Phase-Specific Healthcare Costs Associated With Giant Cell Arteritis in Ontario, Canada.

OBJECTIVE: To estimate the additional healthcare system costs associated with giant cell arteritis (GCA) in the 1-year prediagnosis and postdiagnosis periods and over long-term follow-up compared to individuals with similar demographics and comorbidities without GCA. METHODS: We performed a population-based study using health administrative data. Newly diagnosed cases of GCA (between 2002 and 2017 and aged ≥ 66 years) were identified using a validated algorithm and matched 1:6 to comparators using propensity scores. Follow-up data were accrued until death, outmigration, or March 31, 2020. The costs associated with care were determined across 3 phases: the year before the diagnosis of GCA, the year after, and ongoing costs thereafter in 2021 Canadian dollars (CAD). RESULTS: The cohort consisted of 6730 cases of GCA and 40,380 matched non-GCA comparators. The average age was 77 (IQR 72-82) years and 68.2% were female. A diagnosis of GCA was associated with an increased cost of CAD $6619.4 (95% CI 5964.9-7274.0) per patient during the 1-year prediagnostic period, $12,150.3 (95% CI 11,233.1-13,067.6) per patient in the 1-year postdiagnostic phase, and $20,886.2 (95% CI 17,195.2-24,577.2) per patient during ongoing care for year 3 onward. Increased costs were driven by inpatient hospitalizations, physician services, hospital outpatient clinic services, and emergency department visits. CONCLUSION: A diagnosis of GCA was associated with increased healthcare costs during all 3 phases of care. Given the substantial economic burden, strategies to reduce the healthcare utilization and costs associated with GCA are warranted.

Sustainable Bombyx mori's silk fibroin for biomedical applications as a molecular biotechnology challenge: A review.

Silk is a natural engineering material with a unique set of properties. The major constituent of silk is fibroin, a protein widely used in the biomedical field because of its mechanical strength, toughness and elasticity, as well as its biocompatibility and biodegradability. The domestication of silkworms allows large amounts of fibroin to be extracted inexpensively from silk cocoons. However, the industrial extraction process has drawbacks in terms of sustainability and the quality of the final medical product. The heterologous production of fibroin using recombinant DNA technology is a promising approach to address these issues, but the production of such recombinant proteins is challenging and further optimization is required due to the large size and repetitive structure of fibroin's DNA and amino acid sequence. In this review, we describe the structure-function relationship of fibroin, the current extraction process, and some insights into the sustainability of silk production for biomedical applications. We focus on recent advances in molecular biotechnology underpinning the production of recombinant fibroin, working toward a standardized, successful and sustainable process.

Combined severe plastic deformation processing of commercial purity titanium enables superior fatigue resistance for next generation implants.

Commercial purity titanium (cp-Ti) is considered for replacing Ti64 as an implant material in various applications, due to the potential toxicity associated with the release of Al and V ions. However, the mechanical properties of cp-Ti, particularly fatigue resistance, are inadequate for this purpose. In this study, cp-Ti grade 4 rods were processed using a combination of equal channel angular pressing and rotary swaging (ECAP/RS). Tensile and fatigue tests were conducted, along with detailed microscopy and evaluation of corrosion resistance and biocompatibility. An average yield strength of 1383 MPa was obtained while maintaining moderate ductility of 10 %. This represents the highest strength ever recorded for cp-Ti, even exceeding that of Ti64. Additionally, fatigue endurance limit increased by 43 % up to 600 MPa, almost obtaining that of Ti64. Strengthening mechanisms were attributed to the ultrafine-grained (UFG) microstructure generated by ECAP/RS, along with strong crystallographic texture and formation of sub-grain structure. Furthermore, the corrosion resistance and biocompatibility of cp-Ti were largely unaffected, potentially easing regulatory transition in future medical devices. Thus, these results demonstrate high potential of combined ECAP/RS processing to manufacture UFG cp-Ti grade 4 materials that prospectively allow for the substitution of questionable alloys and downsizing of medical implants.

