Robot-assisted surgery and artificial intelligence-based tumour diagnostics: social preferences with a representative cross-sectional survey.

BACKGROUND: The aim of this study was to assess social preferences for two different advanced digital health technologies and investigate the contextual dependency of the preferences. METHODS: A cross-sectional online survey was performed among the general population of Hungary aged 40 years and over. Participants were asked to imagine that they needed a total hip replacement surgery and to indicate whether they would prefer a traditional or a robot-assisted (RA) hip surgery. To better understand preferences for the chosen method, the willingness to pay (WTP) method was used. The same assessment was conducted for preferences between a radiologist's and AI-based image analysis in establishing the radiological diagnosis of a suspected tumour. Respondents' electronic health literacy was assessed with the eHEALS questionnaire. Descriptive methods were used to assess sample characteristics and differences between subgroups. Associations were investigated with correlation analysis and multiple linear regressions. RESULTS: Altogether, 1400 individuals (53.7% female) with a mean age of 58.3 (SD = 11.1) years filled in the survey. RA hip surgery was chosen by 762 (54.4%) respondents, but only 470 (33.6%) chose AI-based medical image evaluation. Those who opted for the digital technology had significantly higher educational levels and electronic health literacy (eHEALS). The majority of respondents were willing to pay to secure their preferred surgical (surgeon 67.2%, robot-assisted: 68.8%) and image assessment (radiologist: 70.9%; AI: 77.4%) methods, reporting similar average amounts in the first (p = 0.677), and a significantly higher average amount for radiologist vs. AI in the second task (p = 0.001). The regression showed a significant association between WTP and income, and in the hip surgery task, it also revealed an association with the type of intervention chosen. CONCLUSIONS: Individuals with higher education levels seem to accept the advanced digital medical technologies more. However, the greater openness for RA surgery than for AI image assessment highlights that social preferences may depend considerably on the medical situation and the type of advanced digital technology. WTP results suggest rather firm preferences in the great majority of the cases. Determinants of preferences and real-world choices of affected patients should be further investigated in future studies.

Epidemiology and patients' self-reported knowledge of implantable medical devices: Results of a cross-sectional survey in Hungary.

BACKGROUND: Implantable medical devices (IMDs) are medical instruments embedded inside the body. Well-informed and empowered patients living with IMDs are key players of improving IMD-related patient safety and health outcomes. However, little is known about IMD patients' epidemiology, characteristics, and current awareness levels. Our primary aim was to investigate the point and lifetime prevalence of patients living with IMDs. Patients' IMD-related knowledge and determinants of IMDs' impact on their life were also explored. METHODS: An online cross-sectional survey was conducted. Respondents' IMD history, whether they received instructions for use and IMD's overall impact on life were recorded by self-reports. Patients' knowledge about living with IMDs was assessed on visual analogue scales (VAS, 0-10). Shared decision-making was analyzed by the 9-item Shared Decision Making Questionnaire (SDM-Q-9). Descriptive statistics and subgroup comparisons between IMD wearers were performed for statistical differences. Significant determinants of IMD's overall impact on life were examined in linear regression analysis. RESULTS: In the total sample (N = 1400, mean age 58.1 ±11.1; female 53.7%), nearly one third of respondents were living with IMD (30.9%; 433/1400). Among them, the most frequent IMDs were tooth implants (30.9%) and intraocular lens (26.8%). Mean knowledge VAS scores were similar (range: 5.5 ±3.8-6.5 ±3.2) but differences by IMD types were observed. Patients who received instructions for use or reported better impact on life indicated higher self-reported knowledge. Regression confirmed that patients' knowledge was significant predictor of IMD's impact on life, but this effect was overwritten by the SDM-Q-9. CONCLUSIONS: This first comprehensive epidemiological study on IMDs provides basic data for public health strategy planning alongside the implementation of MDR. Improved self-perceived outcomes were associated with higher knowledge hence education of patients receiving IMD deserves consideration. We suggest to investigate further the role of shared decision-making on IMD's overall impact on patients' life in future prospective studies.

Enhancement of Hydrophilicity of Nano-Pitted TiO2 Surface Using Phosphoric Acid Etching.

