Phospho-regulation, nucleotide binding and ion access control in potassium-chloride cotransporters.

Potassium-coupled chloride transporters (KCCs) play crucial roles in regulating cell volume and intracellular chloride concentration. They are characteristically inhibited under isotonic conditions via phospho-regulatory sites located within the cytoplasmic termini. Decreased inhibitory phosphorylation in response to hypotonic cell swelling stimulates transport activity, and dysfunction of this regulatory process has been associated with various human diseases. Here, we present cryo-EM structures of human KCC3b and KCC1, revealing structural determinants for phospho-regulation in both N- and C-termini. We show that phospho-mimetic KCC3b is arrested in an inward-facing state in which intracellular ion access is blocked by extensive contacts with the N-terminus. In another mutant with increased isotonic transport activity, KCC1Δ19, this interdomain interaction is absent, likely due to a unique phospho-regulatory site in the KCC1 N-terminus. Furthermore, we map additional phosphorylation sites as well as a previously unknown ATP/ADP-binding pocket in the large C-terminal domain and show enhanced thermal stabilization of other CCCs by adenine nucleotides. These findings provide fundamentally new insights into the complex regulation of KCCs and may unlock innovative strategies for drug development.

Impact of including productivity costs in economic analyses of vaccines for C. difficile infections and infant respiratory syncytial virus, in a UK setting.

OBJECTIVES: It has been estimated that vaccines can accrue a relatively large part of their value from patient and carer productivity. Yet, productivity value is not commonly or consistently considered in health economic evaluations of vaccines in several high-income countries. To contribute to a better understanding of the potential impact of including productivity value on the expected cost-effectiveness of vaccination, we illustrate the extent to which the incremental costs would change with and without productivity value incorporated. METHODS: For two vaccines currently under development, one against Cloistridioides difficile (C. difficile) infection and one against respiratory syncytial disease (RSV), we estimated their incremental costs with and without productivity value included and compared the results. RESULTS: In this analysis, reflecting a UK context, a C. difficile vaccination programme would prevent £12.3 in productivity costs for every person vaccinated. An RSV vaccination programme would prevent £49 in productivity costs for every vaccinated person. CONCLUSIONS: Considering productivity costs in future cost-effectiveness analyses of vaccines for C. difficile and RSV will contribute to better-informed reimbursement decisions from a societal perspective.

Ongoing outbreak of hepatitis A associated with sexual transmission among men who have sex with men, Portugal, October 2023 to April 2024.

An outbreak of hepatitis A is ongoing in Portugal, with 71 confirmed cases from 7 October 2023 to 24 April 2024. Most cases are male, aged 18-44 years, with many identifying as men who have sex with men (MSM) and reported as suspected sexual transmission. Phylogenetic analysis identified the subgenotype IA, VRD 521-2016 strain, last observed in an MSM-associated multi-country outbreak in 2016 to 2018. We wish to alert colleagues in other countries to investigate potential similar spread.

Depth Control of an Underwater Sensor Platform: Comparison between Variable Buoyancy and Propeller Actuated Devices.

Underwater long-endurance platforms are crucial for continuous oceanic observation, allowing for sustained data collection from a multitude of sensors deployed across diverse underwater environments. They extend mission durations, reduce maintenance needs, and significantly improve the efficiency and cost-effectiveness of oceanographic research endeavors. This paper investigates the closed-loop depth control of actuation systems employed in underwater vehicles, focusing on the energy consumption of two different mechanisms: variable buoyancy and propeller actuated devices. Using a prototype previously developed by the authors, this paper presents a detailed model of the vehicle using both actuation solutions. The proposed model, although being a linear-based one, accounts for several nonlinearities that are present such as saturations, sensor quantization, and the actuator brake model. Also, it allows a simple estimation of the energy consumption of both actuation solutions. Based on the developed models, this study then explores the intricate interplay between energy consumption and control accuracy. To this end, several PID-based controllers are developed and tested in simulation. These controllers are used to evaluate the dynamic response and power requirements of variable buoyancy systems and propeller actuated devices under various operational conditions. Our findings contribute to the optimization of closed-loop depth control strategies, offering insights into the trade-offs between energy efficiency and system effectiveness in diverse underwater applications.