Layer-by-Layer Deposition of Regenerated Silk Fibroin─An Approach to the Surface Coating of Biomedical Implant Materials.

Biomaterials and coating techniques unlock major benefits for advanced medical therapies. Here, we explored layer-by-layer (LbL) deposition of silk fibroin (SF) by dip coating to deploy homogeneous films on different materials (titanium, magnesium, and polymers) frequently used for orthopedic and other bone-related implants. Titanium and magnesium specimens underwent preceding plasma electrolytic oxidation (PEO) to increase hydrophilicity. This was determined as surface properties were visualized by scanning electron microscopy and contact angle measurements as well as Fourier transform infrared spectroscopy (FTIR) analysis. Finally, biological in vitro evaluations of hemocompatibility, THP-1 cell culture, and TNF-α assays were conducted. A more hydrophilic surface could be achieved using the PEO surface, and the contact angle for magnesium and titanium showed a reduction from 73 to 18° and from 58 to 17°, respectively. Coating with SF proved successful on all three surfaces, and coating thicknesses of up to 5.14 µm (±SD 0.22 µm) were achieved. Using FTIR analysis, it was shown that the insolubility of the material was achieved by post-treatment with water vapor annealing, although the random coil peak (1640-1649 cm-1) and the α-helix peak (at 1650 cm-1) were still evident. SF did not change hemocompatibility, regardless of the substrate, whereas the PEO-coated materials showed improved hemocompatibility. THP-1 cell culture showed that cells adhered excellently to all of the tested material surfaces. Interestingly, SF coatings induced a significantly higher amount of TNF-α for all materials, indicating an inflammatory response, which plays an important role in a variety of physiological processes, including osteogenesis. LbL coatings of SF are shown to be promising candidates to modulate the body's immune response to implants manufactured from titanium, magnesium, and polymers. They may therefore facilitate future applications for bioactive implant coatings. However, further in vivo studies are needed to confirm the proposed effects on osteogenesis in a physiological environment.

Association of maternal risk factors with infant maltreatment: an administrative data cohort study.

OBJECTIVE: We aimed to evaluate the risk of infant maltreatment associated with commonly used criteria for home visiting programmes: young maternal age, maternal adversity (homelessness, substance abuse, intimate partner violence), newcomer status and mental health concerns in Ontario, Canada. DESIGN: This retrospective cohort study included infants born in hospital in Ontario from 1 April 2005 to 31 March 2017 captured in linked health administrative and demographic databases. Infants were followed from newborn hospitalisation until 1 year of age for child maltreatment captured in healthcare or death records. The association between type and number of maternal risk factors, and maltreatment, was analysed using multivariable logistic regression modelling, controlling for infant characteristics and material deprivation. Further modelling explored the association of each year of maternal age with maltreatment. RESULTS: Of 989 586 infants, 434 (0.04%) had recorded maltreatment. Maternal age <22 years conferred higher risk of infant maltreatment (adjusted OR (aOR) 5.5, 95% CI 4.5 to 6.8) compared with age ≥22 years. Maternal mental health diagnoses (aOR 2.0, 95% CI 1.6 to 2.5) were also associated with maltreatment, while refugee status appeared protective (aOR 0.6, 95% CI 0.4 to 1.0). The odds of maltreatment increased with higher numbers of maternal risk factors. Maternal age was associated with maltreatment until age 28 years. CONCLUSION: Infants born to young mothers are at greater risk of infant maltreatment, and this association remained until age 28 years. These findings are important for ensuring public health interventions are supporting populations experiencing structural vulnerabilities with the aim of preventing maltreatment.

Evolution from Bioinert to Bioresorbable: In Vivo Comparative Study of Additively Manufactured Metal Bone Scaffolds.

