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The CARLO (cold ablation robot-guided laser osteotome) is a compact device with integrated multiple sensory, steering and safety checking elements. A multi-center study was performed to evaluate the CARLO device for the linear part of midface osteotomy in 28 patients. Feasibility, success rate, safety, performance and experience of the surgeons were assessed and evaluated. All 28 procedures were completed with CARLO without falling back to the conventional methods, giving a technical success rate of 100%. For 27 (96%) cases, procedural success was achieved with cutting lines deviation less than 2 mm. For 25 procedures, the CARLO-cutting was conducted smoothly. In the other 3 cases, some minor difficulties related to the reference markers were reported. For 18 procedures, no change for the cutting path was necessary. For the other 10 cases, cut path was adapted. Intraoperative re-planning was possible, easy and quick without significant delay of the procedures. No CARLO-related adverse events were recorded. Especially, there was no unexpected and unusual bleeding during the CARLO-conducted osteotomy. The time needed for the registration ranged from 1 to 12 min (median = 4). The CARLO-cutting lasted for 5 to 21 min (median = 7). The present study demonstrated feasibility, simplicity, safety, reliability and accuracy of CARLO for the linear part of midface osteotomy., (© 2024. The Author(s).)

Kitaev chains in quantum dot-superconductor arrays are a promising platform for the realization of topological superconductivity. As recently demonstrated, even a two-site chain can host Majorana zero modes known as "poor man's Majorana". Harnessing the potential of these states for quantum information processing, however, requires increasing their robustness to external perturbations. Here, we form a two-site Kitaev chain using Yu-Shiba-Rusinov states in proximitized quantum dots. By deterministically tuning the hybridization between the quantum dots and the superconductor, we observe poor man's Majorana states with a gap larger than 70 μeV. The sensitivity to charge fluctuations is also greatly reduced compared to Kitaev chains made with non-proximitized dots. The systematic control and improved energy scales of poor man's Majorana states realized with Yu-Shiba-Rusinov states will benefit the realization of longer Kitaev chains, parity qubits, and the demonstration of non-Abelian physics., (© 2024. The Author(s).)

Objectives: The aim of this study was to identify cone-beam computed tomography (CBCT) protocols that offer an optimal balance between effective dose (ED) and 3D model for orthognathic virtual surgery planning, using CT as a reference, and to assess whether such protocols can be defined based on technical image quality metrics., Methods: Eleven CBCT (VISO G7, Planmeca Oy, Helsinki, Finland) scan protocols were selected out of 32 candidate protocols, based on ED and technical image quality measurements. Next, an anthropomorphic RANDO SK150 phantom was scanned using these 11 CBCT protocols and 2 CT scanners for bone quantity assessments. The resulting DICOM (Digital Imaging and Communications in Medicine) files were converted into Standard Tessellation Language (STL) models that were used for bone volume and area measurements in the predefined orbital region to assess the validity of each CBCT protocol for virtual surgical planning., Results: The highest CBCT bone volume and area of the STL models were obtained using normal dose protocol (F2) and ultra-low dose protocol (J13), which resulted in 48% and 96% of the mean STL bone volume and 48% and 95% of the bone area measured on CT scanners, respectively., Conclusions: The normal dose CBCT protocol "F2" offered optimal bone area and volume balance for STL. The optimal CBCT protocol can be defined using contrast-to-noise ratio and modulation transfer function values that were similar to those of the reference CT scanners'. CBCT scanners with selected protocols can offer a viable alternative to CT scanners for acquiring STL models for virtual surgical planning at a lower effective dose., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Institute of Radiology and the International Association of Dentomaxillofacial Radiology.)

Aims: High-power-short-duration (HPSD) ablation is an effective treatment for atrial fibrillation but poses risks of thermal injuries to the oesophagus and vagus nerve. This study aims to investigate incidence and predictors of thermal injuries, employing machine learning., Methods and Results: A prospective observational study was conducted at Leipzig Heart Centre, Germany, excluding patients with multiple prior ablations. All patients received Ablation Index-guided HPSD ablation and subsequent oesophagogastroduodenoscopy. A machine learning algorithm categorized ablation points by atrial location and analysed ablation data, including Ablation Index, focusing on the posterior wall. The study is registered in clinicaltrials.gov (NCT05709756). Between February 2021 and August 2023, 238 patients were enrolled, of whom 18 (7.6%; nine oesophagus, eight vagus nerve, one both) developed thermal injuries, including eight oesophageal erythemata, two ulcers, and no fistula. Higher mean force (15.8 ± 3.9 g vs. 13.6 ± 3.9 g, P = 0.022), ablation point quantity (61.50 ± 20.45 vs. 48.16 ± 19.60, P = 0.007), and total and maximum Ablation Index (24 114 ± 8765 vs. 18 894 ± 7863, P = 0.008; 499 ± 95 vs. 473 ± 44, P = 0.04, respectively) at the posterior wall, but not oesophagus location, correlated significantly with thermal injury occurrence. Patients with thermal injuries had significantly lower distances between left atrium and oesophagus (3.0 ± 1.5 mm vs. 4.4 ± 2.1 mm, P = 0.012) and smaller atrial surface areas (24.9 ± 6.5 cm2 vs. 29.5 ± 7.5 cm2, P = 0.032)., Conclusion: The low thermal lesion's rate (7.6%) during Ablation Index-guided HPSD ablation for atrial fibrillation is noteworthy. Machine learning based ablation data analysis identified several potential predictors of thermal injuries. The correlation between machine learning output and injury development suggests the potential for a clinical tool to enhance procedural safety., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

The formation of a topological superconducting phase in a quantum-dot-based Kitaev chain requires nearest neighbor crossed Andreev reflection and elastic cotunneling. Here, we report on a hybrid InSb nanowire in a three-site Kitaev chain geometry-the smallest system with well-defined bulk and edge-where two superconductor-semiconductor hybrids separate three quantum dots. We demonstrate pairwise crossed Andreev reflection and elastic cotunneling between both pairs of neighboring dots and show sequential tunneling processes involving all three quantum dots. These results are the next step toward the realization of topological superconductivity in long Kitaev chain devices with many coupled quantum dots.

Statement of Problem: Accurate implant placement is essential for the success of dental implants. This placement influences osseointegration and occlusal forces. The freehand technique, despite its cost-effectiveness and time efficiency, may result in significant angular deviations compared with guided implantation, but the effect of angular deviations on the stress-strain state of peri-implant bone is unclear., Purpose: The purpose of this finite element analysis (FEA) study was to examine the effects of angular deviations on stress-strain states in peri-implant bone., Material and Methods: Computational modeling was used to investigate 4 different configurations of dental implant positions, each with 3 angles of insertion. The model was developed using computed tomography images, and typical mastication forces were considered. Strains were analyzed using the mechanostat hypothesis., Results: The location of the implant had a significant impact on bone strain intensity. An angular deviation of ±5 degrees from the planned inclination did not significantly affect cancellous bone strains, which primarily support the implant. However, it had a substantial effect on strains in the cortical bone near the implant. Such deviations also significantly influenced implant stresses, especially when the support from the cortical bone was uneven or poorly localized., Conclusions: In extreme situations, angular deviations can lead to overstraining the cortical bone, risking implant failure from unfavorable interaction with the implant. Accurate implant placement is essential to mitigate these risks., (Copyright © 2023 Editorial Council for The Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Tunneling spectroscopy is widely used to examine the subgap spectra in semiconductor-superconductor nanostructures when searching for Majorana zero modes (MZMs). Typically, semiconductor sections controlled by local gates at the ends of hybrids serve as tunnel barriers. Besides detecting states only at the hybrid ends, such gate-defined tunnel probes can cause the formation of non-topological subgap states that mimic MZMs. Here, we develop an alternative type of tunnel probes to overcome these limitations. After the growth of an InSb-Al hybrid nanowire, a precisely controlled in-situ oxidation of the Al shell is performed to yield a nm-thick AlOx layer. In such thin isolating layer, tunnel probes can be arbitrarily defined at any position along the hybrid nanowire by shadow-wall angle-deposition of metallic leads. In this work, we make multiple tunnel probes along single nanowire hybrids and successfully identify Andreev bound states (ABSs) of various spatial extension residing along the hybrids., (© 2023. Springer Nature Limited.)

