Patient-specific image-based computer simulation for theprediction of valve morphology and calcium displacement after TAVI with the Medtronic CoreValve and the Edwards SAPIEN valve

AIMS: Our aim was to validate patient-specific software integrating baseline anatomy and biomechanical properties of both the aortic root and valve for the prediction of valve morphology and aortic leaflet calcium displacement after TAVI. METHODS AND RESULTS: Finite element computer modelling was performed in 39 patients treated with a Medtronic CoreValve System (MCS; n=33) or an Edwards SAPIEN XT (ESV; n=6). Quantitative axial frame morphology at inflow (MCS, ESV) and nadir, coaptation and commissures (MCS) was compared between multislice computed tomography (MSCT) post TAVI and a computer model as well as displacement of the aortic leaflet calcifications, quantified by the distance between the coronary ostium and the closest calcium nodule. Bland-Altman analysis revealed a strong correlation between the observed (MSCT) and predicted frame dimensions, although small differences were detected for, e.g., Dmin at the inflow (mean±SD MSCT vs. MODEL: 21.6±2.4 mm vs. 22.0±2.4 mm; difference±SD: -0.4±1.3 mm, p<0.05) and Dmax (25.6±2.7 mm vs. 26.2±2.7 mm; difference±SD: -0.6±1.0 mm, p<0.01). The observed and predicted calcium displacements were highly correlated for the left and right coronary ostia (R2=0.67 and R2=0.71, respectively p<0.001). CONCLUSIONS: Dedicated software allows accurate prediction of frame morphology and calcium displacement after valve implantation, which may help to improve outcome

Cost-utility of transcatheter aortic valve implantation for inoperable patients with severe aortic stenosis treated by medical management: a UK cost-utility analysis based on patient-level data from the ADVANCE study.

OBJECTIVE: To use patient-level data from the ADVANCE study to evaluate the cost-effectiveness of transcatheter aortic valve implantation (TAVI) compared to medical management (MM) in patients with severe aortic stenosis from the perspective of the UK NHS. METHODS: A published decision-analytic model was adapted to include information on TAVI from the ADVANCE study. Patient-level data informed the choice as well as the form of mathematical functions that were used to model all-cause mortality, health-related quality of life and hospitalisations. TAVI-related resource use protocols were based on the ADVANCE study. MM was modelled on publicly available information from the PARTNER-B study. The outcome measures were incremental cost-effectiveness ratios (ICERs) estimated at a range of time horizons with benefits expressed as quality-adjusted life-years (QALY). Extensive sensitivity/subgroup analyses were undertaken to explore the impact of uncertainty in key clinical areas. RESULTS: Using a 5-year time horizon, the ICER for the comparison of all ADVANCE to all PARTNER-B patients was £13 943 per QALY gained. For the subset of ADVANCE patients classified as high risk (Logistic EuroSCORE >20%) the ICER was £17 718 per QALY gained). The ICER was below £30 000 per QALY gained in all sensitivity analyses relating to choice of MM data source and alternative modelling approaches for key parameters. When the time horizon was extended to 10 years, all ICERs generated in all analyses were below £20 000 per QALY gained. CONCLUSION: TAVI is highly likely to be a cost-effective treatment for patients with severe aortic stenosis

Comparison of three different application routes of butyrate to improve colonic anastomotic strength in rats

Despite extensive research, anastomotic leakage (AL) remains one of the most dreaded complications after colorectal surgery. Since butyrate enemas are known to enhance anastomotic healing, several administration routes have been explored in this study. Three intraluminal approaches involving butyrate were investigated: (1) butyrin-elucidating patch, (2) a single injection of hyaluronan-butyrate (HA-But) prior to construction of the proximal anastomosis and (3) rectal hyaluronan-butyrate (HA-But) enemas designed for distal anastomoses. The main outcome was AL and secondary outcomes were bursting pressure, histological analysis of the anastomosis, zymography to detect MMP activity and qPCR for gene expression of MMP2, MMP9, MUC2 and TFF3. RESULTS: Neither the patches nor the injections led to a reduction of AL in experiments 1 and 2. In experiment 3, a significant reduction of AL was accomplished with the (HA-But) enema compared to the control group together with a higher bursting pressure. Histological analysis detected only an increased inflammation in experiment 2 in the hyaluronan injection group compared to the control group. No other differences were found regarding wound healing. Zymography identified a decreased proenzyme of MMP9 when HA-But was administered as a rectal enema. qPCR did not show any significant differences between groups in any experiment. CONCLUSION: Butyrate enemas are effective in the enhancement of colonic anastomosis. Enhanced butyrate-based approaches designed to reduce AL in animal models for both proximal and distal anastomoses were not more effective than were butyrate enemas alone. Further research should focus on how exogenous butyrate can improve anastomotic healing after gastrointestinal surgery

Isolated thumb carpometacarpal joint dislocation: a case report and review of the literature