Additively manufactured scaffolds offer significant potential for treating bone defects, owing to their porous, customizable architecture and functionalization capabilities. Although various biomaterials have been investigated, metals - the most successful orthopedic material - have yet to yield satisfactory results. Conventional bio-inert metals, such as titanium (Ti) and its alloys, are widely used for fixation devices and reconstructive implants, but their non-bioresorbable nature and the mechanical property mismatch with human bones limit their application as porous scaffolds for bone regeneration. Advancements in additive manufacturing have facilitated the use of bioresorbable metals, including magnesium (Mg), zinc (Zn), and their alloys, as porous scaffolds via Laser Powder Bed Fusion (L-PBF) technology. This in vivo study presents a comprehensive, side-by-side comparative analysis of the interactions between bone regeneration and additively manufactured bio-inert/bioresorbable metal scaffolds, as well as their therapeutic outcomes. The research offers an in-depth understanding of the metal scaffold-assisted bone healing process, illustrating that Mg and Zn scaffolds contribute to the bone healing process in distinct ways, but ultimately deliver superior therapeutic outcomes compared to Ti scaffolds. These findings suggest that bioresorbable metal scaffolds hold considerable promise for the clinical treatment of bone defects in the near future.

Bioglues Based on an Elastin-Like Recombinamer: Effect of Tannic Acid as an Additive on Tissue Adhesion and Cytocompatibility.

More than 260 million surgical procedures are performed worldwide each year. Although sutures and staples are widely used to reconnect tissues, they can cause further damage and increase the risk of infection. Bioadhesives have been proposed as an alternative to reconnect tissues. However, clinical adhesives that combine strong adhesion with cytocompatibility have yet to be developed. In this study, we explored the production of adhesives based on protein-engineered polymers bioinspired by the sequence of elastin (i.e., elastin-like recombinamers, ELRs). We hypothesized that the combination of polyphenols (i.e., tannic acid, TA) and ELRs would produce an adhesive coacervate (ELR+TA), as reported for other protein polymers such as silk fibroin (SF). Notably, the adhesion of ELR alone surpassed that of ELR+TA. Indeed, ELR alone achieved adhesive strengths of 88.8 ± 33.2 kPa and 17.0 ± 2.0 kPa on porcine bone and skin tissues, respectively. This surprising result led us to explore a multicomponent bioadhesive to encompass the complementary roles of elastin (mimicked here by ELR) and silk fibroin (SF), and subsequently mirror more closely the multicomponent nature of the extracellular matrix. Tensile testing showed that ELR+SF achieved an adhesive strength of 123.3 ± 60.2 kPa on porcine bone and excellent cytocompatibility. To express this in a more visual and intuitive way, a small surface of only 2.5 cm2 was able to lift at least 2 kg of weight. This opens the door for further studies focusing on the ability of protein-engineered polymers to adhere to biological tissues without further chemical modification for applications in tissue engineering.

Virtual Care and Emergency Department Use During the COVID-19 Pandemic Among Patients of Family Physicians in Ontario, Canada.