Our research group developed a novel nano-pitted (NP) TiO2 surface on grade 2 titanium that showed good mechanical, osteogenic, and antibacterial properties; however, it showed weak hydrophilicity. Our objective was to develop a surface treatment method to enhance the hydrophilicity of the NP TiO2 surface without the destruction of the nano-topography. The effects of dilute and concentrated orthophosphoric (H3PO4) and nitric acids were investigated on wettability using contact angle measurement. Optical profilometry and atomic force microscopy were used for surface roughness measurement. The chemical composition of the TiO2 surface and the oxidation state of Ti was investigated using X-ray photoelectron spectroscopy. The ccH3PO4 treatment significantly increased the wettability of the NP TiO2 surfaces (30°) compared to the untreated control (88°). The quantity of the absorbed phosphorus significantly increased following ccH3PO4 treatment compared to the control and caused the oxidation state of titanium to decrease (Ti4+ → Ti3+). Owing to its simplicity and robustness the presented surface treatment method may be utilized in the industrial-scale manufacturing of titanium implants.

Is the trend of increasing use of patient-reported outcome measures in medical device studies the sign of shift towards value-based purchasing in Europe?

BACKGROUND: The recent update of the European Union's (EU) regulation on public procurement has created new opportunity for progress in the purchasing of medical devices by shifting towards focus on value from one purely on price. Patient-reported outcome measures (PROMs) may serve as additional tools for manufacturers to demonstrate value beyond traditional metrics of safety and performance and to differentiate their products in a market of increasing competition. The aim of our study was to investigate the extent to which PROMs are included in registered device studies in the EU and interpret the results in the context of the purchasing of medical devices. METHODS: Twelve device groups were searched in clinical trial registries to determine the frequency distribution of PROMs in related studies. RESULTS: Results indicate that clinical studies of the selected device categories are done predominately in the western EU nations and are increasingly including PROMs. In the United Kingdom 121 (65%) study, out of 186 included PROMs, and in Germany, 92 (52%) out of 178 between 1998 and 2018. Few device studies were done in the Central and Eastern European region, and out of 76 studies 27 (35%) included PROMs. Since there is no requirement to include PROMs in device studies for regulatory purposes, it seems probable that their increasing use is driven by competitive market pressures. CONCLUSION: The trend of increasing use of PROMs might be driven by the demand of purchasers to demonstrate value of devices, but is manifested at different levels in various regions of the EU.

Validity and reliability of the 9-item Shared Decision Making Questionnaire (SDM-Q-9) in a national survey in Hungary.

BACKGROUND: The nine-item Shared Decision Making Questionnaire (SDM-Q-9) is one of the most frequently applied instruments for assessing patients' involvement in medical decision-making. Our objectives were to develop a Hungarian version of SDM-Q-9, to evaluate its psychometric properties and to compare its performance between primary and specialised care settings. METHODS: In 2019, a sample of adults (n = 537) representative of the Hungarian general population in terms of age, gender and geographic region completed an online survey with respect to a recent health-related decision. Outcome measures included SDM-Q-9 and Control Preferences Scale-post (CPSpost). Item characteristics, internal consistency reliability and the factor structure of SDM-Q-9 were determined. RESULTS: The overall ceiling and floor effects for SDM-Q-9 total scores were 12.3% and 2.2%, respectively. An excellent internal consistency reliability (Cronbach's alpha 0.925) was demonstrated. Exploratory factor analysis resulted in a one-factor model explaining 63.5% of the variance of SDM-Q-9. A confirmatory factor analysis supported the acceptability of this model. Known-groups validity was confirmed with CPSpost categories; mean SDM-Q-9 total scores were higher in the 'Shared decision' category (72.6) compared to both 'Physician decided' (55.1, p = 0.0002) and 'Patient decided' (57.2, p = 0.0086) categories. In most aspects of validity and reliability, there was no statistically significant difference between primary and specialised care. CONCLUSIONS: The overall good measurement properties of the Hungarian SDM-Q-9 make the questionnaire suitable for use in both primary and specialised care settings. SDM-Q-9 may be useful for health policies targeting the implementation of shared decision-making and aiming to improve efficiency and quality of care in Hungary.