Purpose Resuscitation guidelines have advocated the use of virtual learning as a form of pre-course e-learning. Virtual reality (VR) has been identified to provide a method of constructive learning with instant feedback. There are increasing publications of VR use in cardiopulmonary resuscitation (CPR) training; however, there is a dearth from the dental profession. Therefore, the aim of this exploratory study was to investigate dental students' opinions in CPR training using VR.Methods In total, 120 dental students undertook both conventional (manikin) and VR CPR training in a cross-over design. The VR scenario was in a hospital setting. Following, students completed a questionnaire evaluating their experiences.Results The majority of students (n = 88) reported that this was the first time that they had utilised VR. The experience of using VR in CPR training was rated as very good. Most students felt that the inclusion of VR in CPR training created a better learning experience and had a high learning potential. However, the hospital setting was not entirely relevant.Conclusion Dental students recommended that VR CPR training should be used as an adjunct to conventional training in dental education, but the VR scenario would benefit being a virtual dental environment., (© 2023. The Author(s).)

Background: Intensive forms of outreach mental health care (IOC) such as crisis resolution or home treatment teams are increasingly implemented as alternatives to inpatient admission, providing recovery-oriented treatment at home at comparable costs and outcomes. However, one issue with IOC is the lack of continuity regarding staff members who provide home visits, complicating relationship building and meaningful therapeutic exchange. The aim of this study is to validate existing primarily qualitative findings using performance data and to explore a possible correlation between the number of staff involved within IOC treatment and the service users' length of stay (LOS)., Methods: Routine data from an IOC team in a catchment area in Eastern Germany were analyzed. Basic parameters of service delivery were calculated and an in-depth descriptive analysis regarding staff continuity was performed. Further, an exploratory single case analysis was conducted, presenting the exact sequence of all treatment contacts for one case with low and one with high staff continuity., Results: We analyzed 10.598 face-to-face treatment contacts based on 178 IOC users. The mean LOS was 30.99 days. About 75% of all home visits were conducted by two or more staff members simultaneously. Service users saw an average of 10.24 different staff per treatment episode. On 11% of the care days, only unknown staff, and on 34% of the care days at least one unknown staff member conducted the home visit. 83% of the contacts were performed by the same three staff members and 51% were made by one and the same staff member. A significant positive correlation ( p  = 0.0007) was found between the number of different practitioners seen by a service user in the first seven days of care and the LOS., Conclusion: Our results suggest that a high number of different staff in the early period of IOC episodes correlates with an extended LOS. Future research must clarify the exact mechanisms of this correlation. Furthermore, it should be investigated how the multiple professions within IOC teams influence the LOS and the quality of treatment and what quality indicators may be suitable to ensure treatment processes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Schwarz, Wolff, Heinze, von Peter and Habicht.)

Background: Internationally, intensive psychiatric home treatment has been increasingly implemented as a community-based alternative to inpatient admission. Since 2018, the so-called Inpatient Equivalent Home Treatment (IEHT; German: "Stationsäquivalente Behandlung", short: "StäB") has been introduced as a particularly intensive form of home treatment that provides at least one daily treatment contact in the service users' (SU) home environment. Prior research shows that this can be challenging in rural catchment areas. Our paper investigates to which extent the location of the SU home location within the catchment area as well as the distance between the home and the clinic influence the utilisation of inpatient treatment compared to IEHT., Method: Routine data of one psychiatric hospital in the federal state of Brandenburg in Germany were analysed for the observational period 07/2018-06/2021. Two comparison groups were formed: SU receiving inpatient treatment and SU receiving IEHT. The SU places of residence were respectively anonymised and converted into geo-coordinates. A geographic information system (GIS) was used to visualise the places of residence, and car travel distances as well as travel times to the clinic were determined. Spatial analyses were performed to show the differences between comparison groups. In a more in-depth analysis, the proximity of SU residences to each other was examined as an indicator of possible clustering., Results: During the observational period, the location of 687 inpatient and 140 IEHT unique SU were mapped using the GIS. SU receiving treatment resided predominantly within the catchment area, and this proportion was slightly higher for SU receiving IEHT than for those treated in inpatient setting (95.3% vs. 84.7%). In the catchment area, the geographical distribution of SU place of residence was similar in the two groups. There was a general higher service provision in the more densely populated communities close to Berlin. SU with residence in peripheral communities were mainly treated within the inpatient setting. The mean travel times and distances to the place of residence only differed minimally between the two groups of SU (p > 0.05). The places of residence of SU treated with IEHT were located in greater proximity to each other than those of SU treated in inpatient setting (p < 0.1)., Conclusion: In especially peripheral parts of the examined catchment area, it may be more difficult to have access to IEHT rather than to inpatient services. The results raise questions regarding health equity and the planning of health care services and have important implications for the further development of intensive home treatment. Telehealth interventions such as blended-care approaches and an increase of flexibility in treatment intensity, e.g. eliminating the daily visit requirement, could ease the implementation of intensive home treatment especially in rural areas., (© 2022. The Author(s).)

Off-label drug prescribing in psychiatry is increasing. Many psychotropic drugs are approved for psychopathologic syndromes rather than based on international standard diagnostic classification systems which might facilitate the clinical decision for off-label prescriptions. The objective of this study was to analyze the prevalence and category of off-label use of psychotropic drugs. The study was conducted in 10 psychiatric hospitals in Germany over a period of 2 years. Prescription data of all patients were retrospectively analyzed after identification of antidepressants, antipsychotics, and mood-stabilizers, which were classified as off-label according to the German prescribing information and diagnostic classification according to ICD-10. In total, 53,909 patient cases (46% female) with a mean age of 46.8 (SD: 18) years were included in the study. 30.2% of the cases received at least one off-label prescription of a psychotropic drug during hospital stay. Off-label prevalence rates differed markedly between different diagnostic groups (ICD-10 F0/G3: 47%, F1: 33%, F2: 25%, F3: 21%, F4: 27%, F6: 46%, F7: 84%). The most often off-label prescribed drugs were quetiapine and mirtazapine for organic mental disorders (F0/G3), valproate and quetiapine in patients with disorders due to psychoactive substance use (F1), valproate in patients with psychotic disorders (F2), and risperidone and olanzapine in patients with affective disorders (F3). The prevalence rate of psychotropic off-label prescriptions is high if restricted to product description and ICD-10 diagnosis. Therefore, current psychiatric guidelines should drug-specifically issue this problem by defining psychiatric off-label indications based on a clear benefit-risk assessment., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Computer-assisted surgery (CAS) allows clinicians to personalize treatments and surgical interventions and has therefore become an increasingly popular treatment modality in maxillofacial surgery. The current maxillofacial CAS consists of three main steps: (1) CT image reconstruction, (2) bone segmentation, and (3) surgical planning. However, each of these three steps can introduce errors that can heavily affect the treatment outcome. As a consequence, tedious and time-consuming manual post-processing is often necessary to ensure that each step is performed adequately. One way to overcome this issue is by developing and implementing neural networks (NNs) within the maxillofacial CAS workflow. These learning algorithms can be trained to perform specific tasks without the need for explicitly defined rules. In recent years, an extremely large number of novel NN approaches have been proposed for a wide variety of applications, which makes it a difficult task to keep up with all relevant developments. This study therefore aimed to summarize and review all relevant NN approaches applied for CT image reconstruction, bone segmentation, and surgical planning. After full text screening, 76 publications were identified: 32 focusing on CT image reconstruction, 33 focusing on bone segmentation and 11 focusing on surgical planning. Generally, convolutional NNs were most widely used in the identified studies, although the multilayer perceptron was most commonly applied in surgical planning tasks. Moreover, the drawbacks of current approaches and promising research avenues are discussed.

Objective: Cone beam computed tomography (CBCT) images are being increasingly used to acquire three-dimensional (3D) models of the skull for additive manufacturing purposes. However, the accuracy of such models remains a challenge, especially in the orbital area. The aim of this study is to assess the impact of four different CBCT imaging positions on the accuracy of the resulting 3D models in the orbital area., Methods: An anthropomorphic head phantom was manufactured by submerging a dry human skull in silicon to mimic the soft tissue attenuation and scattering properties of the human head. The phantom was scanned on a ProMax 3D MAX CBCT scanner using 90 and 120 kV for four different field of view positions: standard; elevated; backwards tilted; and forward tilted. All CBCT images were subsequently converted into 3D models and geometrically compared with a "gold-standard" optical scan of the dry skull., Results: Mean absolute deviations of the 3D models ranged between 0.15 ± 0.11 mm and 0.56 ± 0.28 mm. The elevated imaging position in combination with 120 kV tube voltage resulted in an improved representation of the orbital walls in the resulting 3D model without compromising the accuracy., Conclusions: Head positioning during CBCT imaging can influence the accuracy of the resulting 3D model. The accuracy of such models may be improved by positioning the region of interest ( e.g. the orbital area) in the focal plane (Figure 2a) of the CBCT X-ray beam.