Importance: The COVID-19 pandemic has played a role in increased use of virtual care in primary care. However, few studies have examined the association between virtual primary care visits and other health care use. Objective: To evaluate the association between the percentage of virtual visits in primary care and the rate of emergency department (ED) visits. Design, Setting, and Participants: This cross-sectional study used routinely collected administrative data and was conducted in Ontario, Canada. The sample comprised family physicians with at least 1 primary care visit claim between February 1 and October 31, 2021, and permanent Ontario residents who were alive as of March 31, 2021. All residents were assigned to physicians according to enrollment and billing data. Exposure: Family physicians' virtual visit rate was the exposure. Physicians were stratified by the percentage of total visits that they delivered virtually (via telephone or video) during the study period (0% [100% in person], >0%-20%, >20%-40%, >40%-60%, >60%-80%, >80% to <100%, or 100%). Main Outcomes and Measures: Population-level ED visit rate was calculated for each stratum of virtual care use. Multivariable regression models were used to understand the relative rate of patient ED use after adjusting for rurality of practice, patient characteristics, and 2019 ED visit rates. Results: Data were analyzed for a total of 13 820 family physicians (7114 males [51.5%]; mean [SD] age, 50 [13.1] years) with 12 951 063 patients (6 714 150 females [51.8%]; mean [SD] age, 42.6 [22.9] years) who were attached to these physicians. Most physicians provided between 40% and 80% of care virtually. A higher percentage of the physicians who provided more than 80% of care virtually were 65 years or older, female individuals, and practiced in big cities. Patient comorbidity and morbidity were similar across strata of virtual care use. The mean (SD) number of ED visits was highest among patients whose physicians provided only in-person care (470.3 [1918.8] per 1000 patients) and was lowest among patients of physicians who provided more than 80% to less than 100% of care virtually (242.0 [800.3] per 1000 patients). After adjustment for patient characteristics, patients of physicians with more than 20% of visits delivered virtually had lower rates of ED visits compared with patients of physicians who provided more than 0% to 20% of care virtually (eg, >80% to <100% vs >0%-20% virtual visits in big cities: relative rate, 0.77%; 95% CI, 0.74%-0.81%). This pattern was unchanged across all rurality of practice strata and after adjustment for 2019 ED visit rates. In urban areas, there was a gradient whereby patients of physicians providing the highest level of virtual care had the lowest ED visit rates. Conclusions and Relevance: Findings of this study show that patients of physicians who provided a higher percentage of virtual care did not have higher ED visit rates compared with patients of physicians who provided the lowest levels of virtual care. The findings refute the hypothesis that family physicians providing more care virtually during the pandemic resulted in higher ED use.

Predicting localised corrosion and mechanical performance of a PEO surface modified rare earth magnesium alloy for implant use through in-silico modelling.

In this study, the influence of a plasma electrolytic oxidation (PEO) surface treatment on a medical-grade WE43-based magnesium alloy is examined through an experimental and computational framework that considers the effects of localised corrosion features and mechanical properties throughout the corrosion process. First, a comprehensive in-vitro immersion study was performed on WE43-based tensile specimens with and without PEO surface modification, which included fully automated spatial reconstruction of the phenomenological features of corrosion through micro-CT scanning, followed by uniaxial tensile testing. Then the experimental data of both unmodified and PEO-modified groups were used to calibrate parameters of a finite element-based surface corrosion model. In-vitro, it was found that the WE43-PEO modified group had a significantly lower corrosion rate and maintained significantly higher mechanical properties than the unmodified. While corrosion rates were ∼50% lower in the WE43-PEO modified specimens, the local geometric features of corroding surfaces remained similar to the unmodified WE43 group, however evolving after almost the double amount of time. We were also able to quantitatively demonstrate that the PEO surface treatment on magnesium continued to protect samples from corrosion throughout the entire period tested, and not just in the early stages of corrosion. Using the results from the testing framework, the model parameters of the surface-based corrosion model were identified for both groups. This enabled, for the first time, in-silico prediction of the physical features of corrosion and the mechanical performance of both unmodified and PEO modified magnesium specimens. This simulation framework can enable future in-silico design and optimisation of bioabsorbable magnesium devices for load-bearing medical applications.

Bioabsorbable WE43 Mg alloy wires modified by continuous plasma electrolytic oxidation for implant applications. Part II: Degradation and biological performance.

The corrosion, mechanical degradation and biological performance of cold-drawn WE43 Mg wires were analyzed as a function of thermo-mechanical processing and the presence of a protective oxide layer created by continuous plasma electrolytic oxidation (PEO). It was found that the corrosion properties of the non-surface-treated wire could be optimized by means of thermal treatment within certain limits, but the corrosion rate remained very high. Hence, strength and ductility of these wires vanished after 24 h of immersion in simulated body fluid at 37 °C and, as a result of that rather quick degradation, direct tests did not show any MC3T3-E1 preosteoblast cell attachment on the surface of the Mg wires. In contrast, surface modification of the annealed WE43 Mg wires by a continuous PEO process led to the formation of a homogeneous oxide layer of ≈8 µm and significantly improved the corrosion resistance and hence the biocompatibility of the WE43 Mg wires. It was found that a dense layer of Ca/P was formed at the early stages of degradation on top of the Mg(OH)2 layer and hindered the diffusion of the Cl- ions which dissolve Mg(OH)2 and accelerate the corrosion of Mg alloys. As a result, pitting corrosion was suppressed and the strength of the Mg wires was above 100 MPa after 96 h of immersion in simulated body fluid at 37 °C. Moreover, many cells were able to attach on the surface of the PEO surface-modified wires during cell culture testing. These results demonstrate the potential of thin Mg wires surface-modified by continuous PEO in terms of mechanical, degradation and biological performance for bioabsorbable wire-based devices.