Novel radiomics evaluation of bone formation utilizing multimodal (SPECT/X-ray CT) in vivo imaging.

Although an extensive research is being undertaken, the ideal bone graft and evaluation method of the bone formation draw still a warranted attention. The purpose of this study was to develop a novel multimodal radiomics evaluation method, utilizing X-ray computed tomography (CT) and single photon emission computed tomography (SPECT) with Tc-99m-Methyl diphosphonate (Tc-99m-MDP) tracer. These modalities are intended to provide quantitative data concerning the mineral bone density (after evaluation it is referred to as opacity) and the osteoblast activity, at the same time. The properties of bone formation process within poly (methyl methacrylate)-based bone cement graft (PMMA) was compared to that of albumin coated, sterilized, antigen-extracted freeze-dried human bone grafts (HLBC), in caudal vertebrae (C5) of rats. The animals were scanned at 3 and 8 weeks after surgery. In both groups, the mean opacity increased, while the mean Tc-99m-MDP activity decreased. The later parameter was significant (n = 4, p = 0.002) only in HLBC group. The linear regression analysis of PMMA-treated group variables (mean opacity increase; mean Tc-99m-MDP activity decrease), revealed a negative correlation with the medium strength (r = 0.395, p = 0.605). Whereas, it showed strong positive correlation when HLBC group variables were analyzed (r = 0.772, p = 0.012). These results indicate that using HLBC grafts is advantageous in terms of the osteoblast activity and bone vascularization over PMMA cement. Using this regression analysis method, we were able to distinguish characteristics that otherwise could not be distinguished by a regular data analysis. Hence, we propose utilizing this novel method in preclinical tests, and in clinical monitoring of bone healing, in order to improve diagnosis of bone-related diseases.

Osteogenic nanostructured titanium surfaces with antibacterial properties under conditions that mimic the dynamic situation in the oral cavity.

The study aim was to assess the impact of different surface nanofeatures on otherwise smooth titanium surfaces on bacterial adhesion as well as on their osteogenic potential. Bacterial adhesion was assessed in the presence of saliva under static and dynamic conditions to approximate both sub- and supragingival conditions in the oral cavity as the gingival seal will be affected by implantation. The ultimate goal was to develop a surface that will reduce biofilm formation but still support osseointegration in vivo. To this end nanotubular or nanopitted surfaces were created on electropolished titanium via electrochemical anodization procedures. Sandblasted/acid etched surfaces (SBAE) were used as a microrough reference. Bacterial adhesion was studied using saliva-precoated samples with S. sanguinis as a typical early colonizer of the oral cavity; osteogenic differentiation was assessed with human bone marrow stromal cells. While bacterial adhesion was reduced on all microsmooth surfaces to an average of 17% surface coverage compared to 61% on SBAE under static conditions, under dynamic conditions the nanopitted surface had a significant impact on bacterial adhesion. Here fluid flow removed all bacteria. By comparison, the reduction on the nanotubular surface was only similar to that of the SBAE reference. We hypothesise the underlying cause to be an effect of the surface morphology on the structure and composition of the saliva precoating that reduces its stability, giving rise to a self-cleaning effect. In addition, no negative influence on the osteogenic potential of the nanopitted surface could be determined by alkaline phosphatase activity, mineralization behaviour or gene expression; it remained on a par with the tissue culture plastic control. Thus, nanopitting seems to be a promising surface treatment candidate for dental implants to reduce infection related complications without compromising the implant integration.

Review: the potential impact of surface crystalline states of titanium for biomedical applications.

In many biomedical applications, titanium forms an interface with tissues, which is crucial to ensure its long-term stability and safety. In order to exert control over this process, titanium implants have been treated with various methods that induce physicochemical changes at nano and microscales. In the past 20 years, most of the studies have been conducted to see the effect of topographical and physicochemical changes of titanium surface after surface treatments on cells behavior and bacteria adhesion. In this review, we will first briefly present some of these surface treatments either chemical or physical and we explain the biological responses to titanium with a specific focus on adverse immune reactions. More recently, a new trend has emerged in titanium surface science with a focus on the crystalline phase of titanium dioxide and the associated biological responses. In these recent studies, rutile and anatase are the major two polymorphs used for biomedical applications. In the second part of this review, we consider this emerging topic of the control of the crystalline phase of titanium and discuss its potential biological impacts. More in-depth analysis of treatment-related surface crystalline changes can significantly improve the control over titanium/host tissue interface and can result in considerable decreases in implant-related complications, which is currently a big burden on the healthcare system.

