Learning to deep learning: statistics and a paradigm test in selecting a UNet architecture to enhance MRI.

OBJECTIVE: This study aims to assess the statistical significance of training parameters in 240 dense UNets (DUNets) used for enhancing low Signal-to-Noise Ratio (SNR) and undersampled MRI in various acquisition protocols. The objective is to determine the validity of differences between different DUNet configurations and their impact on image quality metrics. MATERIALS AND METHODS: To achieve this, we trained all DUNets using the same learning rate and number of epochs, with variations in 5 acquisition protocols, 24 loss function weightings, and 2 ground truths. We calculated evaluation metrics for two metric regions of interest (ROI). We employed both Analysis of Variance (ANOVA) and Mixed Effects Model (MEM) to assess the statistical significance of the independent parameters, aiming to compare their efficacy in revealing differences and interactions among fixed parameters. RESULTS: ANOVA analysis showed that, except for the acquisition protocol, fixed variables were statistically insignificant. In contrast, MEM analysis revealed that all fixed parameters and their interactions held statistical significance. This emphasizes the need for advanced statistical analysis in comparative studies, where MEM can uncover finer distinctions often overlooked by ANOVA. DISCUSSION: These findings highlight the importance of utilizing appropriate statistical analysis when comparing different deep learning models. Additionally, the surprising effectiveness of the UNet architecture in enhancing various acquisition protocols underscores the potential for developing improved methods for characterizing and training deep learning models. This study serves as a stepping stone toward enhancing the transparency and comparability of deep learning techniques for medical imaging applications.

Safety aspects of the PiCCO thermodilution-cardiac output catheter during magnetic resonance imaging at 3 Tesla.

Thermodilution cardiac output monitoring, using a thermistor-tipped intravascular catheter, is used in critically ill patients to guide hemodynamic therapy. Often, these patients also need magnetic resonance imaging (MRI) for diagnostic or prognostic reasons. As thermodilution catheters contain metal, they are considered MRI-unsafe and advised to be removed prior to investigation. However, removal and replacement of the catheter carries risks of bleeding, perforation and infection. This research is an in vitro safety assessment of the PiCCO™ thermodilution catheter during 3 T Magnetic Resonance Imaging (3T-MRI).  In a 3T-MRI environment, three different PiCCO™ catheter sizes were investigated in an agarose-gel, tissue mimicking phantom. Two temperature probes measured radiofrequency-induced heating; one at the catheter tip and one at a reference point. Magnetically induced catheter dislocation was assessed by visual observation as well as by analysis of the tomographic images. For all tested catheters, the highest measured temperature increase was 0.2 °C at the center of the bore and 0.3 °C under "worst-case" setting for the tested MRI pulse sequences. No magnetically induced catheter displacements were observed. Under the tested circumstances, no heating or dislocation of the PiCCO™ catheter was observed in a tissue mimicking phantom during 3T-MRI. Leaving the catheter in the critically ill patient during MRI investigation might pose a lower risk of complications than catheter removal and replacement.

Evaluation of how users interface with holographic augmented reality surgical scenes: Interactive planning MR-Guided prostate biopsies.

BACKGROUND: User interfaces play a vital role in the planning and execution of an interventional procedure. The objective of this study is to investigate the effect of using different user interfaces for planning transrectal robot-assisted MR-guided prostate biopsy (MRgPBx) in an augmented reality (AR) environment. METHOD: End-user studies were conducted by simulating an MRgPBx system with end- and side-firing modes. The information from the system to the operator was rendered on HoloLens as an output interface. Joystick, mouse/keyboard, and holographic menus were used as input interfaces to the system. RESULTS: The studies indicated that using a joystick improved the interactive capacity and enabled operator to plan MRgPBx in less time. It efficiently captures the operator's commands to manipulate the augmented environment representing the state of MRgPBx system. CONCLUSIONS: The study demonstrates an alternative to conventional input interfaces to interact and manipulate an AR environment within the context of MRgPBx planning.