Bioabsorbable WE43 Mg alloy wires modified by continuous plasma-electrolytic oxidation for implant applications. Part I: Processing, microstructure and mechanical properties.

In our work, a novel processing strategy for the continuous fabrication and surface modification of wires from Magnesium alloy WE43 by means of plasma-electrolytic oxidation (PEO) is presented. In the first step, wires with a strong basal texture and small grain size (≈ 1 µm) were manufactured by combined cold drawing and in-line stress-relief heat treatment steps that optimized the mechanical properties (in terms of strength and ductility) by means of annealing. In a second step, and to the best of our knowledge for the first time ever, the wires were continuously surface-modified with a novel plasma electrolytic oxidation process, which was able to create a homogeneous porous oxide layer made of MgO and Mg3(PO4)2 on the wire surface. While the oxide layer slightly diminished the tensile properties, the strength of the surface-modified wires could be maintained close to 300 MPa with a strain-to-failure ≈ 8 %. Furthermore, the thickness of the oxide layer could be controlled by immersion time within the electrolytic bath and was adjusted to realize a thicknesses of ≈ 8 µm, which could be obtained in <20 s. Our experiments showed that the chemical composition, morphology and porosity of the oxide layer could be tailored by changing electrical parameters. The combined cold drawing and heat treatment process with additional continuous plasma electrolytic oxidation processing can be upscaled to produce a novel generation of bioabsorbable Mg wires with optimized mechanical, degradation and biological performance for use in biomedical applications.

An enhanced phenomenological model to predict surface-based localised corrosion of magnesium alloys for medical use.

This study developed an enhanced phenomenological model for the predictions of surface-based localised corrosion of magnesium alloys for use in medical applications. The modelling framework extended previous surface-based approaches by considering the role of ß-phase components throughout the material volume to better predict spatial and temporal aspects of surface-based corrosion in magnesium alloys. This enhanced surface-based corrosion model offers many advantages as it (i) captures multi-directional pitting, (ii) captures various pit morphologies, (iii) eliminates mesh sizing effects, (iv) reduces computational cost through custom time controls (v) offers control of pit sizing and (vi) produces corrosion rates that are independent of pitting parameter values. The model was fully implemented in three dimensions within the finite element framework and shows excellent potential to enable robust predictions of the long-term performance of magnesium-based implants undergoing corrosion.

Long-term in vivo observations show biocompatibility and performance of ZX00 magnesium screws surface-modified by plasma-electrolytic oxidation in Göttingen miniature pigs.