Investigation of the mechanical and chemical characteristics of nanotubular and nano-pitted anodic films on grade 2 titanium dental implant materials.

OBJECTIVE: The objective of this study was to investigate the reproducibility, mechanical integrity, surface characteristics and corrosion behavior of nanotubular (NT) titanium oxide arrays in comparison with a novel nano-pitted (NP) anodic film. METHODS: Surface treatment processes were developed to grow homogenous NT and NP anodic films on the surface of grade 2 titanium discs and dental implants. The effect of process parameters on the surface characteristics and reproducibility of the anodic films was investigated and optimized. The mechanical integrity of the NT and NP anodic films were investigated by scanning electron microscopy, surface roughness measurement, scratch resistance and screwing tests, while the chemical and physicochemical properties were investigated in corrosion tests, contact angle measurement and X-ray photoelectron spectroscopy (XPS). RESULTS AND DISCUSSION: The growth of NT anodic films was highly affected by process parameters, especially by temperature, and they were apt to corrosion and exfoliation. In contrast, the anodic growth of NP film showed high reproducibility even on the surface of 3-dimensional screw dental implants and they did not show signs of corrosion and exfoliation. The underlying reason of the difference in the tendency for exfoliation of the NT and NP anodic films is unclear; however the XPS analysis revealed fluorine dopants in a magnitude larger concentration on NT anodic film than on NP surface, which was identified as a possible causative. Concerning other surface characteristics that are supposed to affect the biological behavior of titanium implants, surface roughness values were found to be similar, whereas considerable differences were revealed in the wettability of the NT and NP anodic films. CONCLUSION: Our findings suggest that the applicability of NT anodic films on the surface of titanium bone implants may be limited because of mechanical considerations. In contrast, it is worth to consider the applicability of nano-pitted anodic films over nanotubular arrays for the enhancement of the biological properties of titanium implants.

Osteogenic potential of Sr-doped calcium phosphate hollow spheres in vitro and in vivo.

Treatment of osteoporotic fractures with conventional surgical methods is associated with a high rate of complications. Intense search for new treatment options includes development of specific biomaterials aimed to be part of the surgical armamentarium. Strontium doped calcium phosphate spheres (SrCPS) is a new material that might be of interest due to the influence on osteoclast and osteoblast activity. In the present study, we successfully constructed hollow spherical SrCPS particles with a diameter of ~700 nm and shell thickness of ~150 nm. The Sr content was about 20 wt %. Cell viability and cytotoxicity were investigated in vitro with concentrations from 0 to 1000 µg/mL of SrCPS in medium extract in a day chase study. The in vivo biocompatibility was tested in a delayed bone-healing model in a rat vertebral defect by histology, µCT, and nanoSPECT. The SrCPS showed no toxicity in vitro with comparable cell number in all concentrations. Increased metabolism was seen in the cell viability study in cells exposed to 400 and 600 µg/mL. SPECT showed good biocompatibility with no local adverse effects and an increased osteoblast activity as compared to adjacent vertebra. SrCPS implantation induced bone formation and resulted in complete resorption and defect consolidation.

Serum albumin enhances bone healing in a nonunion femoral defect model in rats: a computer tomography micromorphometry study.

PURPOSE: Blood-derived proliferative factors such as platelet rich plasma or activated plasma are promising adjuvants for bone grafts. Our earlier studies showed that serum albumin itself can markedly enhance the proliferation of stem cells on bone allograft and postulated that albumin coating alone may improve bone graft integration in vivo. METHODS: Two femoral defect models were performed in adult male Wistar rats. In the critical size model a six millimetre gap was created in the midshaft of the femur and fixed with plate and screws, while a nonunion model was established by the interposition of a spacer in the osteotomy for four weeks which resulted in compromised healing and nonunion. Albumin coated and uncoated grafts were placed into the defects. Bone healing and morphometry were evaluated by µCT and histology four weeks after implantation of the grafts. RESULTS: In the critical size model none of the bone grafts were able to bridge the defect, and graft resorption was the typical outcome. In the nonunion model regular uncoated grafts had a low union rate (two out of six), which increased markedly when albumin coating was applied (six out of eight). Trabecular thickness and pattern factor improved significantly in the albumin coated group versus uncoated or empty controls. CONCLUSIONS: Our results showed that serum albumin coating of bone grafts can enhance the remodelling and efficacy of treatment in a nonunion model.