The role of transurethral resection of prostate (TURP) in patients with underactive bladder: 12 months follow-up in different grades of detrusor contractility.

INTRODUCTION AND OBJECTIVE: Male detrusor underactivity (DUA) definition remains controversial and no effective treatment is consolidated. Transurethral resection of the prostate (TURP) is one of the cornerstones surgical treatments recommended in bladder outlet obstruction (BOO). However, the role of prostatic surgery in male DUA is not clear. The primary endpoint was the clinical and voiding improvement based on IPSS and the maximum flow rate in uroflowmetry (Qmax) within 12 months. MATERIALS AND METHODS: We analyzed an ongoing prospective database that embraces benign prostata hyperplasia (BPH) male patients with lower urinary tract symptoms who have undergone to TURP. All patients were evaluated pre and postoperatively based on IPSS questionnaires, prostate volume measured by ultrasound, postvoid residual urine volume (PVR), Prostate Specific Antigen measurement and urodynamic study (UDS) before the procedure. After surgery, all patients were evaluated at 1-, 3-, 6- and 12-months. Patients were categorized in 3 groups: Group 1-Detrusor Underactive (Bladder Contractility Index (BCI) [BCI] < 100 and BOO index [BOOI] < 40); Group 2-Detrusor Underactive and BOO (BCI < 100 and BOOI ≥ 40); Group 3-BOO (BCI ≥ 100 and BOOI ≥ 0). RESULTS: It was included 158 patients underwent monopolar or bipolar TURP since November 2015 to March 2021. According to UDS, patients were categorized in: group 1 (n = 39 patients); group 2 (n = 41 patients); group 3 (n = 77 patients). Preoperative IPSS was similar between groups (group 1-24.9 ± 6.33; group 2-24.8 ± 7.33; group 3-24.5 ± 6.23). Qmax was statistically lower in the group 2 (group 1-5.43 ± 3.69; group 2-3.91 ± 2.08; group 3-6.3 ± 3.18) as well as greater PVR. The 3 groups presented similar outcomes regard to IPSS score during the follow-up. There was a significant increase in Qmax in the 3 groups. However, group 1 presented the lowest Qmax improvement. CONCLUSION: There were different objective outcomes depending on the degree of DUA at 12 months follow-up. Patients with DUA had similar IPSS improvement. However, DUA patients had worst Qmax improvement than men with normal bladder contraction.

Matching-Adjusted Indirect Comparisons of Lorlatinib Versus Chemotherapy for Patients With Second-Line or Later Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer.

OBJECTIVES: This study aimed to compare the relative efficacy of lorlatinib, an anaplastic lymphoma kinase-tyrosine kinase inhibitor, with chemotherapy, for patients with second-line or later advanced anaplastic lymphoma kinase-positive non-small cell lung cancer. The endpoints of interest were overall survival (OS) and progression-free survival (PFS). METHODS: Evidence for lorlatinib was informed by the single-arm phase I/II trial B7461001. A systematic literature review (SLR) was performed to identify OS and PFS data for chemotherapy. Unanchored matching-adjusted indirect comparisons (MAICs) between lorlatinib and chemotherapy (pemetrexed/docetaxel, platinum-based, or systemic therapy) were performed. RESULTS: The SLR identified 3 relevant studies reporting PFS. Lorlatinib was associated with a significant decrease in the hazard of progression versus the 2 types of chemotherapy assessed. For PFS, the MAIC of lorlatinib versus the combined treatment arm of docetaxel or pemetrexed resulted in an adjusted hazard ratio (HR) of 0.22 (95% confidence interval [CI] 0.15-0.31). When lorlatinib was compared with platinum-based chemotherapy through an MAIC, the adjusted HR for PFS was 0.40 (95% CI 0.29-0.55). An exploratory comparison was performed for OS with evidence for systemic therapy (assumed equivalent to chemotherapy) not identified in the SLR. Lorlatinib provided a significant decrease in hazard of death (OS) versus systemic therapy, with HRs ranging from 0.12 (95% CI 0.05-0.27) to 0.43 (95% CI 0.27-0.60). CONCLUSIONS: Lorlatinib demonstrated a significant improvement in PFS compared with chemotherapy, although limitations in the analyses were identified. The evidence informing OS comparisons was highly limited but suggested benefit of lorlatinib compared with systemic therapy.