Bioabsorbable magnesium implants for orthopedic fixation of bone have recently become available for different fields of indication. While general questions of biocompatibility have been answered, tailoring suitable degradation kinetics for specific applications as well as long-term tissue integration remain the focus of current research. The aim of this study was the evaluation of the long-term degradation behavior and osseointegration of Mg-Ca-Zn (ZX00MEO) based magnesium implants with plasma-electrolytic oxidation (PEO) surface modification (ZX00MEO-PEO) in comparison to non-surface modified implants in vivo and in vitro. Besides a general evaluation of the biological performance of the alloy over a prolonged period, the main hypothesis was that PEO surface modification significantly reduces implant degradation rate and improves tissue interaction. In vitro, the microstructure and surface of the bioabsorbable screws were characterized by SEM/EDS, cytocompatibility and degradation testing facilitating hydrogen gas evolution, carried out following ISO 10993-5/-12 and ASTM F3268-18a/ASTM G1-03 (E1:2017). In vivo, screws were implanted in the frontal bone of Minipigs for 6, 12, and 18 months, following radiological and histomorphometric analysis. A slower and more uniform degradation and improved cytocompatibility could be shown for the ZX00MEO-PEO group in vitro. A significant reduction of degradation rate and enhanced bone formation around the ZX00MEO-PEO screws in vivo was confirmed. Proficient biocompatibility and tissue integration could generally be shown in vivo regardless of surface state. The tested magnesium alloy shows generally beneficial properties as an implant material, while PEO-surface modification further improves the bioabsorption behavior both in vitro and in vivo. STATEMENT OF SIGNIFICANCE: Devices from bioabsorbable Magnesium have recently been introduced to orthopedic applications. However, the vast degradation of Magnesium within the human body still gives limitations. While reliable in-vivo data on most promising surface treatments such as Plasma-electrolytic-Oxidation is generally scarce, long-time results in large animals are to this date completely missing. To overcome this lack of evidence, we studied a Magnesium-Calzium-Zinc-alloy with surface enhancement by PEO for the first time ever over a period of 18 months in a large animal model. In-vitro, surface-modified screws showed significantly improved cytocompatibility and reduction of degradation confirmed by hydrogen gas evolution testing, while in-vivo radiological and histological evaluation generally showed good biocompatibility and bioabsorption as well as significantly enhanced reduction of degradation and faster bone regeneration in the PEO-surface-modified group.

Impact of antegrade enema initiation on healthcare utilization in pediatric patients: A population-based cohort study.

BACKGROUND: When constipation is refractory to first-line interventions, antegrade enema use may be considered. We aimed to assess the impact of this intervention on healthcare utilization. METHODS: We conducted a population-based, quasi-experimental study with pre-post comparison of the intervention group and a non-equivalent control group using linked clinical and health administrative data from Ontario, Canada. Subjects included children (0-18 years) who underwent antegrade enema initiation from 2007 to 2020 and matched controls (4:1) from the general population. To assess the change in healthcare utilization following antegrade enema initiation, we used negative binomial generalized estimating equations with covariates selected a priori. KEY RESULTS: One hundred thirty-eight subjects met eligibility criteria (appendicostomy = 55 (39.9%); cecostomy tube = 83 (60.1%)) and were matched to 550 controls. There was no significant difference in the change in the rate of hospitalizations (rate ratio (RR) 1.05, 95% confidence interval (CI) 0.35-1.75), outpatient visits (RR 1.05, 95% CI 0.91-1.18), or same-day surgical procedures (RR 1.51, 95% CI 0.60-2.43) across cases in 2 years following antegrade enema initiation compared with controls. Cases had an increased rate of emergency department (ED) visits, which was not observed in controls (RR 1.52, 95% CI 1.11-1.79), driven in part by device-related complications. CONCLUSIONS AND INFERENCES: Understanding healthcare utilization patterns following antegrade enema initiation allows for effective health system planning and aids medical decision-making. The observed increase in ED visits for device-related complications speaks to the need to improve preventive management to help mitigate emergency care after initiation of antegrade enemas.

Linking the effect of localised pitting corrosion with mechanical integrity of a rare earth magnesium alloy for implant use.

This study presents a computational framework that investigates the effect of localised surface-based corrosion on the mechanical performance of a magnesium-based alloy. A finite element-based phenomenological corrosion model was used to generate a wide range of corrosion profiles, with subsequent uniaxial tensile test simulations to predict the mechanical response to failure. The python-based detection framework PitScan provides detailed quantification of the spatial phenomenological features of corrosion, including a full geometric tracking of corroding surface. Through this approach, this study is the first to quantitatively demonstrate that a surface-based non-uniform corrosion model can capture both the geometrical and mechanical features of a magnesium alloy undergoing corrosion by comparing to experimental data. Using this verified corrosion modelling approach, a wide range of corrosion scenarios was evaluated and enabled quantitative relationships to be established between the mechanical integrity and key phenomenological corrosion features. In particular, we demonstrated that the minimal cross-sectional area parameter was the strongest predictor of the remaining mechanical strength (R2 = 0.98), with this relationship being independent of the severity or spatial features of localised surface corrosion. Interestingly, our analysis demonstrated that parameters described in ASTM G46-94 showed weaker correlations to the mechanical integrity of corroding specimens, compared to parameters determined by Pitscan. This study establishes new mechanistic insight into the performance of the magnesium-based materials undergoing corrosion.