Background: Nursing staff were excluded from the German DRG system for somatic hospital treatment and will be funded separately in the future. In psychiatry and psychosomatic medicine, binding personnel requirements have been defined but there has been no regulation of how these personnel requirements are adequately financed., Objective: The objective of this study was to analyze the costs of inpatient psychiatry and psychosomatic medicine and to evaluate possible effects of funding nursing staff separately., Material and Methods: This analysis is based on aggregated daily treatment costs of selected hospitals (data year 2018), which annually submit their performance and cost data to the Institute for the Hospital Remuneration System (InEK) for the empirical further development of the remuneration system., Results: Nursing staff represent the largest cost factor in inpatient psychiatry and psychosomatic medicine. Excluding nursing staff drastically reduces the variance of psychiatric DRG renumeration and even exceeds its proportion of the total costs. After outsourcing nursing costs, psychiatric DRGs achieve only a very limited cost separation., Conclusion: The binding personnel requirements necessitate adequate financing of nursing staff. This raises the debate about the further development of psychiatric remuneration. The question arises as to whether the effort associated with using the psychiatric DRG system justifies its usefulness as an instrument for budgeting when core functions such as cost separation are only given to a limited extent. Alternative approaches to budgeting should also be examined for putting costs and benefits in a better ratio., (© 2021. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Sustainable forest management requires understanding of ecosystem phosphorus (P) cycling. Lang et al. (2017) [ Biogeochemistry, https://doi.org/10.1007/s10533-017-0375-0] introduced the concept of P-acquiring vs. P-recycling nutrition strategies for European beech ( Fagus sylvatica L. ) forests on silicate parent material, and demonstrated a change from P-acquiring to P-recycling nutrition from P-rich to P-poor sites. The present study extends this silicate rock-based assessment to forest sites with soils formed from carbonate bedrock. For all sites, it presents a large set of general soil and bedrock chemistry data. It thoroughly describes the soil P status and generates a comprehensive concept on forest ecosystem P nutrition covering the majority of Central European forest soils. For this purpose, an Ecosystem P Nutrition Index ( ENI P ) was developed, which enabled the comparison of forest P nutrition strategies at the carbonate sites in our study among each other and also with those of the silicate sites investigated by Lang et al. (2017). The P status of forest soils on carbonate substrates was characterized by low soil P stocks and a large fraction of organic Ca-bound P (probably largely Ca phytate) during early stages of pedogenesis. Soil P stocks, particularly those in the mineral soil and of inorganic P forms, including Al- and Fe-bound P, became more abundant with progressing pedogenesis and accumulation of carbonate rock dissolution residue. Phosphorus-rich impure, silicate-enriched carbonate bedrock promoted the accumulation of dissolution residue and supported larger soil P stocks, mainly bound to Fe and Al minerals. In carbonate-derived soils, only low P amounts were bioavailable during early stages of pedogenesis, and, similar to P-poor silicate sites, P nutrition of beech forests depended on tight (re)cycling of P bound in forest floor soil organic matter (SOM). In contrast to P-poor silicate sites, where the ecosystem P nutrition strategy is direct biotic recycling of SOM-bound organic P, recycling during early stages of pedogenesis on carbonate substrates also involves the dissolution of stable Ca-P org precipitates formed from phosphate released during SOM decomposition. In contrast to silicate sites, progressing pedogenesis and accumulation of P-enriched carbonate bedrock dissolution residue at the carbonate sites promote again P-acquiring mechanisms for ecosystem P nutrition., Supplementary Information: The online version contains supplementary material available at 10.1007/s10533-021-00884-7., Competing Interests: Conflict of interestThe authors have no conflicts of interest to declare that are relevant to the content of this article., (© The Author(s) 2022.)

Purpose: The aim of this study was to analyze the epidemiology of polypharmacy in hospital psychiatry. Another aim was to investigate predictors of the number of drugs taken and the associated risks of drug-drug interactions and potentially inappropriate medications in the elderly., Methods: Daily prescription data were obtained from a pharmacovigilance project sponsored by the Innovations Funds of the German Federal Joint Committee., Results: The study included 47 071 inpatient hospital cases from eight different study centers. The mean number of different drugs during the entire stay was 6.1 (psychotropic drugs = 2.7; others = 3.4). The mean number of drugs per day was 3.8 (psychotropic drugs = 1.6; others = 2.2). One third of cases received at least five different drugs per day on average during their hospital stay (polypharmacy). Fifty-one percent of patients received more than one psychotropic drug simultaneously. Hospital cases with polypharmacy were 18 years older (p < 0.001), more likely to be female (52% vs. 40%, p < 0.001) and had more comorbidities (5 vs. 2, p < 0.001) than hospital cases without polypharmacy. The risks of drug-drug interactions (OR = 3.7; 95% CI = 3.5-3.9) and potentially inappropriate medication use in the elderly (OR = 2.2; CI = 1.9-2.5) substantially increased in patients that received polypharmacy., Conclusion: Polypharmacy is frequent in clinical care. The number of used drugs is a proven risk factor of adverse drug reactions due to drug-drug interactions and potentially inappropriate medication use in the elderly. The potential interactions and the specific pharmacokinetics and -dynamics of older patients should always be considered when multiple drugs are used., (© 2021 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Background and Objective: Over the past decade, convolutional neural networks (CNNs) have revolutionized the field of medical image segmentation. Prompted by the developments in computational resources and the availability of large datasets, a wide variety of different two-dimensional (2D) and three-dimensional (3D) CNN training strategies have been proposed. However, a systematic comparison of the impact of these strategies on the image segmentation performance is still lacking. Therefore, this study aimed to compare eight different CNN training strategies, namely 2D (axial, sagittal and coronal slices), 2.5D (3 and 5 adjacent slices), majority voting, randomly oriented 2D cross-sections and 3D patches., Methods: These eight strategies were used to train a U-Net and an MS-D network for the segmentation of simulated cone-beam computed tomography (CBCT) images comprising randomly-placed non-overlapping cylinders and experimental CBCT images of anthropomorphic phantom heads. The resulting segmentation performances were quantitatively compared by calculating Dice similarity coefficients. In addition, all segmented and gold standard experimental CBCT images were converted into virtual 3D models and compared using orientation-based surface comparisons., Results: The CNN training strategy that generally resulted in the best performances on both simulated and experimental CBCT images was majority voting. When employing 2D training strategies, the segmentation performance can be optimized by training on image slices that are perpendicular to the predominant orientation of the anatomical structure of interest. Such spatial features should be taken into account when choosing or developing novel CNN training strategies for medical image segmentation., Conclusions: The results of this study will help clinicians and engineers to choose the most-suited CNN training strategy for CBCT image segmentation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier B.V.)

Introduction: The aim of this study was to describe the number and type of drugs used to treat depressive disorders in inpatient psychiatry and to analyse the determinants of potential drug-drug interactions (pDDI) and potentially inappropriate medication (PIM)., Methods: Our study was part of a larger pharmacovigilance project funded by the German Innovation Funds. It included all inpatients with a main diagnosis in the group of depressive episodes (F32, ICD-10) or recurrent depressive disorders (F33) discharged from eight psychiatric hospitals in Germany between 1 October 2017 and 30 September 2018 or between 1 January and 31 December 2019., Results: The study included 14,418 inpatient cases. The mean number of drugs per day was 3.7 (psychotropic drugs = 1.7; others = 2.0). Thirty-one percent of cases received at least five drugs simultaneously (polypharmacy). Almost one half of all cases received a combination of multiple antidepressant drugs (24.8%, 95% CI 24.1%-25.5%) or a treatment with antidepressant drugs augmented by antipsychotic drugs (21.9%, 95% CI 21.3%-22.6%). The most frequently used antidepressants were selective serotonin reuptake inhibitors, followed by serotonin and norepinephrine reuptake inhibitors and tetracyclic antidepressants. In multivariate analyses, cases with recurrent depressive disorders and cases with severe depression were more likely to receive a combination of multiple antidepressant drugs (Odds ratio recurrent depressive disorder: 1.56, 95% CI 1.41-1.70, severe depression 1.33, 95% CI 1.18-1.48). The risk of any pDDI and PIM in elderly patients increased substantially with each additional drug (Odds Ratio: pDDI 1.32, 95% CI: 1.27-1.38, PIM 1.18, 95% CI: 1.14-1.22) and severity of disease (Odds Ratio per point on CGI-Scale: pDDI 1.29, 95% CI: 1.11-1.46, PIM 1.27, 95% CI: 1.11-1.44), respectively., Conclusion: This study identified potential sources and determinants of safety risks in pharmacotherapy of depressive disorders and provided additional data which were previously unavailable. Most inpatients with depressive disorders receive multiple psychotropic and non-psychotropic drugs and pDDI and PIM are relatively frequent. Patients with a high number of different drugs must be intensively monitored in the management of their individual drug-related risk-benefit profiles., Competing Interests: Independent of the present study, KD received fees from Janssen Pharmaceuticals, Inc. for her consultancy work on the Neuroscience Steering Committee. CN received lecture and consultancy fees from Janssen-Cilag and Neuraxpharm as well as fees for conducting clinical studies from Janssen-Cilag. ST has received lecture fees from Janssen-Cilag, Otsuka / Lundbeck and Servier and is a member of the Advisory Board of Otsuka and Janssen-Cilag. CH has received lecture fees from Otsuka. The commercial funding sources were unrelated to the present study and did not alter our adherence to PLOS ONE policies on sharing data and materials.