Periradicular surgery: a longitudinal registry study of ten-year outcomes and factors predictive of post-surgical extraction.

AIM: This historical prospective cohort study of the adult population of Sweden is based on data from a national registry: the primary aim was to evaluate the long-term survival of teeth after periradicular surgery. A secondary aim was to identify factors predictive of extraction within 10 years of registration of periradicular surgery. METHODOLOGY: The cohort consisted of all individuals who had undergone periradicular surgery to treat apical periodontitis, as reported to the Swedish Social Insurance Agency (SSIA) during 2009. The cohort was followed until December 31, 2020. Subsequent registrations of extractions were collected for Kaplan-Meier survival analyses and survival tables. The patients' sex, age, dental service provider and tooth group were also retrieved from SSIA. Only one tooth per individual was included in the analyses. Multivariable regression analysis was used and P < 0.05 was considered statistically significant. The reporting guidelines STROBE and PROBE were followed. RESULTS: After data cleaning, and exclusion of 157 teeth, 5 622 teeth/individuals remained for analysis. The mean age of the individuals at the time of the periradicular surgery was 60.5 years (range 20-97, standard deviation 13.31); 55% were women. At the end of the follow-up, that is, up to 12 years, a total of 34.1% of the teeth had been reported as extracted. The multivariate logistic regression analysis, based on follow-up data at 10 years after registration of the periradicular surgery, included 5 548 teeth, of which 1 461 (26.3%) had been extracted. Significant associations between the independent variables tooth group and dental care setting (both P < 0.001) and the dependent variable extraction were found. The highest odds ratio (OR) for extraction applied to tooth group: compared to maxillary incisors and canines, mandibular molars were at greatest risk of extraction (OR 2.429, confidence interval 1.975-2.987, P < 0.001). CONCLUSIONS: After periradicular surgery in predominantly elderly people in Sweden, approximately three quarters of the teeth are retained over a 10-year period. The type of tooth is associated with extraction: mandibular molars are at greater risk of extraction than maxillary incisors and canines.

Different regulatory framework for medical devices and drugs in the European Union: Impact on clinical research and health technology assessments.

OBJECTIVES: Understanding whether the regulatory framework in the European Union creates different standards for medical devices and drugs, assessing whether there is evidence on the impact of those standards on clinical and HTA research, and reflecting on findings in order to propose legislative changes for promoting a more efficient allocation of resources in the healthcare systems. METHODS: Reviewing and comparing the legal framework for the approval of medical devices and drugs in the EU, with a particular focus on the changes brought by Regulation (EU) 2017/745. Investigating the available information on manufacturer sponsored clinical studies and HTA-supported recommendations for medical devices and drugs. RESULTS: The review of the legislation identified different standards for approval of devices and drugs on their quality, safety, and performance/efficacy dimensions and fewer manufacturer sponsored clinical studies and HTA-supported recommendations for medical devices versus drugs. CONCLUSIONS: Policy changes could be implemented in order to promote an integrated evidence-based assessment system for a better allocation of resources in healthcare, namely: a consensual classification of medical devices from an HTA perspective, which could be used as a guide for generating outcomes in clinical investigation, and the adoption of conditional coverage practices including mandatory post-approval evidence development for performing periodic technology assessments.

Clinical and Urodynamic results of the Argus T® sling in moderate and severe male stress urinary incontinence after radical prostatectomy - a 5 year prospective study.