Changes in Service Delivery and Access to Rheumatologists Before and During the COVID-19 Pandemic in a Canadian Universal Healthcare Setting.

OBJECTIVE: To describe changes in service delivery and access to rheumatologists before and during the coronavirus disease 2019 (COVID-19) pandemic periods. METHODS: We conducted a population-based study in Ontario, Canada. Patient visits with rheumatologists were ascertained using billing claims data. Contact with rheumatologists was defined separately by the type of patient encounter (including office visits, telemedicine visits, and new patient consultations). Changes in the total weekly volume of encounters and monthly rates after COVID-19 public health measures were imposed were compared to expected baseline rates determined before pandemic onset (March 17, 2020). RESULTS: In the year prior to the pandemic, there were 289,202 patients (of which 96,955 were new consults) seen by 239 rheumatologists. In the 1 year following the pandemic onset, there were 276,686 patients (of which 86,553 were new consults) seen by 247 rheumatologists. In March 2020, there was an immediate 75.9% decrease in outpatient office visits and a rapid rise in telemedicine visits. By September 2021, 49.7% of patient encounters remained telemedicine visits. For new patient consultations, there was an immediate 50% decrease in visits at the pandemic onset, with 54.8% diverted to telemedicine visits in the first year of the pandemic versus 37.4% by September 2021. New rheumatology consultation rates continued decreasing over the study period. CONCLUSION: Rheumatology care delivery has shifted due to the pandemic, with telemedicine increasing sharply early in the pandemic and persisting over time. The pandemic also negatively affected access to rheumatologists, resulting in fewer new consultations and raising concerns for potential delays to diagnosis.

Family Physicians Stopping Practice During the COVID-19 Pandemic in Ontario, Canada.

We conducted 2 analyses using administrative data to understand whether more family physicians in Ontario, Canada stopped working during the COVID-19 pandemic compared with previous years. First, we found 3.1% of physicians working in 2019 (n = 385/12,247) reported no billings in the first 6 months of the pandemic; compared with other family physicians, a higher portion were aged 75 years or older (13.0% vs 3.4%, P <0.001), had fee-for-service reimbursement (37.7% vs 24.9%, P <0.001), and had a panel size under 500 patients (40.0% vs 25.8%, P <0.001). Second, a fitted regression line found the absolute increase in the percentage of family physicians stopping work was 0.03% per year from 2010 to 2019 (P = 0.042) but 1.2% between 2019 to 2020 (P <0.001). More research is needed to understand the impact of physicians stopping work on primary care attachment and access to care.

Biohybrid elastin-like venous valve with potential for in situ tissue engineering.

Chronic venous insufficiency (CVI) is a leading vascular disease whose clinical manifestations include varicose veins, edemas, venous ulcers, and venous hypertension, among others. Therapies targeting this medical issue are scarce, and so far, no single venous valve prosthesis is clinically available. Herein, we have designed a bi-leaflet transcatheter venous valve that consists of (i) elastin-like recombinamers, (ii) a textile mesh reinforcement, and (iii) a bioabsorbable magnesium stent structure. Mechanical characterization of the resulting biohybrid elastin-like venous valves (EVV) showed an anisotropic behavior equivalent to the native bovine saphenous vein valves and mechanical strength suitable for vascular implantation. The EVV also featured minimal hemolysis and platelet adhesion, besides actively supporting endothelialization in vitro, thus setting the basis for its application as an in situ tissue engineering implant. In addition, the hydrodynamic testing in a pulsatile bioreactor demonstrated excellent hemodynamic valve performance, with minimal regurgitation (<10%) and pressure drop (<5 mmHg). No stagnation points were detected and an in vitro simulated transcatheter delivery showed the ability of the venous valve to withstand the implantation procedure. These results present a promising concept of a biohybrid transcatheter venous valve as an off-the-shelf implant, with great potential to provide clinical solutions for CVI treatment.