High cone-angle artifacts (HCAAs) appear frequently in circular cone-beam computed tomography (CBCT) images and can heavily affect diagnosis and treatment planning. To reduce HCAAs in CBCT scans, we propose a novel deep learning approach that reduces the three-dimensional (3D) nature of HCAAs to two-dimensional (2D) problems in an efficient way. Specifically, we exploit the relationship between HCAAs and the rotational scanning geometry by training a convolutional neural network (CNN) using image slices that were radially sampled from CBCT scans. We evaluated this novel approach using a dataset of input CBCT scans affected by HCAAs and high-quality artifact-free target CBCT scans. Two different CNN architectures were employed, namely U-Net and a mixed-scale dense CNN (MS-D Net). The artifact reduction performance of the proposed approach was compared to that of a Cartesian slice-based artifact reduction deep learning approach in which a CNN was trained to remove the HCAAs from Cartesian slices. In addition, all processed CBCT scans were segmented to investigate the impact of HCAAs reduction on the quality of CBCT image segmentation. We demonstrate that the proposed deep learning approach with geometry-aware dimension reduction greatly reduces HCAAs in CBCT scans and outperforms the Cartesian slice-based deep learning approach. Moreover, the proposed artifact reduction approach markedly improves the accuracy of the subsequent segmentation task compared to the Cartesian slice-based workflow., (© 2021 Institute of Physics and Engineering in Medicine.)

The aim of the study was to estimate and to compare effective doses in the elbow region resulting from four different x-ray imaging modalities. Absorbed organ doses were measured using 11 metal oxide field effect transistor (MOSFET) dosimeters that were placed in a custom-made anthropomorphic elbow RANDO phantom. Examinations were performed using Shimadzu FH-21 HR radiography device, Siemens Sensation Open 24-slice MSCT-device, NewTom 5G CBCT device, and Planmed Verity CBCT device, and the effective doses were calculated according to ICRP 103 recommendations. The effective dose for the conventional radiographic device was 1.5 µSv. The effective dose for the NewTom 5G CBCT ranged between 2.0 and 6.7 µSv, for the Planmed Verity CBCT device 2.6 µSv and for the Siemens Sensation MSCT device 37.4 µSv. Compared with conventional 2D radiography, this study demonstrated a 1.4-4.6 fold increase in effective dose for CBCT and 25-fold dose for standard MSCT protocols. When compared with 3D CBCT protocols, the study showed a 6-19 fold increase in effective dose using a standard MSCT protocol. CBCT devices offer a feasible low-dose alternative for elbow 3D imaging when compared to MSCT., (© 2021 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Patient-specific approach is gaining a wide popularity in computational simulations of biomechanical systems. Simulations (most often based on the finite element method) are to date routinely created using data from imaging devices such as computed tomography which makes the models seemingly very complex and sophisticated. However, using a computed tomography in finite element calculations does not necessarily enhance the quality or even credibility of the models as these depend on the quality of the input images. Low-resolution (medical-)CT datasets do not always offer detailed representation of trabecular bone in FE models and thus might lead to incorrect calculation of mechanical response to external loading. The effect of image resolution on mechanical simulations of bone-implant interaction has not been thoroughly studied yet. In this study, the effect of image resolution on the modeling procedure and resulting mechanical strains in bone was analyzed on the example of cranial implant. For this purpose, several finite element models of bone interacting with fixation-screws were generated using seven computed tomography datasets of a bone specimen but with different image resolutions (ranging from micro-CT resolution of 25 μm to medical-CT resolution of 1250 μm). The comparative analysis revealed that FE models created from images of low resolution (obtained from medical computed tomography) can produce biased results. There are two main reasons: 1. Medical computed tomography images do not allow generating models with complex trabecular architecture which leads to substituting of the intertrabecular pores with a fictitious mass; 2. Image gray value distribution can be distorted resulting in incorrect mechanical properties of the bone and thus in unrealistic or even completely fictitious mechanical strains. The biased results of calculated mechanical strains can lead to incorrect conclusion, especially when bone-implant interaction is investigated. The image resolution was observed not to significantly affect stresses in the fixation screw itself; however, selection of bone material representation might result in significantly different stresses in the screw., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: The aim was to use routine data available at a patient's admission to the hospital to predict polypharmacy and drug-drug interactions (DDI) and to evaluate the prediction performance with regard to its usefulness to support the efficient management of benefits and risks of drug prescriptions., Design: Retrospective, longitudinal study., Setting: We used data from a large multicentred pharmacovigilance project carried out in eight psychiatric hospitals in Hesse, Germany., Participants: Inpatient episodes consecutively discharged between 1 October 2017 and 30 September 2018 (year 1) or 1 January 2019 and 31 December 2019 (year 2)., Outcome Measures: The proportion of rightly classified hospital episodes., Methods: We used gradient boosting to predict respective outcomes. We tested the performance of our final models in unseen patients from another calendar year and separated the study sites used for training from the study sites used for performance testing., Results: A total of 53 909 episodes were included in the study. The models' performance, as measured by the area under the receiver operating characteristic, was 'excellent' (0.83) and 'acceptable' (0.72) compared with common benchmarks for the prediction of polypharmacy and DDI, respectively. Both models were substantially better than a naive prediction based solely on basic diagnostic grouping., Conclusion: This study has shown that polypharmacy and DDI can be predicted from routine data at patient admission. These predictions could support an efficient management of benefits and risks of hospital prescriptions, for instance by including pharmaceutical supervision early after admission for patients at risk before pharmacological treatment is established., Competing Interests: Competing interests: Independent of the present study, KD received fees from Janssen Pharmaceuticals for her consultancy work on the Neuroscience Steering Committee. CN received lecture and consultancy fees from Janssen-Cilag and Neuraxpharm as well as fees for conducting clinical studies from Janssen-Cilag. CH has received lecture fees from Otsuka., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Many psychotropic drugs are listed as potentially inappropriate medication (PIM) in the older population. Potentially inappropriate means that prescription of those drugs in older adults may cause significant harm. The objective of this study was to analyze the prevalence and sort of PIM prescribing in a naturalistic, real-world psychiatric setting., Methods: The retrospective analysis gathered data from a large pharmacovigilance study, conducted at 10 psychiatric hospitals. Data from inpatients aged ≥ 65 years were included for the analysis. The number and sort of PIM, as defined by the German PRISCUS list, were controlled by analyzing the patients' medication profile., Results: In total, 4760 patient cases (59.2% female) with a mean (mean ± standard deviation (SD)) age of 77.33 ± 7.77 years were included into the study. Altogether, 1615 cases (33.9%) received at least 1 PRISCUS-PIM per day (regular and as-needed medication included). The most frequently prescribed PRISCUS-PIM (n = 2144) were zopiclone > 3.75 mg/day (n = 310), lorazepam > 2 mg/day (n = 269), haloperidol > 2 mg/day (n = 252), and diazepam (n = 182). Cases with PRISCUS-PIM were younger (75.7 vs. 78.2 years, p < 0.001) and had a longer (26 vs. 22 days, p < 0.001) hospital length of stay. Replacing benzodiazepines and z-substances, haloperidol > 2 mg, tricyclic antidepressants, first generation antihistaminergic drugs, and clonidine by non-PIM could reduce 69.9% of PRISCUS-PIM-prescribing., Conclusions: The prevalence of PRISCUS-PIM is high in the hospitalized psychiatric setting. Rational deprescribing of inappropriate anticholinergics, benzodiazepines, and antipsychotics in the older population is a key component to reduce the risk of adverse drug reactions. More tolerable medications should be prescribed.