<p>Abstract</p> <p>Background</p> <p>Isolated thumb carpometacarpal dislocation is a rare injury pattern and the optimal treatment option is still controversial.</p> <p>Case Description</p> <p>We present a 27-year-old basketball player who underwent an isolated dorsal dislocation of the thumb carpometacarpal joint after a fall. The dislocation was successfully reduced by closed means but the joint was found to be grossly unstable. Due to inherent instability, repair of the ruptured dorsoradial ligament and joint capsule was performed.</p> <p>The ligament was detached from its proximal insertion into trapezium and subsequently stabilized via suture anchors. The torn capsule was repaired in an end-to-end fashion and immobilization of the joint was applied for 6 weeks.</p> <p>Results</p> <p>At 3-year follow up evaluation the patient was pain free and returned to his previous level of activity. No restriction of carpometacrpal movements or residual instability was noticed. Radiographic examination showed normal joint alignment and no signs of subluxation or early osteoarthritis.</p> <p>Conclusion</p> <p>Surgical stabilization of the dorsal capsuloligamentous complex may be considered the selected treatment option in isolated carpometacarpal joint dislocations, that remain unstable after closed reduction in young and high demand patients.</p> <p><b>Level of Clinical Evidence: </b>Level IV</p

Mycophenolate mofetil versus azathioprine for prevention of acute rejection in renal transplantation (MYSS): a randomised trial.

BACKGROUND: Mycophenolate mofetil has replaced azathioprine in immunosuppression regimens worldwide to prevent graft rejection. However, evidence that its antirejection activity is better than that of azathioprine has been provided only by registration trials with an old formulation of ciclosporin and steroid. We aimed to compare the antirejection activity of these two drugs with a new formulation of ciclosporin. METHODS: The mycophenolate steroids sparing multicentre, prospective, randomised, parallel-group trial compared acute rejections and adverse events in recipients of cadaver-kidney transplants over 6-month treatment with mycophenolate mofetil or azathioprine along with ciclosporin microemulsion (Neoral) and steroids (phase A), and over 15 more months without steroids (phase B). The primary endpoint was occurrence of acute rejection episodes. Analysis was by intention to treat. FINDINGS: 168 patients per group entered phase A. 56 (34%) assigned mycophenolate mofetil and 58 (35%) assigned azathioprine had clinical rejections (risk reduction [RR] on mycophenolate mofetil compared with azathioprine 13.7% [95% CI -25.7% to 40.7%], p=0.44). 88 patients in the mycophenolate mofetil group and 89 in the azathioprine group entered phase B. 14 (16%) taking mycophenolate mofetil and 11 (12%) taking azathioprine had clinical rejections (RR -16.2%, [-157.5% to 47.5%], p=0.71). Average per-patient costs of mycophenolate mofetil treatment greatly exceeded those of azathioprine (phase A 2665 Euros [SD 586] vs Euros 184 [62]; phase B 5095 Euros [2658] vs 322 Euros [170], p<0.0001 for both). INTERPRETATION: In recipients of cadaver kidney-transplants given ciclosporin microemulsion, mycophenolate mofetil offers no advantages over azathioprine in preventing acute rejections and is about 15 times more expensive. Standard immunosuppression regimens for transplantation should perhaps include azathioprine rather than mycophenolate mofetil, at least for kidney graft

Cauchy's infinitesimals, his sum theorem, and foundational paradigms

Cauchy's sum theorem is a prototype of what is today a basic result on the convergence of a series of functions in undergraduate analysis. We seek to interpret Cauchy's proof, and discuss the related epistemological questions involved in comparing distinct interpretive paradigms. Cauchy's proof is often interpreted in the modern framework of a Weierstrassian paradigm. We analyze Cauchy's proof closely and show that it finds closer proxies in a different modern framework. Keywords: Cauchy's infinitesimal; sum theorem; quantifier alternation; uniform convergence; foundational paradigms.Comment: 42 pages; to appear in Foundations of Scienc

Cost-effectiveness of an exercise program during pregnancy to prevent gestational diabetes: Results of an economic evaluation alongside a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>The prevalence of gestational diabetes mellitus (GDM) is increasing worldwide. GDM and the risks associated with GDM lead to increased health care costs and losses in productivity. The objective of this study is to evaluate whether the FitFor2 exercise program during pregnancy is cost-effective from a societal perspective as compared to standard care.</p> <p>Methods</p> <p>A randomised controlled trial (RCT) and simultaneous economic evaluation of the FitFor2 program were conducted. Pregnant women at risk for GDM were randomised to an exercise program to prevent high maternal blood glucose (n = 62) or to standard care (n = 59). The exercise program consisted of two sessions of aerobic and strengthening exercises per week. Clinical outcome measures were maternal fasting blood glucose levels, insulin sensitivity and infant birth weight. Quality of life was measured using the EuroQol 5-D and quality-adjusted life-years (QALYs) were calculated. Resource utilization and sick leave data were collected by questionnaires. Data were analysed according to the intention-to-treat principle. Missing data were imputed using multiple imputations. Bootstrapping techniques estimated the uncertainty surrounding the cost differences and incremental cost-effectiveness ratios.</p> <p>Results</p> <p>There were no statistically significant differences in any outcome measure. During pregnancy, total health care costs and costs of productivity losses were statistically non-significant (mean difference €1308; 95%CI €-229 - €3204). The cost-effectiveness analyses showed that the exercise program was not cost-effective in comparison to the control group for blood glucose levels, insulin sensitivity, infant birth weight or QALYs.</p> <p>Conclusion</p> <p>The twice-weekly exercise program for pregnant women at risk for GDM evaluated in the present study was not cost-effective compared to standard care. Based on these results, implementation of this exercise program for the prevention of GDM cannot be recommended.</p> <p>Trial registration</p> <p>NTR1139</p