Antibacterial properties of functionalized silk fibroin and sericin membranes for wound healing applications in oral and maxillofacial surgery.

Oral wounds are among the most troublesome injuries which easily affect the patients' quality of life. To date, the development of functional antibacterial dressings for oral wound healing remains a challenge. In this regard, we investigated antibacterial silk protein-based membranes for the application as wound dressings in oral and maxillofacial surgery. The present study includes five variants of casted membranes, i.e., i) membranes-silver nanoparticles (CM-Ag), ii) membranes-gentamicin (CM-G), iii) membranes-control (without functionalization) (CM-C), iv) membranes-silk sericin control (CM-SSC), and v) membranes-silk fibroin/silk sericin (CM-SF/SS), and three variants of nonwovens, i.e., i) silver nanoparticles (NW-Ag), ii) gentamicin (NW-G), iii) control (without functionalization) (NW-C). The surface structure of the samples was visualized with scanning electron microscopy. In addition, antibacterial testing was accomplished using agar diffusion assay, colony forming unit (CFU) analysis, and qrt-PCR. Following antibacterial assays, biocompatibility was evaluated by cell proliferation assay (XTT), cytotoxicity assay (LDH), and live-dead assay on L929 mouse fibroblasts. Findings indicated significantly lower bacterial colony growth and DNA counts for CM-Ag with a reduction of bacterial counts by 3log levels (99.9% reduction) in CFU and qrt-PCR assay compared to untreated control membranes (CM-C and CM-SSC) and membranes functionalized with gentamicin (CM-G and NW-G) (p < 0.001). Similarly, NW-G yielded significantly lower DNA and colony growth counts compared to NW-Ag and NW-C (p < 0.001). In conclusion, CM-Ag represented 1log level better antibacterial activity compared to NW-G, whereas NW-G showed better cytocompatibility for L929 cells. As data suggest, these two membranes have the potential of application in the field of bacteria-free oral wound healing. However, provided that loading strategy and cytocompatibility are adjusted according to the antibacterial agents' characteristic and fabrication technique of the membranes.

Silk Fibroin as Adjuvant in the Fabrication of Mechanically Stable Fibrin Biocomposites.

Fibrin is a very attractive material for the development of tissue-engineered scaffolds due to its exceptional bioactivity, versatility in the fabrication, affinity to cell mediators; and the possibility to isolate it from blood plasma, making it autologous. However, fibrin application is greatly limited due to its low mechanical properties, fast degradation, and strong contraction in the presence of cells. In this study, we present a new strategy to overcome these drawbacks by combining it with another natural polymer: silk fibroin. Specifically, we fabricated biocomposites of fibrin (5 mg/mL) and silk fibroin (0.1, 0.5 and 1% w/w) by using a dual injection system, followed by ethanol annealing. The shear elastic modulus increased from 23 ± 5 Pa from fibrin alone, to 67 ± 22 Pa for fibrin/silk fibroin 0.1%, 241 ± 67 Pa for fibrin/silk fibroin 0.5% and 456 ± 32 Pa for fibrin/silk fibroin 1%. After culturing for 27 days with strong contractile cells (primary human arterial smooth muscle cells), fibrin/silk fibroin 0.5% and fibrin/silk fibroin 1% featured minimal cell-mediated contraction (ca. 15 and 5% respectively) in contrast with the large surface loss of the pure fibrin scaffolds (ca. 95%). Additionally, the composites enabled the formation of a proper endothelial cell layer after culturing with human primary endothelial cells under standard culture conditions. Overall, the fibrin/silk fibroin composites, manufactured within this study by a simple and scalable biofabrication approach, offer a promising avenue to boost the applicability of fibrin in tissue engineering.