A Holographic Augmented Reality Interface for Visualizing of MRI Data and Planning of Neurosurgical Procedures.

The recent introduction of wireless head-mounted displays (HMD) promises to enhance 3D image visualization by immersing the user into 3D morphology. This work introduces a prototype holographic augmented reality (HAR) interface for the 3D visualization of magnetic resonance imaging (MRI) data for the purpose of planning neurosurgical procedures. The computational platform generates a HAR scene that fuses pre-operative MRI sets, segmented anatomical structures, and a tubular tool for planning an access path to the targeted pathology. The operator can manipulate the presented images and segmented structures and perform path-planning using voice and gestures. On-the-fly, the software uses defined forbidden-regions to prevent the operator from harming vital structures. In silico studies using the platform with a HoloLens HMD assessed its functionality and the computational load and memory for different tasks. A preliminary qualitative evaluation revealed that holographic visualization of high-resolution 3D MRI data offers an intuitive and interactive perspective of the complex brain vasculature and anatomical structures. This initial work suggests that immersive experiences may be an unparalleled tool for planning neurosurgical procedures.

End-user evaluation of software-generated intervention planning environment for transrectal magnetic resonance-guided prostate biopsies.

BACKGROUND: This study presents user evaluation studies to assess the effect of information rendered by an interventional planning software on the operator's ability to plan transrectal magnetic resonance (MR)-guided prostate biopsies using actuated robotic manipulators. METHODS: An intervention planning software was developed based on the clinical workflow followed for MR-guided transrectal prostate biopsies. The software was designed to interface with a generic virtual manipulator and simulate an intervention environment using 2D and 3D scenes. User studies were conducted with urologists using the developed software to plan virtual biopsies. RESULTS: User studies demonstrated that urologists with prior experience in using 3D software completed the planning less time. 3D scenes were required to control all degrees-of-freedom of the manipulator, while 2D scenes were sufficient for planar motion of the manipulator. CONCLUSIONS: The study provides insights on using 2D versus 3D environment from a urologist's perspective for different operational modes of MR-guided prostate biopsy systems.

A modular and scalable computational framework for interactive immersion into imaging data with a holographic augmented reality interface.

BACKGROUND AND OBJECTIVE: Modern imaging scanners produce an ever-growing body of 3D/4D multimodal data requiring image analytics and visualization of fused images, segmentations, and information. For the latter, augmented reality (AR) with head-mounted displays (HMDs) has shown potential. This work describes a framework (FI3D) for interactive immersion with data, integration of image processing and analytics, and rendering and fusion with an AR interface. METHODS: The FI3D was designed and endowed with modules to communicate with peripherals, including imaging scanners and HMDs, and to provide computational power for data acquisition and processing. The core of FI3D is deployed to a dedicated computational unit that performs the computationally demanding processes in real-time, and the HMD is used as a display output peripheral and an input peripheral through gestures and voice commands. FI3D offers user-made processing and analysis dedicated modules. Users can customize and optimize these for a particular workflow while incorporating current or future libraries. RESULTS: The FI3D framework was used to develop a workflow for processing, rendering, and visualization of CINE MRI cardiac sets. In this version, the data were loaded from a remote database, and the endocardium and epicardium of the left ventricle (LV) were segmented using a machine learning model and transmitted to a HoloLens HMD to be visualized in 4D. Performance results show that the system is capable of maintaining an image stream of one image per second with a resolution of 512 × 512. Also, it can modify visual properties of the holograms at 1 update per 16 milliseconds (62.5 Hz) while providing enough resources for the segmentation and surface reconstruction tasks without hindering the HMD. CONCLUSIONS: We provide a system design and framework to be used as a foundation for medical applications that benefit from AR visualization, removing several technical challenges from the developmental pipeline.