At least 170 approved drugs are linked to QT prolongation, which can lead to serious adverse drug reactions (ADRs), such as Torsade de Pointes (TdP). The aim of this study was to analyze the prevalence and type of pharmacodynamic drug-drug interactions (DDIs) between QT-prolonging drugs in psychiatry. The present retrospective analysis used data from a large pharmacovigilance study, conducted in 10 psychiatric hospitals in Germany. Patients medication lists were screened for QT-prolonging drugs, classified according to the Arizona Center for Education and Research on Therapeutics (AZCERT). In total, 27,396 patient cases (46% female) with a mean (± standard deviation) age of 47 ± 18 years were included in the study. Altogether, 83% of the cases received at least one and up to eight QT-prolonging drugs at the same time. Combination of drugs with a known or possible risk for TdP (according to the AZCERT) was detected in 13,670 cases (50%). Most frequently prescribed psychotropic high-risk drugs (n = 48,995) were the antipsychotics pipamperone (n = 6202), quetiapine (n = 5718), prothipendyl (n = 4298), and risperidone (n = 4265). The replacement of high-risk drugs such as tricyclic antidepressants, levomepromazine, melperone, and promethazine with more tolerable drugs could avoid 11% of QT-prolonging drugs and increase the tolerability of psychopharmacological treatment. More than 80% of psychiatric patients receive at least one QT-prolonging drug during their hospital stay, and almost 50% of these drugs are combined in clinical practice. For the prevention of cardiac ADRs, the physician should evaluate the risk for QT prolongation for each drug and patient-specific risk factors before prescribing these drugs or drug combinations.

Due to the high number of psychotropic drugs with anticholinergic potential, patients taking psychotropic drugs are at high risk for anticholinergic adverse drug reactions (ADRs). The aim of this study was to analyze the prevalence and type of pharmacodynamic anticholinergic drug-drug interactions in psychiatric patients. The retrospective longitudinal analysis used data from a large pharmacovigilance study conducted in ten German psychiatric hospitals. Anticholinergic burden of drugs was defined as "strong" or "moderate" based on current literature. Number and type of anticholinergic drugs were assessed. In total, 27,396 patient cases (45.6% female) with a mean age of 47.3 ± 18.3 years were included. 17.4% (n = 4760) of patients were ≥ 64 years. 35.4% of the patients received between one and four anticholinergic drugs simultaneously. A combination of drugs with anticholinergic potential was detected in 1738 cases (6.3%). Most prescribed drugs were promethazine (n = 2996), olanzapine (n = 2561), biperiden (n = 1074), and doxepin (n = 963). Patients receiving anticholinergic combinations were younger (45.7 vs. 47.4 years, p < 0.01) and had a longer inpatient stay (median 18 vs. 26.5 days, p < 0.001). The prevalence of anticholinergic drug use in psychiatry is high. Further efforts need to focus on reducing the rate of anticholinergics and inappropriate medication especially in the elderly. Anticholinergic ADRs can be prevented by avoiding high-risk drug combinations. Replacing tricyclic antidepressants and first-generation antihistamines with drugs with lower anticholinergic potential and avoiding biperiden could reduce 59.3% of anticholinergic drug application.

Information on the bioavailability and -accessibility of subsoil phosphorus (P) and how soil moisture affects its utilization by plants is scarce. The current study examined whether and to which degree wheat acquires P from subsoil allocated hydroxyapatite and how this could be affected by soil moisture. We investigated the 33 P uptake by growing wheat in two rhizotron trials (soil and sand) with integrated 33 P-labelled hydroxyapatite hotspots over a period of 44 days using digital autoradiography imaging and liquid scintillation counting. We applied two irrigation scenarios, mimicking either rainfall via topsoil watering or subsoil water storage. The plants showed similar biomass development when grown in soil, but a reduced growth in sand rhizotrons. Total plant P (tot) stocks were significantly larger in plants grown under improved subsoil moisture supply, further evidenced by enhanced P stocks in the ears of wheat in the sand treatment due to an earlier grain filling. This P uptake is accompanied by larger 33 P signals, indicating that the plants accessed the hydroxyapatite because subsoil irrigation also promoted root proliferation within and around the hotspots. We conclude that even within a single season plants access subsoil mineral P sources, and this process is influenced by water management.

Background: The individual needs of patients are central to hospital care. Due to the resulting complexity grouping of patients with similar therapeutic needs seems to facilitate an efficient organization of processes and the required treatment resources in hospital care., Objective: The aim of this study was to develop a system of disorder-related, treatment-oriented case groups as a possible tool for the efficient and needs-based organization of hospital care., Material and Methods: The disorder-related groups were developed in a multistage, mixed-methods design. The technical content and quantitative description of the case groups and the extent of treatment included all consecutive inpatient treatment cases discharged between 1 January 2017 and 31 December 2017 from 9 psychiatric hospitals in Hesse, Germany., Results: All diagnoses in chapter F of the German modification of the International Statistical Classification of Diseases 10 (ICD-10-GM) were grouped into a total of 10 disorder-related groups. Analyses included 20,252 inpatient hospital treatment cases. Substantial management-relevant differences between the case groups could be identified and the various case group-specific configurations of clinically relevant comorbidities could be demonstrated., Discussion: The presented disorder-related grouping system and configuration of comorbidities suggest a modular organization of therapeutic measures and constitute a promising basis for needs-based management of patient care. Future work will show to what degree the disorder-related groups can facilitate a needs-specific treatment and align economic and therapeutic interests of psychiatric care.

Psychiatric patients are high-risk patients for the development of pharmacokinetic drug-drug interactions (DDIs), leading to highly variable (victim) drug serum concentrations. Avoiding and targeting high-risk drug combinations could reduce preventable adverse drug reactions (ADRs). Pharmacokinetic cytochrome P450 (CYP)-mediated DDIs are often predictable and, therefore, preventable. The retrospective, longitudinal analysis used informations from a large pharmacovigilance study (Optimization of pharmacological treatment in hospitalized psychiatric patients study, study number 01VSF16009, 01/2017), conducted in 10 psychiatric hospitals in Germany. Medication data were examined for the co-prescription of clinically relevant CYP inhibitors or inducers and substrates of these enzymes (victim drugs). In total, data from 27,396 patient cases (45.6% female) with a mean (mean ± standard deviation (SD)) age of 47.3 ± 18.3 years were available for analysis. CYP inhibitors or inducers were at least once prescribed in 14.4% (n = 3946) of the cases. The most frequently prescribed CYP inhibitors were melperone (n = 2504, 28.1%) and duloxetine (n = 1324, 14.9%). Overall, 51.0% of the cases taking melperone were combined with a victim drug (n = 1288). Carbamazepine was the most frequently prescribed CYP inducer (n = 733, 88.8%). Combinations with victim drugs were detected for 58% (n = 427) of cases on medication with carbamazepine. Finally, a DDI was detected in 43.6% of the cases in which a CYP inhibitor or inducer was prescribed. The frequency of CYP-mediated DDI is considerably high in the psychiatric setting. Physicians should be aware of the CYP inhibitory and inducing potential of psychotropic and internistic drugs (especially, melperone).

Background: Post-traumatic stress disorder is likely to affect clinical courses in the somatic hospital ward when appearing as comorbidity. Thus, this study aimed to assess the costs associated with comorbid post-traumatic stress disorder in a somatic hospital and to analyze if reimbursement appropriately compensated additional costs., Methods: The study used data from a German university hospital between 2011 and 2014, analyzing 198,819 inpatient episodes. Inpatient's episodes were included for analysis if they had a somatic primary diagnosis and a secondary diagnosis of post-traumatic stress disorder. Costs were calculated based on resource use and compared to reimbursement. Analyses were adjusted for sex, age and somatic comorbidities., Results: N = 219 Inpatient's episode were found with primary somatic disorder and a comorbid post-traumatic stress disorder. Inpatients episodes with comorbid post-traumatic stress disorder were compared to 34,229 control episodes, which were hospitalized with the same main diagnosis. Post-traumatic stress disorder was associated with additional hospital costs of €2311 [95%CI €1268 - €3355], while reimbursement rose by €1387 [€563 - €2212]. Results indicate that extra costs associated with post-traumatic stress disorder are not fully reimbursed. Male patients showed higher hospital costs associated with post-traumatic stress disorder. On average, post-traumatic stress disorder was associated with an extra length of stay of 3.4 days [2.1-4.6 days]., Conclusion: Costs associated with post-traumatic stress disorder were substantial and exceeded reimbursement, indicating an inadequate reimbursement for somatic patients with comorbid post-traumatic stress disorder.