Albumin-coated bioactive suture for cell transplantation.

Cell therapy holds the promise for a novel modality in the surgical toolkit; however, delivery of cells into damaged soft tissues constitutes a challenge. The authors hypothesized that growing stem cells on the surface of absorbable sutures in vitro and then implanting them via stitching would be a suitable delivery route for cell therapy. Fibronectin, poly-L-lysine, and albumin coatings were used to increase attachment of human and rat bone-marrow-derived mesenchymal stem cells (BMSC) to polyfilament absorbable sutures in vitro. Fluorescence microscopy was performed to localize the cells on the suture. After 48 hours of incubation, the albumin-coated sutures had the highest cell number, and after 168 hours cell number reached confluency. In the in vivo experiments, a 10-mm incision was made on the triceps surae muscle of male Wistar rats and rat BMSC coated sutures were placed into the muscle. Two days after the implantation, cells were seen on the surface of the sutures as well as in the surrounding muscle tissue. Long-term results at 5 weeks showed that transplanted cells survived and the sutures were partly absorbed. In conclusion, coating absorbable sutures with proteins, especially serum albumin, improves attachment and proliferation of cells, and only 48 hours in culture is enough to cover the sutures sufficiently. Using these stitches in vivo resulted in short-term and long-term survival of cells. As a result, albumin-coated suture can be a vehicle for stem cell therapy in soft tissues such as muscle, tendon, or peripheral nerves.

Freeze-dried human serum albumin improves the adherence and proliferation of mesenchymal stem cells on mineralized human bone allografts.

Mineralized scaffolds are widely used as bone grafts with the assumption that bone marrow derived cells colonize and remodel them. This process is slow and often unreliable so we aimed to improve the biocompatibility of bone grafts by pre-seeding them with human mesenchymal stem cells from either bone marrow or dental pulp. Under standard cell culture conditions very low number of seeded cells remained on the surface of freeze-dried human or bovine bone graft or hydroxyapatite. Coating the scaffolds with fibronectin or collagen improved seeding efficiency but the cells failed to grow on the surface until the 18th day. In contrast, human albumin was a very potent facilitator of both seeding and proliferation on allografts which was further improved by culturing in a rotating bioreactor. Electron microscopy revealed that cells do not form a monolayer but span the pores, emphasizing the importance of pore size and microstructure. Albumin coated bone chips were able to unite a rat femoral segmental defect, while uncoated ones did not. Micro-hardness measurements confirmed that albumin coating does not influence the physical characteristics of the scaffold, so it is possible to introduce albumin coating into the manufacturing process of lyophilized bone allografts.

In vivo evaluation of an injectable premixed radiopaque calcium phosphate cement.

In this work a radiopaque premixed calcium phosphate cement (pCPC) has been developed and evaluated in vivo. Radiopacity was obtained by adding 0-40 % zirconia to the cement paste. The effects of zirconia on setting time, strength and radiopacity were evaluated. In the in vivo study a 2 by 3.5 mm cylindrical defect in a rat vertebrae was filled with either the pCPC, PMMA or bone chips. Nano-SPECT CT analysis was used to monitor osteoblast activity during bone regeneration. The study showed that by adding zirconia to the cement the setting time becomes longer and the compressive strength is reduced. All materials evaluated in the in vivo study filled the bone defect and there was a strong osteoblast activity at the injury site. In spite of the osteoblast activity, PMMA blocked bone healing and the bone chips group showed minimal new bone formation. At 12 weeks the pCPC was partially resorbed and replaced by new bone with good bone ingrowth. The radiopaque pCPC may be considered to be used for minimal invasive treatment of vertebral fractures since it has good handling, radiopacity and allows healing of cancellous bone in parallel with the resorption of the cement.