40; P=0.003). No other donor or recipient SNPs were associated with graft survival or mortality. We validated this association in 675 donors from Belfast, United Kingdom (HR, 1.68; 95% CI, 1.21-2.32; P=0.002), and in 2985 donors from the Collaborative Transplant Study (HR, 1.84; 95% CI, 1.08-3.13; P=0.006). In conclusion, these data suggest that an ABCB1 variant known to alter protein expression represents an attractive candidate for future study and risk stratification in kidney transplantation.

Pharmacokinetics of flosequinan in patients with heart failure

The pharmacokinetics of flosequinan were studied in a group of 18 patients with chronic cardiac failure.