Background: Intensive care units represent one of the largest clinical cost centers in hospitals. Mechanical ventilation accounts for a significant share of this cost. There is a relative dearth of information quantifying the impact of ventilation on daily ICU cost. We thus determine daily costs of ICU care, incremental cost of mechanical ventilation per ICU day, and further differentiate cost by underlying diseases., Methods: Total ICU costs, length of ICU stay, and duration of mechanical ventilation of all 10,637 adult patients treated in ICUs at a German hospital in 2013 were analyzed for never-ventilated patients (N = 9181), patients ventilated at least 1 day, (N = 1455) and all patients (N = 10,637). Total ICU costs were regressed on the number of ICU days. Finally, costs were analyzed separately by ICD-10 chapter of main diagnosis., Results: Daily non-ventilated costs were €999 (95%CI €924 - €1074), and ventilated costs were €1590 (95%CI €1524 - €1657), a 59% increase. Costs per non-ventilated ICU day differed substantially and were lowest for endocrine, nutritional or metabolic diseases (€844), and highest for musculoskeletal diseases (€1357). Costs per ventilated ICU day were lowest for diseases of the circulatory system (€1439) and highest for cancer patients (€1594). The relative cost increase due to ventilation was highest for diseases of the respiratory system (94%) and even non-systematic for patients with musculoskeletal diseases (13%, p = 0.634)., Conclusions: Results show substantial variability of ICU costs for different underlying diseases and underline mechanical ventilation as an important driver of ICU costs.

Post-kala-azar dermal leishmaniasis may occur after successful treatment of visceral leishmaniasis and is characterized by macules, papules, or nodules in the skin, with varying size. The response to antileishmanial therapy remains difficult to assess because there are presently no reliable biomarkers. To date, skin lesions are clinically assessed for decrease in size or change in color, which is invariably subjective. Novel 3-dimensional optical scanning devices offer safe and field-adapted methods to objectively assess skin lesions for changes over time in size and color that can be quantified with great accuracy.

Purpose: In order to attain anatomical models, surgical guides and implants for computer-assisted surgery, accurate segmentation of bony structures in cone-beam computed tomography (CBCT) scans is required. However, this image segmentation step is often impeded by metal artifacts. Therefore, this study aimed to develop a mixed-scale dense convolutional neural network (MS-D network) for bone segmentation in CBCT scans affected by metal artifacts., Method: Training data were acquired from 20 dental CBCT scans affected by metal artifacts. An experienced medical engineer segmented the bony structures in all CBCT scans using global thresholding and manually removed all remaining noise and metal artifacts. The resulting gold standard segmentations were used to train an MS-D network comprising 100 convolutional layers using far fewer trainable parameters than alternative convolutional neural network (CNN) architectures. The bone segmentation performance of the MS-D network was evaluated using a leave-2-out scheme and compared with a clinical snake evolution algorithm and two state-of-the-art CNN architectures (U-Net and ResNet). All segmented CBCT scans were subsequently converted into standard tessellation language (STL) models and geometrically compared with the gold standard., Results: CBCT scans segmented using the MS-D network, U-Net, ResNet and the snake evolution algorithm demonstrated mean Dice similarity coefficients of 0.87 ± 0.06, 0.87 ± 0.07, 0.86 ± 0.05, and 0.78 ± 0.07, respectively. The STL models acquired using the MS-D network, U-Net, ResNet and the snake evolution algorithm demonstrated mean absolute deviations of 0.44 mm ± 0.13 mm, 0.43 mm ± 0.16 mm, 0.40 mm ± 0.12 mm and 0.57 mm ± 0.22 mm, respectively. In contrast to the MS-D network, the ResNet introduced wave-like artifacts in the STL models, whereas the U-Net incorrectly labeled background voxels as bone around the vertebrae in 4 of the 9 CBCT scans containing vertebrae., Conclusion: The MS-D network was able to accurately segment bony structures in CBCT scans affected by metal artifacts., (© 2019 The Authors. Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Background: Hospital-acquired infections have not only gained increasing attention clinically, but also methodologically, as a time-varying exposure. While methods to appropriately estimate extra length of stay (LOS) have been established and are increasingly used in the literature, proper estimation of cost figures has lagged behind., Methods: Analysing the additional costs and reimbursements of Clostridium difficile -infections (CDI), we use a within-main-diagnosis-time-to-exposure stratification approach to incorporate time-varying exposures in a regression model, while at the same time accounting for cost clustering within diagnosis groups., Results: We find that CDI is associated with €9000 of extra costs, €7800 of higher reimbursements, and 6.4 days extra length of stay. Using a conventional method, which suffers from time-dependent bias, we derive estimates more than three times as high (€23,000, €8000, 21 days respectively). We discuss our method in the context of recent methodological advances in the estimation of the costs of hospital-acquired infections., Conclusions: CDI is associated with sizeable in-hospital costs. Neglecting the methodological particularities of hospital-acquired infections can however substantially bias results. As the data needed for an appropriate analysis are collected routinely in most hospitals, we recommend our approach as a feasible way for estimating the economic impact of time-varying adverse events during hospital stay., Competing Interests: Competing interestsThe authors declare that they have no competing interests.

This study investigated the effect of implant thickness and material on deformation and stress distribution within different components of cranial implant assemblies. Using the finite element method, two cranial implants, differing in size and shape, and thicknesses (1, 2, 3 and 4 mm, respectively), were simulated under three loading scenarios. The implant assembly model included the detailed geometries of the mini-plates and micro-screws and was simulated using a sub-modeling approach. Statistical assessments based on the Design of Experiment methodology and on multiple regression analysis revealed that peak stresses in the components are influenced primarily by implant thickness, while the effect of implant material is secondary. On the contrary, the implant deflection is influenced predominantly by implant material followed by implant thickness. The highest values of deformation under a 50 N load were observed in the thinnest (1 mm) Polymethyl Methacrylate implant (Small defect: 0.296 mm; Large defect: 0.390 mm). The thinnest Polymethyl Methacrylate and Polyether Ether Ketone implants also generated stresses in the implants that can potentially breach the materials' yield limit. In terms of stress distribution, the change of implant thickness had a more significant impact on the implant performance than the change of Young's modulus of the implant material. The results indicated that the stresses are concentrated in the locations of fixation; therefore, the detailed models of mini-plates and micro-screws implemented in the finite element simulation provided a better insight into the mechanical performance of the implant-skull system., (Copyright © 2019. Published by Elsevier Ltd.)

Polymethyl methacrylate (PMMA), an easily moldable and economical synthetic resin, has been used since the 1940s. In addition, PMMA has good mechanical properties and is one of the most biocompatible alloplastic materials currently available. The PMMA can serve as a spacer and as a delivery vehicle for antibiotics. Prior studies have indicated that no significant differences in infection rates exist between autologous and acrylic cranioplasty. Although inexpensive, the free-hand cranioplasty technique often yields unsatisfactory cosmetic results. In the present study, the application of a recently developed, economic modality for the perioperative application, and molding of PMMA to ensure a precise fit in 16 patients using computer-aided design, computer-aided manufacturing, and rapid prototyping was described.The mean defect size was 102.0 ± 26.4 cm. The mean volume of PMMA required to perform the cranioplasty procedure was 51 mL. The cost of PMMA was approximately 6 Euro (&OV0556;) per mL. The costs of fabricating the implants varied from 119.8 &OV0556; to 1632.0 &OV0556; with a mean of 326.4 &OV0556; ± 371.6. None of the implants required removal during the follow-up period.