PCR-GLOBWB 2: a 5 arcmin global hydrological and water resources model

We present PCR-GLOBWB 2, a global hydrology and water resources model. Compared to previous versions of PCR-GLOBWB, this version fully integrates water use. Sector-specific water demand, groundwater and surface water withdrawal, water consumption, and return flows are dynamically calculated at every time step and interact directly with the simulated hydrology. PCR-GLOBWB 2 has been fully rewritten in Python and PCRaster Python and has a modular structure, allowing easier replacement, maintenance, and development of model components. PCR-GLOBWB 2 has been implemented at 5 arcmin resolution, but a version parameterized at 30 arcmin resolution is also available. Both versions are available as open-source codes on https://github.com/UU-Hydro/PCR-GLOBWB_model (Sutanudjaja et al., 2017a). PCR-GLOBWB 2 has its own routines for groundwater dynamics and surface water routing. These relatively simple routines can alternatively be replaced by dynamically coupling PCR-GLOBWB 2 to a global two-layer groundwater model and 1-D–2-D hydrodynamic models. Here, we describe the main components of the model, compare results of the 30 and 5 arcmin versions, and evaluate their model performance using Global Runoff Data Centre discharge data. Results show that model performance of the 5 arcmin version is notably better than that of the 30 arcmin version. Furthermore, we compare simulated time series of total water storage (TWS) of the 5 arcmin model with those observed with GRACE, showing similar negative trends in areas of prevalent groundwater depletion. Also, we find that simulated total water withdrawal matches reasonably well with reported water withdrawal from AQUASTAT, while water withdrawal by source and sector provide mixed results

Effectiveness of a stepped-care intervention to prevent major depression in patients with type 2 diabetes mellitus and/or coronary heart disease and subthreshold depression: A pragmatic cluster randomized controlled trial

Purpose Given the public health significance of poorly treatable co-morbid major depressive disorders (MDD) among patients with type 2 diabetes mellitus (DM2) and coronary heart disease (CHD), we need to investigate whether strategies to prevent the development of major depression could reduce its burden of disease. We therefore evaluated the effectiveness of a stepped-care program for subthreshold depression in comparison with usual care in patients with DM2 and/or CHD. Methods A cluster randomized controlled trial, with 27 primary care centers serving as clusters. A total of 236 DM2 and/or CHD patients with subthreshold depression (nine item Patient Health Questionnaire (PHQ-9) score ≥ 6, no current MDD according to DSM-IV criteria) were allocated to the intervention group (N = 96) or usual care group (n = 140). The stepped-care program was delivered by trained practice nurses during one year and consisted of four sequential treatment steps: watchful waiting, guided self-help, problem solving treatment and referral to the general practitioner. The primary outcome was the 12-month cumulative incidence of MDD as measured with the Mini International Neuropsychiatric Interview (MINI). Secondary outcomes included severity of depression (measured by PHQ-9) at 3, 6, 9 and 12 months. Results Of 236 patients (mean age, 67,5 (SD 10) years; 54.7% men), 210 (89%) completed the MINI at 12 months. The cumulative incidence of MDD was 9 of 89 (10.1%) participants in the intervention group and 12 of 121 (9.9%) participants in the usual care group. We found no statistically significant overall effect of the intervention (OR = 1.21; 95% confidence interval (0.12 to 12.41)) and there were no statistically significant differences in the course or severity of depressive symptoms between the two groups. Conclusions This study suggest that Step-Dep was not more effective in preventing MDD than usual care in a primary care population with DM2 and/or CHD and subthreshold depression

Global assessment of the carbon–water tradeoff of dry cooling for thermal power generation

Water scarcity and climate change are dual challenges that could potentially threaten energy security. Yet, integrated water–carbon management frameworks coupling diverse water- and carbon-mitigation technologies at high spatial heterogeneity are largely underdeveloped. Here we build a global unit-level framework to investigate the CO2 emission and energy penalty due to the deployment of dry cooling—a critical water mitigation strategy—together with alternative water sourcing and carbon capture and storage under climate scenarios. We find that CO2 emission and energy penalty for dry cooling units are location and climate specific (for example, 1–15% of power output), often demonstrating notably faster efficiency losses than rising temperature, especially under the high climate change scenario. Despite energy and CO2 penalties associated with alternative water treatment and carbon capture and storage utilization, increasing wastewater and brine water accessibility provide potential alternatives to dry cooling for water scarcity alleviation, whereas CO2 storage can help to mitigate dry cooling-associated CO2 emission tradeoffs when alternative water supply is insufficient. By demonstrating an integrative planning framework, our study highlights the importance of integrated power sector planning under interconnected dual water–carbon challenges