Left Ventricular Geometrical Changes in Severely Obese Adolescents: Prevalence, Determinants, and Clinical Implications.

Left ventricular hypertrophy (LVH) is independently associated with a higher risk of cardiovascular morbidity and mortality in adults. Adiposity is a risk factor for LVH, independent of blood pressure. Potential causes of this nonhemodynamic pathogenesis identified in adults include adverse body fat distribution, insulin resistance, dyslipidemia, and obstructive sleep apnea syndrome (OSA). In severely obese adolescents, the determinants of obesity-induced changes in left ventricular structure are poorly characterized. Cardiac ultrasonographic, demographic, anthropometric, and comorbidity-related data were prospectively collected in adolescents with severe obesity refractory to conservative treatment who presented for surgical therapy. Differences between adolescents with LVH and without LVH were evaluated using independent samples t, chi-square, or Fisher's exact test. Multivariable linear regression analysis was performed to evaluate associations with left ventricular structural changes, corrected for body mass index (BMI) z score. Forty-three patients entered analysis, of whom 24 (55.8%) showed LVH. The most common geometrical change was eccentric LVH (eLVH), occurring in 21 subjects (48.8%). Demographic and anthropometric variables did not differ between patients with and without LVH. Independent of BMI z score, left ventricular mass index was significantly associated with apnea-hypopnea index (AHI) (regression parameter B = 0.8; 95% CI 0.3 to 1.2). Interventricular septum thickness (IVST) was significantly associated with HOMA-IR values (B = 0.1; 95% CI 0.04 to 0.2), HDL-cholesterol (B = - 1.2; 95% CI - 2.2 to 0.1), and triglyceride levels (B = 0.5; 95% CI 0.001 to 0.9). LVH, especially eLVH, is highly prevalent amongst severely obese adolescents. Adverse changes in cardiac structure, increased IVST in particular, are independently associated with several nonhemodynamic comorbidities that are common in this population, namely OSA, insulin resistance, and dyslipidemia.

Obstructive sleep apnea in obese adolescents referred for bariatric surgery: association with metabolic and cardiovascular variables.

BACKGROUND: obstructive sleep apnea syndrome (OSA) is a well-described disease entity in adults, with a higher prevalence in severely obese individuals, while at the same time associated with several comorbidities independently of BMI. Literature regarding OSA in severely obese adolescents is qualitatively and quantitatively limited, possibly resulting in suboptimal diagnosis and treatment. METHODS: polysomnographic, demographic, anthropometric, and comorbidity-related data were prospectively collected in 56 adolescents with morbid obesity refractory to conservative treatment who presented for surgical therapy. Differences between adolescents with no/mild (apnea-hypopnea index (AHI) 0-4.9) and moderate/severe OSA (AHI ≥ 5.0) were evaluated using independent-samples t, chi-square or Fisher's exact tests. Multivariable linear regression analysis was performed to evaluate the association of several variables with AHI, corrected for BMI z-score. RESULTS: of the 53 included subjects, 48 (90.6%) showed some degree of sleep disordered breathing and 20 (37.7%) had moderate/severe OSA. Patients with moderate/severe OSA had on average a higher neck circumference (42.4 versus 40.1 cm, p = 0.008), higher BMI z-score (3.7 versus 3.4, p = 0.003), higher plasma triglyceride level (2.2 versus 1.5 mmol/L, p = 0.012), and lower IGF (29.6 versus 40.2 mmol/L, p = 0.010) than those with no/mild OSA. BMI z-score and plasma triglyceride levels were independently related to AHI. CONCLUSIONS: OSA is highly prevalent amongst morbidly obese adolescents and is strongly associated with BMI z-score. Elevated plasma triglyceride levels are associated with AHI, independent of BMI z-score.

Sternocostal instability after Ravitch repair in adolescents; 3 case-reports and a review of surgical techniques in the literature.