Purpose: Mild traumatic brain injury (TBI) is common but accurate diagnosis and its clinical consequences have been a problem. Maxillofacial trauma does have an association with TBI. Neuron-specific enolase (NSE) has been developed to evaluate neuronal damage. The objective of this study was to investigate the accuracy of NSE serum levels to detect mild brain injury of patients with sustained maxillofacial fractures during motor vehicle accidents., Methods: Blood samples were drawn from 40 healthy people (control group) and 48 trauma patients who had sustained isolated maxillofacial fractures and mild brain injury in motor vehicle accidents. Brain injuries were graded by Glasgow Coma Scale. In the trauma group, correlations between the NSE serum value and different facial fracture sites were also assessed., Results: The NSE serum level (mean ± SD, ng/ml) in the 48 patients with maxillofacial fractures and mild TBI was 13.12 ± 9.68, significantly higher than that measured in the healthy control group (7.72 ± 1.82, p < 0.001). The mean NSE serum level (ng/ml) in the lower part of the facial skeleton (15.44 with SD 15.34) was higher than that in the upper facial part (12.42 with SD 7.68); and the mean NSE level (ng/ml) in the middle-and lower part (11.97 with SD 5.63) was higher than in the middle part (7.88 with SD 2.64)., Conclusion: An increase in NSE serum levels can be observed in patients sustained maxillofacial fractures and mild brain injury., (Copyright © 2019 Daping Hospital and the Research Institute of Surgery of the Third Military Medical University. Production and hosting by Elsevier B.V. All rights reserved.)

Purpose: To evaluate possible risk factors associated with wound dehiscences following pre-implant alveolar bone augmentation with autologous anterior iliac crest bone grafts covered with resorbable collagen membranes or human demineralised bone laminae., Materials and Methods: Data of 161 patients who underwent bone augmentation prior to the insertion of dental implants were analysed. The preoperative dental status, locations of alveolar bone augmentation sites and location of wound dehiscences were recorded. Gender, age, smoking, alcohol exposure, and dental and medical histories were reviewed. Information was also collected on the surgeons, augmentation technique, application of a collagen membrane, fixation screw type and suture material. Univariate logistic regression analysis was used to evaluate pre- and perioperative variables as predictors of dehiscences., Results: A total of 42 (26.1%) of the 161 augmented patients developed a wound dehiscence following surgery. Most commonly affected sites were the anterior maxilla, followed by the anterior mandible. Males developed wound dehiscences with higher probability than females (odds ratio female = 0.444; P = 0.025; 95% CI: 0.214 to 0.903). Furthermore, marginal associations (P < 0.10) are found for smoking and an anterior location of the augmentation. Smokers were found to have higher probability of a wound dehiscence (odds ratio 2.089; P = 0.064; 95% CI: 0.957 to 4.500) compared to non-smokers. A posterior location of the augmentation was associated with lower probability of a wound dehiscence (odds ratio 0.188; P = 0.076; 95% CI: 0.035 to 0.802) compared to an anterior location., Conclusions: Based on this study population, smoking in males seems to be the most important risk factor for the development of wound dehiscences after pre-implant alveolar bone augmentation procedures., Competing Interests: Conflict of interest statement: The authors report no proprietary or commercial interest in any product mentioned or concept discussed in this article. This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.

Background: The most tedious and time-consuming task in medical additive manufacturing (AM) is image segmentation. The aim of the present study was to develop and train a convolutional neural network (CNN) for bone segmentation in computed tomography (CT) scans., Method: The CNN was trained with CT scans acquired using six different scanners. Standard tessellation language (STL) models of 20 patients who had previously undergone craniotomy and cranioplasty using additively manufactured skull implants served as "gold standard" models during CNN training. The CNN segmented all patient CT scans using a leave-2-out scheme. All segmented CT scans were converted into STL models and geometrically compared with the gold standard STL models., Results: The CT scans segmented using the CNN demonstrated a large overlap with the gold standard segmentation and resulted in a mean Dice similarity coefficient of 0.92 ± 0.04. The CNN-based STL models demonstrated mean surface deviations ranging between -0.19 mm ± 0.86 mm and 1.22 mm ± 1.75 mm, when compared to the gold standard STL models. No major differences were observed between the mean deviations of the CNN-based STL models acquired using six different CT scanners., Conclusions: The fully-automated CNN was able to accurately segment the skull. CNNs thus offer the opportunity of removing the current prohibitive barriers of time and effort during CT image segmentation, making patient-specific AM constructs more accesible., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Antibiotic resistance is a challenge in the management of infectious diseases and can cause substantial cost. Even without the onset of infection, measures must be taken, as patients colonized with multi-drug resistant (MDR) pathogens may transmit the pathogen. We aim to quantify the cost of community-acquired MDR colonizations using routine data from a German teaching hospital., Methods: All 2006 cases of documented MDR colonization at hospital admission recorded from 2011 to 2014 are matched to 7917 unexposed controls with the same primary diagnosis. Cases with an onset MDR infection are excluded from the analysis. Routine data on costs per case is analysed for three groups of MDR bacteria: Methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococcus (VRE), and multidrug-resistant gram-negative bacteria (MDR-GN). Multivariate analyses are conducted to adjust for potential confounders., Results: After controlling for main diagnosis group, age, sex, and Charlson Comorbidity Index, MDR colonization is associated with substantial additional costs from the healthcare perspective (€1480.9, 95%CI €1286.4-€1675.5). Heterogeneity between pathogens remains. Colonization with MDR-GN leads to the largest cost increase (€1966.0, 95%CI €1634.6-€2297.4), followed by MRSA with €1651.3 (95%CI €1279.1-€2023.6), and VRE with €879.2 (95%CI €604.1-€1154.2). At the same time, MDR-GN is associated with additional reimbursements of €887.8 (95%CI €722.1-€1053.6), i.e. costs associated with MDR-colonization exceed reimbursement., Conclusions: Even without the onset of invasive infection, documented MDR-colonization at hospital admission is associated with increased hospital costs, which are not fully covered within the German DRG-based hospital payment system.

Competing Interests: The study was approved by the regional Medical Ethics Committee of Noord-Holland, the Netherlands (M016-004). In light of the Declaration of Helsinki, all patients gave oral informed consent to start the intervention. Additional written informed consent was obtained from patients whose photographs were used for publication.Consent for publication was obtained from patients whose photographs have been used in this study.The authors declare that they have no competing interests.

Osseointegration is paramount for the longevity of dental implants and is significantly influenced by biomechanical stimuli. The aim of the present study was to assess the micro-strain and displacement induced by loaded dental implants at different stages of osseointegration using finite element analysis (FEA). Computational models of two mandible segments with different trabecular densities were constructed using microCT data. Three different implant loading directions and two osseointegration stages were considered in the stress-strain analysis of the bone-implant assembly. The bony segments were analyzed using two approaches. The first approach was based on Mechanostat strain intervals and the second approach was based on tensile/compression yield strains. The results of this study revealed that bone surrounding dental implants is critically strained in cases when only a partial osseointegration is present and when an implant is loaded by buccolingual forces. In such cases, implants also encounter high stresses. Displacements of partially-osseointegrated implant are significantly larger than those of fully-osseointegrated implants. It can be concluded that the partial osseointegration is a potential risk in terms of implant longevity., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The objective of the present study was to assess and compare the effective doses in the wrist region resulting from conventional radiography device, multislice computed tomography (MSCT) device and two cone beam computed tomography (CBCT) devices using MOSFET dosemeters and a custom made anthropomorphic RANDO phantom according to the ICRP 103 recommendation. The effective dose for the conventional radiography was 1.0 μSv. The effective doses for the NewTom 5 G CBCT ranged between 0.7 μSv and 1.6 μSv, for the Planmed Verity CBCT 2.4 μSv and for the MSCT 8.6 μSv. When compared with the effective dose for AP- and LAT projections of a conventional radiographic device, this study showed an 8.6-fold effective dose for standard MSCT protocol and between 0.7 and 2.4-fold effective dose for standard CBCT protocols. When compared to the MSCT device, the CBCT devices offer a 3D view of the wrist at significantly lower effective doses.

Objectives: The aim of this study was to assess the interaction of a bioactive glass scaffold with cells derived from dental pulp, dental follicle and periodontal ligament., Material and Methods: Impacted third molars were surgically removed from three young donors. Cells from the dental pulp, follicle and periodontal ligament tissues were isolated and expanded. Different cell populations were characterised using specific CD markers. Expanded pulp, follicle and periodontal cells were then seeded onto bioactive glass scaffolds and cultured in osteogenic medium or basic medium. Cell attachment, viability, proliferation and alkaline phosphatase activity were assessed., Results: This study revealed good biocompatibility of the specific bioactive glass configuration tested and the osteogenic induction of cells derived from dental pulp, dental follicle and periodontal ligament. Osteogenic medium seemed to increase the differentiation pattern and dental pulp stem cells showed the most positive results compared to periodontal ligament and dental follicle stem cells., Conclusions: Dental pulp stem cells combined with a bioactive glass scaffold and exposed to osteogenic medium in vitro represent a promising combination for future study of hard tissue regeneration in the cranio-maxillofacial skeleton.