PURPOSE: Sling as a therapeutic option for male stress urinary incontinence (SUI) has been reviewed in the last two decades, as it is a relatively simpliest surgery compared to artificial urinary sphincter and has the ability to modulate urethral compression. This study aims to evaluate the efficacy, rate of complications, quality of life and the effects on bladder emptying of the Argus T® compressive and ajustable sling in moderate and severe male SUI treatment. MATERIALS AND METHODS: Men eligible for stress urinary incontinence treatment after radical prostatectomy were recruited and prospectively evaluated, from March 2010 to November 2016. It was selected outpatient men with moderate and severe SUI, after 12 months of radical prostatectomy, who have failed conservative treatment. All patients had a complete clinical and urodynamic pre and post treatment evaluation, by means of clinical history, physical examination, urine culture, 1-hour pad test and ICIq-SF questionnaire. The UDS was performed after 12, 18 and 24 months postoperatively. RESULTS: Thirty-seven men underwent sling surgery, 19 patients (51.4%) with moderate and 18 (48.6%) with severe SUI. The minimum follow-up time was 5 years. Overall, we had a success rate of 56.7% at 60 months follow-up. After surgery, we did not observe significant changes in the urodynamic parameters evaluated during the follow-up. No patient had urodynamic bladder outlet obstruction (BOO) after sling implantation. Readjustment of the Argus T® sling was performed in 16 (41%) of the patients and 51% of the patients reported some adverse event. CONCLUSION: We demonstrate a long-term efficacy and safety of Sling Argus T® as an alternative to moderate and severe male SUI treatment. Furthermore, in our study bulbar urethra compression does not lead to bladder outlet obstruction.

Ceramide-1-Phosphate as a Potential Regulator of the Second Sodium Pump from Kidney Proximal Tubules by Triggering Distinct Protein Kinase Pathways in a Hierarchic Way.

Kidney proximal tubules are a key segment in the reabsorption of solutes and water from the glomerular ultrafiltrate, an essential process for maintaining homeostasis in body fluid compartments. The abundant content of Na+ in the extracellular fluid determines its importance in the regulation of extracellular fluid volume, which is particularly important for different physiological processes including blood pressure control. Basolateral membranes of proximal tubule cells have the classic Na+ + K+-ATPase and the ouabain-insensitive, K+-insensitive, and furosemide-sensitive Na+-ATPase, which participate in the active Na+ reabsorption. Here, we show that nanomolar concentrations of ceramide-1 phosphate (C1P), a bioactive sphingolipid derived in biological membranes from different metabolic pathways, promotes a strong inhibitory effect on the Na+-ATPase activity (C1P50 ≈ 10 nM), leading to a 72% inhibition of the second sodium pump in the basolateral membranes. Ceramide-1-phosphate directly modulates protein kinase A and protein kinase C, which are known to be involved in the modulation of ion transporters including the renal Na+-ATPase. Conversely, we did not observe any effect on the Na+ + K+-ATPase even at a broad C1P concentration range. The significant effect of ceramide-1-phosphate revealed a new potent physiological and pathophysiological modulator for the Na+-ATPase, participating in the regulatory network involving glycero- and sphingolipids present in the basolateral membranes of kidney tubule cells.

Current Microscopy Strategies to Image Fungal Vesicles: From the Intracellular Trafficking and Secretion to the Inner Structure of Isolated Vesicles.

Extracellular vesicles (EVs) are nano-sized structures that play important roles in a variety of biological processes among members of the Eukaryota domain. They have been studied since the 1940s and a broader use of different microscopy techniques to image either isolated vesicles or vesicles within the intracellular milieu (trafficking) has been limited by their nanometric size, usually below the resolution limit of most standard light microscopes. The development of genetically encoded fluorescent proteins and fluorescent probes able to switch between "on" and "off" states, as well the improvement in computer-assisted microscopy, photon detector devices, illumination designs, and imaging strategies in the late Twentieth century, boosted the use of light microscopes to provide structural and functional information at the sub-diffraction resolution, taking advantage of a nondestructive analytical probe such light, and opening new possibilities in the study of life at the nanoscale. As well, traditional and novel electron microscopy techniques have been widely used in the characterization of subcellular compartments, either isolated or in situ, providing a comprehensive understanding of their functional role in many cellular processes. Here, we present basic aspects of some of these techniques that have already been applied and their potential application to the study of fungal vesicles.