Ravitch repair is a common surgical procedure to correct chest wall deformities. In this procedure, a subperichondreal cartilage resection of the deformed parasternal cartilage, and if necessary a repositioning of the sternum, is performed. Insufficient regeneration of the resected cartilage may result in sternocostal instability or even floating sternum. This rare complication presents with symptoms of pain and exercise intolerance. METHODS: We describe sternocostal instability in 3 adolescent patients after the Ravitch procedure for pectus carinatum and reviewed the literature on this topic. RESULTS: Our patients suffered different degrees of instability. In all cases, we eventually achieved a satisfactory outcome. There is little literature on sternocostal instability. It is a rare complication, mainly occurring after reoperation by damaging the perichondrium. CONCLUSIONS: Malunion of costal cartilage is a rare complication of open pectus repair. To achieve the best regeneration and stability of the sternum, less extended resection of cartilage should be performed and the number of cartilages resected should be limited. The perichondrium must be kept intact. Autologous grafts, growth-enhancing materials, and metal or bioabsorbable struts may contribute to stabilization and regeneration of the cartilage.

Volumetry of Mesiotemporal Structures Reflects Serostatus in Patients with Limbic Encephalitis.

BACKGROUND AND PURPOSE: Limbic encephalitis is an autoimmune disease. A variety of autoantibodies have been associated with different subtypes of limbic encephalitis, whereas its MR imaging signature is uniformly characterized by mesiotemporal abnormalities across subtypes. Here, we hypothesized that patients with limbic encephalitis would show subtype-specific mesiotemporal structural correlates, which could be classified by supervised machine learning on an individual level. MATERIALS AND METHODS: T1WI MPRAGE scans from 46 patients with antibodies against glutamic acid decarboxylase and 34 patients with antibodies against the voltage-gated potassium channel complex (including 10 patients with leucine-rich glioma-inactivated 1 autoantibodies) and 48 healthy controls were retrospectively ascertained. Parcellation of the amygdala, hippocampus, and hippocampal subfields was performed using FreeSurfer. Volumes were extracted and compared between groups using unpaired, 2-tailed t tests. The volumes of hippocampal subfields were analyzed using a multivariate linear model and a binary decision tree classifier. RESULTS: Temporomesial volume alterations were most pronounced in an early stage and in the affected hemispheric side of patients. Statistical analysis revealed antibody-specific hippocampal fingerprints with a higher volume of CA1 in patients with glutamic acid decarboxylase-associated limbic encephalitis (P = .02), compared with controls, whereas CA1 did not differ from that in controls in patients with voltage-gated potassium channel complex autoantibodies. The classifier could successfully distinguish between patients with autoantibodies against leucine-rich glioma-inactivated 1 and glutamic acid decarboxylase with a specificity of 87% and a sensitivity of 80%. CONCLUSIONS: Our results suggest stage-, side- and antibody-specific structural correlates of limbic encephalitis; thus, they create a perspective toward an MR imaging-based diagnosis.

Diagnostic accuracy of flat-panel computed tomography in assessing cerebral perfusion in comparison with perfusion computed tomography and perfusion magnetic resonance: a systematic review.

PURPOSE: Flat-panel computed tomography (FP-CT) is increasingly available in angiographic rooms and hybrid OR's. Considering its easy access, cerebral imaging using FP-CT is an appealing modality for intra-procedural applications. The purpose of this systematic review is to assess the diagnostic accuracy of FP-CT compared with perfusion computed tomography (CTP) and perfusion magnetic resonance (MRP) in cerebral perfusion imaging. METHODS: We performed a systematic literature search in the Cochrane Library, MEDLINE, Embase, and Web of Science up to June 2019 for studies directly comparing FP-CT with either CTP or MRP in vivo. Methodological quality was assessed using the QUADAS-2 tool. Data on diagnostic accuracy was extracted and pooled if possible. RESULTS: We found 11 studies comparing FP-CT with CTP and 5 studies comparing FP-CT with MRP. Most articles were pilot or feasibility studies, focusing on scanning and contrast protocols. All patients studied showed signs of cerebrovascular disease. Half of the studies were animal trials. Quality assessment showed unclear to high risks of bias and low concerns regarding applicability. Five studies reported on diagnostic accuracy; FP-CT shows good sensitivity (range 0.84-1.00) and moderate specificity (range 0.63-0.88) in detecting cerebral blood volume (CBV) lesions. CONCLUSIONS: Even though FP-CT provides similar CBV values and reconstructed blood volume maps as CTP in cerebrovascular disease, additional studies are required in order to reliably compare its diagnostic accuracy with cerebral perfusion imaging.