Background: Psychiatric comorbidities are relevant for the diagnostic and therapeutic regimes in somatic hospital care. The main aim of this study was to analyse the association between psychiatric comorbidities and hospital costs per inpatient episode. A further aim was to discuss and address the methodological challenges in the estimation of these outcomes based on retrospective data., Methods: The study included 338,162 inpatient episodes consecutively discharged between 2011 and 2014 at a German university hospital. We used detailed resource use data to calculate day-specific hospital costs. We adjusted analyses for sex, age, somatic comorbidities and main diagnoses. We addressed potential time-related bias in retrospective diagnosis data with sensitivity analyses., Results: Psychiatric comorbidities were associated with an increase in hospital costs per episode of 40% and an increase of reimbursement per episode of 28%, representing marginal effects of 1344 € and 1004 €, respectively. After controlling for length of stay, sensitivity analyses provided a lower bound increase in daily costs and reimbursement of 207 € and 151 €, respectively., Conclusion: If differences in hospital costs between patient groups are not adequately accounted for in DRG-systems, perverse incentives are created that can reduce the efficiency of care. Therefore, we suggest intensifying the inclusion of psychiatric comorbidities in the German DRG system. Future research should investigate the appropriate inclusion of psychiatric comorbidities in other health care systems' payment schemes.

Objective: To assess the accuracy of five different computed tomography (CT) scanners for the evaluation of the oropharynx morphology., Methods: An existing cone-beam computed tomography (CBCT) data set was used to fabricate an anthropomorphic phantom of the upper airway volume that extended from the uvula to the epiglottis (oropharynx) with known dimensions (gold standard). This phantom was scanned using two multi-detector row computed tomography (MDCT) scanners (GE Discovery CT750 HD, Siemens Somatom Sensation) and three CBCT scanners (NewTom 5G, 3D Accuitomo 170, Vatech PaX Zenith 3D). All CT images were segmented by two observers and converted into standard tessellation language (STL) models. The volume and the cross-sectional area of the oropharynx were measured on the acquired STL models. Finally, all STL models were registered and compared with the gold standard., Results: The intra- and inter-observer reliability of the oropharynx segmentation was fair to excellent. The most accurate volume measurements were acquired using the Siemens MDCT (98.4%; 14.3 cm3) and Vatech CBCT (98.9%; 14.4 cm3) scanners. The GE MDCT, NewTom 5G CBCT, and Accuitomo CBCT scanners resulted in smaller volumes, viz., 92.1% (13.4 cm3), 91.5% (13.3 cm3), and 94.6% (13.8 cm3), respectively. The most accurate cross-sectional area measurements were acquired using the Siemens MDCT (94.6%; 282.4 mm2), Accuitomo CBCT (95.1%; 283.8 mm2), and Vatech CBCT (95.3%; 284.5 mm2) scanners. The GE MDCT and NewTom 5G CBCT scanners resulted in smaller areas, viz., 89.3% (266.5 mm2) and 89.8% (268.0 mm2), respectively., Limitations: Images of the phantom were acquired using the vendor-supplied default airway scanning protocol for each scanner., Conclusion: Significant differences were observed in the volume and cross-sectional area measurements of the oropharynx acquired using different MDCT and CBCT scanners. The Siemens MDCT and the Vatech CBCT scanners were more accurate than the GE MDCT, NewTom 5G, and Accuitomo CBCT scanners. In clinical settings, CBCT scanners offer an alternative to MDCT scanners in the assessment of the oropharynx morphology., (© The Author 2017. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com)

Purpose: Imaging phantoms are widely used for testing and optimization of imaging devices without the need to expose humans to irradiation. However, commercially available phantoms are commonly manufactured in simple, generic forms and sizes and therefore do not resemble the clinical situation for many patients., Methods: Using 3D printing techniques, we created a life-size phantom based on a clinical CT scan of the thorax from a patient with lung cancer. It was assembled from bony structures printed in gypsum, lung structures consisting of airways, blood vessels >1 mm, and outer lung surface, three lung tumors printed in nylon, and soft tissues represented by silicone (poured into a 3D-printed mold)., Results: Kilovoltage x-ray and CT images of the phantom closely resemble those of the real patient in terms of size, shapes, and structures. Surface comparison using 3D models obtained from the phantom and the 3D models used for printing showed mean differences <1 mm for all structures. Tensile tests of the materials used for the phantom show that the phantom is able to endure radiation doses over 24,000 Gy., Conclusions: It is feasible to create an anthropomorphic thorax phantom using 3D printing and molding techniques. The phantom closely resembles a real patient in terms of spatial accuracy and is currently being used to evaluate x-ray-based imaging quality and positional verification techniques for radiotherapy., (© 2017 American Association of Physicists in Medicine.)

Aim of the Study: The accuracy of additive manufactured medical constructs is limited by errors introduced during image segmentation. The aim of this study was to review the existing literature on different image segmentation methods used in medical additive manufacturing., Methods: Thirty-two publications that reported on the accuracy of bone segmentation based on computed tomography images were identified using PubMed, ScienceDirect, Scopus, and Google Scholar. The advantages and disadvantages of the different segmentation methods used in these studies were evaluated and reported accuracies were compared., Results: The spread between the reported accuracies was large (0.04 mm - 1.9 mm). Global thresholding was the most commonly used segmentation method with accuracies under 0.6 mm. The disadvantage of this method is the extensive manual post-processing required. Advanced thresholding methods could improve the accuracy to under 0.38 mm. However, such methods are currently not included in commercial software packages. Statistical shape model methods resulted in accuracies from 0.25 mm to 1.9 mm but are only suitable for anatomical structures with moderate anatomical variations., Conclusions: Thresholding remains the most widely used segmentation method in medical additive manufacturing. To improve the accuracy and reduce the costs of patient-specific additive manufactured constructs, more advanced segmentation methods are required., (Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.)

Objectives: In the Netherlands, cyclists continue to outnumber other road users in injuries and deaths. The wearing of bicycle helmets is not mandatory in the Netherlands even though research has shown that wearing bicycle helmets can reduce head and brain injuries by up to 88%. Therefore, the aim of this study was to assess the feasibility of using 3D technology to evaluate bicycle-related head injuries and helmet protection., Methods: Three patients who had been involved in a bicycle accident while wearing a helmet were subjected to multi-detector row computed tomography (MDCT) imaging after trauma. The helmets were separately scanned using the same MDCT scanner with tube voltages ranging from 80kVp to 140kVp and tube currents ranging from 10mAs to 300mAs in order to determine the best image acquisition parameters for helmets. The acquired helmet images were converted into virtual 3D surface hence Standard Tessellation Language (STL) models and merged with MDCT-derived STL models of the patients' skulls. Finally, all skull fractures and corresponding helmet damage were visualized and related., Results: Imaging bicycle helmets on an MDCT scanner proved to be feasible using a tube voltage of 120kVp and a tube current of 120mAs. Merging the resulting STL models of the patients' skull and helmet allowed the overall damage sustained by both skull and helmet to be related., Conclusion: Our proposed 3D method of assessing bicycle helmet damage and corresponding head injuries could offer valuable information for the development and design of safer bicycle helmets., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: The effective utilization of staff resources is of decisive importance for the adequate, appropriate, and economical delivery of hospital services. The goal of this study was to determine the distribution of working time among doctors in a German university hospital-in particular, in terms of type of activities and time of day., Methods: The distribution of working time was determined from 14-day samples taken in seven clinical departments of the Medical Center-University of Freiburg. In each 14-day sample, the activities being carried out at multiple, randomly chosen times were recorded., Results: A total of 250 doctors (participation rate: 83%) took part in the study. A total of 20 715 hours of working time was analyzed, representing twelve years of full-time employment. Overall, 46% of working time in the inpatient sector was spent in direct contact with patients, with relevant differences among the participating clinical departments: for instance, the percentage of time taken up by patient contact was 35% in pediatrics and 60% in oral and maxillofacial surgery. Patient contact was highest (over 50% overall) in the period 8 a.m. to 12 noon., Conclusion: The amount of working time taken up by activities other than direct patient contact was found to be lower than in previous studies. It remains unclear what distribution of working time is best for patient care and whether it would be possible or desirable to increase the time that doctors spend in direct contact with patients.