A Scheduling Scheme for Improving the Performance and Security of MU-MIMO Systems.

For the receiver of multiple-input multiple-output (MIMO) systems, linear detectors are an interesting option due to their good performance and low complexity. Nevertheless, MIMO systems lose diversity in exchange for eliminating interference when linear detectors are used. Aiming to maintain the system diversity while mitigating interference between users, this work proposes a scheduling scheme for the uplink of multiuser MIMO (MU-MIMO) systems that employ A antennas and the zero-forcing (ZF) detector at the receiver in the base station (BS). The channel model includes Rician fading and additive white Gaussian noise (AWGN) in an imperfect channel estimation scenario. The proposed scheme selects U users from a group of Ut users to transmit simultaneously, so that the signal-to-noise ratio (SNR) is maximized. For this, an exact expression to evaluate the SNR of the users is obtained. With this result, the scheduling strategy is proposed. Results show that as Ut increases, the outage probability (OP), and the bit error rate (BER) decrease as the system diversity increases, even when the system is completely loaded, i.e., when U=A. Moreover, it is shown that the scheduling scheme counteracts the imperfect channel estimation effects as Ut increases. Finally, the proposed scheme is tested in presence of an external eavesdropper trying to decode the information sent by the users. The results show that the presented proposal allows for a reduction of the secrecy-outage-probability (SOP) as Ut increases.

9-DOF IMU-Based Attitude and Heading Estimation Using an Extended Kalman Filter with Bias Consideration.

The attitude and heading reference system (AHRS) is an important concept in the area of navigation, image stabilization, and object detection and tracking. Many studies and works have been conducted in this regard to estimate the accurate orientation of rigid bodies. In most research in this area, low-cost MEMS sensors are employed, but since the system's response will diverge over time due to integration drift, it is necessary to apply proper estimation algorithms. A two-step extended Kalman Filter (EKF) algorithm is used in this study to estimate the orientation of an IMU. A 9-DOF device is used for this purpose, including a 6-DOF IMU with a three-axis gyroscope and a three-axis accelerometer, and a three-axis magnetometer. In addition, to have an accurate algorithm, both IMU and magnetometer biases and disturbances are modeled and considered in the real-time filter. After applying the algorithm to the sensor's output, an accurate orientation as well as unbiased angular velocity, linear acceleration, and magnetic field were achieved. In order to demonstrate the reduction of noise power, fast Fourier transform (FFT) diagrams are used. The effect of the initial condition on the response of the system is also investigated.

Early Effects of Extracellular Vesicles Secreted by Adipose Tissue Mesenchymal Cells in Renal Ischemia Followed by Reperfusion: Mechanisms Rely on a Decrease in Mitochondrial Anion Superoxide Production.

Acute kidney injury (AKI) caused by ischemia followed by reperfusion (I/R) is characterized by intense anion superoxide (O2•-) production and oxidative damage. We investigated whether extracellular vesicles secreted by adipose tissue mesenchymal cells (EVs) administered during reperfusion can suppress the exacerbated mitochondrial O2•- formation after I/R. We used Wistar rats subjected to bilateral renal arterial clamping (30 min) followed by 24 h of reperfusion. The animals received EVs (I/R + EVs group) or saline (I/R group) in the kidney subcapsular space. The third group consisted of false-operated rats (SHAM). Mitochondria were isolated from proximal tubule cells and used immediately. Amplex Red™ was used to measure mitochondrial O2•- formation and MitoTracker™ Orange to evaluate inner mitochondrial membrane potential (Δψ). In vitro studies were carried out on human renal proximal tubular cells (HK-2) co-cultured or not with EVs under hypoxic conditions. Administration of EVs restored O2•- formation to SHAM levels in all mitochondrial functional conditions. The gene expression of catalase and superoxide dismutase-1 remained unmodified; transcription of heme oxygenase-1 (HO-1) was upregulated. The co-cultures of HK-2 cells with EVs revealed an intense decrease in apoptosis. We conclude that the mechanisms by which EVs favor long-term recovery of renal structures and functions after I/R rely on a decrease of mitochondrial O2•- formation with the aid of the upregulated antioxidant HO-1/Nuclear factor erythroid 2-related factor 2 system, thus opening new vistas for the treatment of AKI.