Impact of Cold Ischemia Time on Outcomes of Deceased Donor Kidney Transplantation: An Analysis of a National Registry.

BACKGROUND: Cold ischemia time (CIT) is known to impact kidney graft survival rates. We compare the impact of CIT on graft failure and mortality in circulatory death versus brain death donor kidneys and how it relates to donor age. METHODS: We used the prospective Dutch Organ Transplantation Registry to include 2153 adult recipients of brain death (n = 1266) and circulatory death (n = 887) donor kidneys after static cold storage from transplants performed between 2005 and 2012. CIT was modeled nonlinearly with splines. Associations and interactions between CIT, donor type, donor age, 5-year (death-censored) graft survival, and mortality were evaluated. RESULTS: The median CIT was 16.2 hours (interquartile range 12.8-20), ranging from 3.4 to 44.7 hours for brain death and 4.7 to 46.6 hours for circulatory death donor kidneys. At >12 hours of CIT, we observed an increased risk of graft failure in kidneys donated after circulatory death versus after brain death. This risk rose significantly at >22 hours of CIT (hazard ratio 1.45; 95% confidence interval, 1.01-2.49; P = 0.043). Kidneys that came from 60-year-old circulatory death donors demonstrated elevated hazard risk at 19 hours of CIT, a shorter timeline than that for kidneys that came from brain death donors of the same age (hazard ratio 1.33; 95% confidence interval, 1.00-1.78; P = 0.045). The additional harmful effects of increased CIT in kidneys from circulatory-death donors were also found for death-censored graft failure but did not affect mortality rates in any significant way. CONCLUSIONS: The findings support the hypothesis that prolonged cold ischemia is more harmful for circulatory death donor kidneys that have already been subjected to a permissible period of warm ischemia. Efforts should be made to reduce CIT, especially for older circulatory death donor kidneys.

Early cost-utility estimation of the surgical correction of pectus excavatum with the Nuss bar.

OBJECTIVES: The surgical correction of pectus excavatum (PE) with a Nuss bar provides satisfactory outcomes, but its cost-effectiveness is yet unproven. We prospectively analysed early outcomes and costs for Nuss bar placement. METHODS: Fifty-four patients aged 16 years or older (6 females and 48 males; mean age, 17.9 years; range 16.0-29.4 years) with a PE filled out a Short Form-36 Health Survey (SF-6D) preoperatively and 1 year after a Nuss procedure. Costs included professional fees and fees for the operating room, materials and hospital care. Changes in the responses to the SF-36 or its domains were compared using the Wilcoxon signed rank test and the utility test results were calculated preoperatively and postoperatively from the SF-6D. The quality-adjusted life years (QALYs) were calculated from the results of these tests. RESULTS: Significant improvements in physical functioning, social functioning, mental health and health transition (all P < 0.05) were noted. The other SF-36 subgroups showed improvement; however, the improvement was not significant. The SF-6D utility showed improvement from 0.76 preoperatively to 0.79 at the 1-year follow-up (P = 0.096). The mean direct costs were €8805. The 1-year discounted QALY gain was 0.03. The estimated cost-utility ratio was €293 500 per QALY gained. CONCLUSIONS: Despite a significant improvement in many domains of the SF-36, the results of the SF-6D cost-utility analysis showed only a small improvement in cost-effectiveness (> €80 000/QALY) for patients with PE 1 year after Nuss bar placement. Based on this discrepancy, general health outcome measurements as the basis for cost-utility analysis in patients with PE may not be the best way forward.

Clinical recovery in children with uncomplicated appendicitis undergoing non-operative treatment: secondary analysis of a prospective cohort study.

Non-operative treatment of uncomplicated appendicitis in children is gaining ground. Pending definitive evidence regarding its effectiveness, there is a call to evaluate clinical recovery after non-operative treatment. In this study, we analyzed data collected during initial admission of a multicenter prospective cohort in which children, 7-17 year, were treated non-operatively for uncomplicated appendicitis. During admission clinical parameters (pain and gastro-intestinal symptoms), inflammation parameters and sequential abdominal ultrasound were recorded. In total, 45 children were included, 42(93%) were discharged without the need for appendectomy; median [IQR] pain scores on admission were 5 [4-7], decreasing to 2 [0-3] after 1 day of treatment. Initially, 28/42 (67%) reported nausea and 19/42 (45%) vomiting; after 1 day, this was 3/42 (7%) and 1/42 (2%), respectively. White blood cell count declined from a median [IQR] of 12.9 [10.7-16.7] 10E9/L on admission to 7.0 [5.8-9.9] 10E9/L on day 1. Median [IQR] C-reactive protein levels increased from 27.5 [9-69] mg/L on admission to 48 [22-80] mg/L on day 1, declining to 21.5 [11-42] mg/L on day 2. Follow-up ultrasound showed no signs of complicated appendicitis in any of the patients.Conclusion: Clinical symptoms resolved in most children after 1 day of non-operative treatment. This suggests that non-operative treatment is a viable alternative to appendectomy regarding clinical recovery.Trail registration: NCT01356641 What is Known: • Non-operative treatment of uncomplicated appendicitis in children is safe and its use around the world is gaining ground, however high quality evidence from adequately designed randomized trials is still lacking. • Concerns have been raised regarding the potentially prolonged clinical recovery associated with non-operative treatment. What is New: • Most clinical symptoms resolve after 1 day of non-operative treatment in the majority of children.

Medical and social costs after using financial incentives to improve medication adherence: results of a 1 year randomised controlled trial.

OBJECTIVE: Offering a financial incentive ('Money for Medication') is effective in improving adherence to treatment with depot antipsychotic medications. We investigated the cost-effectiveness in terms of medical costs and judicial expenses of using financial incentives to improve adherence. The effects of financial incentives on depot medication adherence were evaluated in a randomised controlled trial. Patients in the intervention group received €30 a month over 12 months if antipsychotic depot medication was accepted. The control group received mental health care as usual. For 133 patients outcomes were calculated based on self-reported service use and delinquent behaviour and expressed as standard unit costs to value resource use. RESULTS: The financial incentive resulted in higher average costs related to mental health care (€449.6 versus €355.7). and lower medical costs related to other healthcare services (€52.0 versus €78.4). Relevant differences in social costs related to delinquent behaviour were not found. Although wide confidence intervals indicate uncertainty, incremental cost-effectiveness ratio's (ICER) indicate that it costs €2080 for achieving a 20% increase in adherence or €3332 for achieving over 80% adherence. In sum, offering money as financial incentive for increasing compliance did not lead to an overall cost reduction as compared to care as usual. Trial registration NTR2350, 01 June 2010.

The effect of financial incentives on patients' motivation for treatment: results of "Money for Medication," a randomised controlled trial.