Neurogenic bladder - concepts and treatment recommendations.

INTRODUCTION: Bladder and urinary sphincter malfunctioning that results from some change in the central and/or peripheral nervous system is defined as neurogenic bladder. The urinary tract symptoms that can be related to its filling, emptying, or both have a significant impact on the quality of life of individuals. The present review was based on the document prepared for the public health system in Brazil as a treatment guidelines proposal. MATERIAL AND METHODS: Survey questions were structured as per PICO (Population, Intervention, Control, and Outcome). Search strategies were defined and performed in the MEDLINE/Pubmed, Embase, Epistemonikos and Google Scholar databases. The selection of articles followed the evidence hierarchy concept; evidence body was identified, and the quantitative study data were extracted. The quality of evidence and grade of recommendation were qualitatively assessed according to GRADE (Grading of Recommendations, Assessment, Development and Evaluations). RESULTS: A total of 2.707 articles were identified, with 49 of them being selected to compose the basis for this review. Neurogenic bladder treatments were classified according to their focus on filling or emptying symptoms and sub- classified in pharmacological and surgical treatments. CONCLUSION: Treatment guidelines are important tools for the public health system to promote the best practice when treating neurogenic bladder patients.

DNA damage repair as a target in pancreatic cancer: state-of-the-art and future perspectives.

Complex rearrangement patterns and mitotic errors are hallmarks of most pancreatic ductal adenocarcinomas (PDAC), a disease with dismal prognosis despite some therapeutic advances in recent years. DNA double-strand breaks (DSB) bear the greatest risk of provoking genomic instability, and DNA damage repair (DDR) pathways are crucial in preserving genomic integrity following a plethora of damage types. Two major repair pathways dominate DSB repair for safeguarding the genome integrity: non-homologous end joining and homologous recombination (HR). Defective HR, but also alterations in other DDR pathways, such as BRCA1, BRCA2, ATM and PALB2, occur frequently in both inherited and sporadic PDAC. Personalised treatment of pancreatic cancer is still in its infancy and predictive biomarkers are lacking. DDR deficiency might render a PDAC vulnerable to a potential new therapeutic intervention that increases the DNA damage load beyond a tolerable threshold, as for example, induced by poly (ADP-ribose) polymerase inhibitors. The Pancreas Cancer Olaparib Ongoing (POLO) trial, in which olaparib as a maintenance treatment improved progression-free survival compared with placebo after platinum-based induction chemotherapy in patients with PDAC and germline BRCA1/2 mutations, raised great hopes of a substantially improved outcome for this patient subgroup. This review summarises the relationship between DDR and PDAC, the prevalence and characteristics of DNA repair mutations and options for the clinical management of patients with PDAC and DNA repair deficiency.

Nanometer scale insight on the analysis of limpets mineralized teeth: Special focus on the silica-containing regions.