BACKGROUND: Offering financial incentives is an effective intervention for improving adherence in patients taking antipsychotic depot medication. We assessed whether patients' motivation for treatment might be reduced after receiving financial rewards. METHODS: This study was part of Money for Medication, a multicentre, open-label, randomised controlled trial, which demonstrated the positive effects of financial incentives on antipsychotic depot compliance. Three mental healthcare institutions in Dutch secondary psychiatric care services participated. Eligible patients were aged 18-65 years, had been diagnosed with schizophrenia or another psychotic disorder, had been prescribed antipsychotic depot medication or had an indication to start using depot medication, and were participating in outpatient treatment. For 12 months, patients were randomly assigned either to treatment as usual (control group) or to treatment as usual plus a financial reward for each depot of medication received (€30 per month if fully compliant; intervention group). They were followed up for 6 months, during which time no monetary rewards were offered for taking antipsychotic medication. To assess treatment motivation after 0, 12 and 18 months, interviews were conducted using a supplement to the Health of the Nation Outcome Scales (HoNOS) and the Treatment Entry Questionnaire (TEQ). RESULTS: Patients were randomly assigned to the intervention (n = 84) or the control group (n = 85). After 12 months, HoNOS motivation scores were available for 131 patients (78%). Ninety-one percent of the patients had no or mild motivational problems for overall treatment; over time, there were no significant differences between the intervention and control groups. TEQ data was available for a subgroup of patients (n = 61), and showed no significant differences over time between the intervention and control groups for external motivation (ß = 0.37 95% CI: -2.49 - 3.23, p = 0.799); introjected motivation (ß = - 2.39 95% CI: -6.22 - 1.44, p = 0.222); and identified motivation (ß = - 0.91 95% CI: -4.42 - 2.61, p = 0.613). After the 6-month follow-up period, results for the HoNOS and TEQ scores remained comparable. CONCLUSIONS: Offering financial incentives for taking antipsychotic depot medication does not reduce patients' motivation for treatment. TRIAL REGISTRATION: Netherlands Trial registration, number NTR2350 .

[Redo urethroplasty with buccal mucosa]. / Redo-Harnröhrenplastik mit Mundschleimhaut.

Urethral strictures can occur on the basis of trauma, infections, iatrogenic-induced or idiopathic and have a great influence on the patient's quality of life. The current prevalence rate of male urethral strictures is 0.6% in industrialized western countries. The favored form of treatment has experienced a transition from less invasive interventions, such as urethrotomy or urethral dilatation, to more complex open surgical reconstruction. Excision and primary end-to-end anastomosis and buccal mucosa graft urethroplasty are the most frequently applied interventions with success rates of more than 80%. Risk factors for stricture recurrence after urethroplasty are penile stricture location, the length of the stricture (>4 cm) and prior repeated endoscopic therapy attempts. Radiation-induced urethral strictures also have a worse outcome. There are various therapy options in the case of stricture recurrence after a failed urethroplasty. In the case of short stricture recurrences, direct vision urethrotomy shows success rates of approximately 60%. In cases of longer or more complex stricture recurrences, redo urethroplasty should be the therapy of choice. Success rates are higher than after urethrotomy and almost comparable to those of primary urethroplasty. Patient satisfaction after redo urethroplasty is high. Primary buccal mucosa grafting involves a certain rate of oral morbidity. In cases of a redo urethroplasty with repeated buccal mucosa grafting, oral complications are only slightly higher.

Ethical acceptability of offering financial incentives for taking antipsychotic depot medication: patients' and clinicians' perspectives after a 12-month randomized controlled trial.

BACKGROUND: A randomized controlled trial 'Money for Medication'(M4M) was conducted in which patients were offered financial incentives for taking antipsychotic depot medication. This study assessed the attitudes and ethical considerations of patients and clinicians who participated in this trial. METHODS: Three mental healthcare institutions in secondary psychiatric care in the Netherlands participated in this study. Patients (n = 169), 18-65 years, diagnosed with schizophrenia, schizoaffective disorder or another psychotic disorder who had been prescribed antipsychotic depot medication, were randomly assigned to receive 12 months of either treatment as usual plus a financial reward for each depot of medication received (intervention group) or treatment as usual alone (control group). Structured questionnaires were administered after the 12-month intervention period. Data were available for 133 patients (69 control and 64 intervention) and for 97 clinicians. RESULTS: Patients (88%) and clinicians (81%) indicated that financial incentives were a good approach to improve medication adherence. Ethical concerns were categorized according to the four-principles approach (autonomy, beneficence, non-maleficence, and justice). Patients and clinicians alike mentioned various advantages of M4M in clinical practice, such as increased medication adherence and improved illness insight; but also disadvantages such as reduced intrinsic motivation, loss of autonomy and feelings of dependence. CONCLUSIONS: Overall, patients evaluated financial incentives as an effective method of improving medication adherence and were willing to accept this reward during clinical treatment. Clinicians were also positive about the use of this intervention in daily practice. Ethical concerns are discussed in terms of patient autonomy, beneficence, non-maleficence and justice. We conclude that this intervention is ethically acceptable under certain conditions, and that further research is necessary to clarify issues of benefit, motivation and the preferred size and duration of the incentive. TRIAL REGISTRATION: Nederlands Trial Register, number NTR2350 .

The pathogenic LRRK2 R1441C mutation induces specific deficits modeling the prodromal phase of Parkinson's disease in the mouse.

The aim of the present study was to further explore the in vivo function of the Leucine-rich repeat kinase 2 (LRRK2)-gene, which is mutated in certain familial forms of Parkinson's disease (PD). We generated a mouse model harboring the disease-associated point mutation R1441C in the GTPase domain of the endogenous murine LRRK2 gene (LRRK2 R1441C line) and performed a comprehensive analysis of these animals throughout lifespan in comparison with an existing knockdown line of LRRK2 (LRRK2 knockdown line). Animals of both lines do not exhibit severe motor dysfunction or pathological signs of neurodegeneration neither at young nor old age. However, at old age the homozygous LRRK2 R1441C animals exhibit clear phenotypes related to the prodromal phase of PD such as impairments in fine motor tasks, gait, and olfaction. These phenotypes are only marginally observable in the LRRK2 knockdown animals, possibly due to activation of compensatory mechanisms as suggested by in vitro studies of synaptic transmission. Thus, at the organismal level the LRRK2 R1441C mutation does not emerge as a loss of function of the protein, but induces mutation specific deficits. Furthermore, judged by the phenotypes presented, the LRRK2-R1441C knock-in line is a valid preclinical model for the prodromal phase of PD.

The Dynamic Compression Brace for Pectus Carinatum: Intermediate Results in 286 Patients.

BACKGROUND: Dynamic brace compression is a novel treatment for patients with pectus carinatum. The dynamic compression system contains a device to measure the flexibility of the thoracic wall and regulate the pressure of the brace. METHODS: Patients referred to our pediatric surgical center were screened for treatment with the dynamic compression brace. Patients with a pressure of initial correction (PIC) of 10.0 pounds per square inch or less were offered treatment with the brace. Patients with a PIC above 10.0 pounds per square inch were offered surgical correction. Between March 2013 and April 2016, 286 patients were treated with the brace; 260 were male (91%) and 26 were female (9%). Their mean age was 14 years (range, 4 to 21 years). RESULTS: Seventy-eight patients completed brace treatment; the mean treatment time was 14 months. Twenty-seven patients abandoned treatment because of lack of motivation, loss to follow-up, persistent protrusion of the sternal bone or flaring that required surgical correction, failure of treatment because of a bifid rib, fear of locking the brace, and delayed correction. One hundred eighty-one patients are still wearing the brace, either in the active or in the retainer phase. Patients with a high PIC also showed improvement when they were compliant. Adverse events were minor and included skin lesions (n = 4, 1%) and vasovagal reactions at the start of therapy (n = 3, 1%). CONCLUSIONS: These data show that brace therapy can be considered a valuable treatment option to correct pectus carinatum in patients with a flexible thorax.