We report the electron microscopy-based analysis of the major lateral tooth of the limpet Colisella subrugosa during early and intermediate stages of development. We aimed to analyze the structural relationship among the needle-like crystals of the iron oxide goethite, the amorphous silica phase that forms the tooth base and occupy inter-crystalline spaces in the cusp, and the chitin fibers of the matrix. Goethite crystals followed the three dimensional organization pattern of the chitin fibers in the cusp. In the tooth base, spherical individual silica granules were found in regions where the chitin fibers cross. The spherical granules near the interface between the tooth base and the cusp (junction zone) formed an almost continuous medium that could easily be ultrathin-sectioned for further analysis. By contrast, the nearby silica-rich region localized on the other side of the junction zone contained needle-like goethite crystals immersed in the matrix and presented a conchoidal fracture. The chitin fibers from the silica granules of the tooth base were dotted or undulating in projection with a periodicity of about 6 nm when observed by high magnification transmission electron microscopy. Very thin goethite crystals were present in the base of the cusp near the junction zone surrounded by silica. On several occasions, crystals presented internal thin straight white lines parallel to the major axis, indicating a possible growth around fibers. We propose that silica and iron oxide phases mineralization may occur simultaneously at least for some period and that silica moderates the dimensions of the iron oxide crystals.

Modeling Early Warning Systems: Construction and Validation of a Discrete Event Simulation Model for Heart Failure.

OBJECTIVES: Developing and validating a discrete event simulation model that is able to model patients with heart failure managed with usual care or an early warning system (with or without a diagnostic algorithm) and to account for the impact of individual patient characteristics in their health outcomes. METHODS: The model was developed using patient-level data from the Trans-European Network - Home-Care Management System study. It was coded using RStudio Version 1.3.1093 (version 3.6.2.) and validated along the lines of the Assessment of the Validation Status of Health-Economic decision models tool. The model includes 20 patient and disease characteristics and generates 8 different outcomes. Model outcomes were generated for the base-case analysis and used in the model validation. RESULTS: Patients managed with the early warning system, compared with usual care, experienced an average increase of 2.99 outpatient visits and a decrease of 0.02 hospitalizations per year, with a gain of 0.81 life years (0.45 quality-adjusted life years) and increased average total costs of €11 249. Adding a diagnostic algorithm to the early warning system resulted in a 0.92 life year gain (0.57 quality-adjusted life years) and increased average costs of €9680. These patients experienced a decrease of 0.02 outpatient visits and 0.65 hospitalizations per year, while they avoided being hospitalized 0.93 times. The model showed robustness and validity of generated outcomes when comparing them with other models addressing the same problem and with external data. CONCLUSIONS: This study developed and validated a unique patient-level simulation model that can be used for simulating a wide range of outcomes for different patient subgroups and treatment scenarios. It provides useful information for guiding research and for developing new treatment options by showing the hypothetical impact of these interventions on a large number of important heart failure outcomes.

Long-term outcome of cementless total hip arthroplasty with threaded Tropic® acetabular cup and Corail® femoral stem.

This study investigates the clinical and radiological results of a tapered femoral stem (Corail®) and uncemented threaded acetabular cups (Tropic®) and in addition an analysis of the complications and retrieved implants was conducted. Between January 1990 and September 1998, 301 total hips arthroplasties in 268 patients were implanted. 78 patients (87 hips) had died and 9 patients (12 hips) had been lost to follow-up, leaving at the time of the latest follow-up 180 patients (202 hips). The mean age at surgery was 56,1 (27-75) years. Of the 154 unrevised hips, the median Harris and Merle d'Aubigne and Postel hip scores were 83,3 points and 15,3 points respectively at the latest follow-up. The median follow-up time was 16.9 years (10,4-25). No femoral component was revised for aseptic loosening ; osteolysis was observed in the 9,5% of the implants (13 stems). 48 hips (23%) were revised and 27 cups (56,2%) needed revision surgery because of massive polyethylene wear. Pelvic osteolysis was found out in 80 cups (58,8%). 87 hips (63,9%) showed signs of a progressive wear of the liner, more than 2mm in 48 hips. Kaplan-Meier survivorship analysis at 15 years follow-up was 81.2% with revision for any reason (85.8% for mechanical or radiographic loosening). High rates of polyethylene wear and the high prevalence of pelvic osteolysis are serious matters in these types of implants with high rates of revision at 15 years follow-up so we decided to abandon the concept of a threaded cup design in favor of a press-fit acetabular cup.