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.

Challenges and Pitfalls of Research Designs Involving Magnesium-Based Biomaterials: An Overview.

Magnesium-based biomaterials hold remarkable promise for various clinical applications, offering advantages such as reduced stress-shielding and enhanced bone strengthening and vascular remodeling compared to traditional materials. However, ensuring the quality of preclinical research is crucial for the development of these implants. To achieve implant success, an understanding of the cellular responses post-implantation, proper model selection, and good study design are crucial. There are several challenges to reaching a safe and effective translation of laboratory findings into clinical practice. The utilization of Mg-based biomedical devices eliminates the need for biomaterial removal surgery post-healing and mitigates adverse effects associated with permanent biomaterial implantation. However, the high corrosion rate of Mg-based implants poses challenges such as unexpected degradation, structural failure, hydrogen evolution, alkalization, and cytotoxicity. The biocompatibility and degradability of materials based on magnesium have been studied by many researchers in vitro; however, evaluations addressing the impact of the material in vivo still need to be improved. Several animal models, including rats, rabbits, dogs, and pigs, have been explored to assess the potential of magnesium-based materials. Moreover, strategies such as alloying and coating have been identified to enhance the degradation rate of magnesium-based materials in vivo to transform these challenges into opportunities. This review aims to explore the utilization of Mg implants across various biomedical applications within cellular (in vitro) and animal (in vivo) models.

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.

Impact of Team-Based Care on Emergency Department Use.

PURPOSE: We sought to assess the impact of team-based care on emergency department (ED) use in the context of physicians transitioning from fee-for-service payment to capitation payment in Ontario, Canada. METHODS: We conducted an interrupted time series analysis to assess annual ED visit rates before and after transition from an enhanced fee-for-service model to either a team capitation model or a nonteam capitation model. We included Ontario residents aged 19 years and older who had at least 3 years of outcome data both pretransition and post-transition (N = 2,524,124). We adjusted for age, sex, income quintile, immigration status, comorbidity, and morbidity, and we stratified by rurality. A sensitivity analysis compared outcomes for team vs nonteam patients matched on year of transition, age, sex, rurality, and health region. RESULTS: We compared 387,607 team and 1,399,103 nonteam patients in big cities, 213,394 team and 380,009 nonteam patients in small towns, and 65,289 team and 78,722 nonteam patients in rural areas. In big cities, after adjustment, the ED visit rate increased by 2.4% (95% CI, 2.2% to 2.6%) per year for team patients and 5.2% (95% CI, 5.1% to 5.3%) per year for nonteam patients in the years after transition (P <.001). Similarly, there was a slower increase in ED visits for team relative to nonteam patients in small towns (0.9% [95% CI, 0.7% to 1.1%] vs 2.9% [95% CI, 2.8% to 3.1%], P <.001) and rural areas (‒0.5% [95% CI, -0.8% to 0.2%] vs 1.3% [95% CI, 1.0% to 1.6%], P <.001). Results were much the same in the matched analysis. CONCLUSIONS: Adoption of team-based primary care may reduce ED use. Further research is needed to understand optimal team composition and roles.

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.

Air Pollution as a Risk Factor for Incident Chronic Obstructive Pulmonary Disease and Asthma. A 15-Year Population-based Cohort Study.

Rationale: Current evidence on the relationship between long-term exposure to air pollution and new onset of chronic lung disease is inconclusive.Objectives: To examine associations of incident chronic obstructive pulmonary disease (COPD) and adult-onset asthma with past exposure to fine particulate matter ≤ 2.5 µm in diameter (PM2.5), nitrogen dioxide (NO2), ozone (O3), and the redox-weighted average of NO2 and O3 (Ox) and characterize the concentration-response relationship.Methods: We conducted a population-based cohort study of all Ontarians, aged 35-85 years, from 2001 to 2015. A 3-year moving average of residential exposures to selected pollutants with a 1-year lag were estimated during follow-up. We used Cox proportional hazard models and Aalen additive-hazard models to quantify the pollution-disease associations and characterized the shape of these relationships using newly developed nonlinear risk models.Measurements and Main Results: Among 5.1 million adults, we identified 340,733 and 218,005 incident cases of COPD and asthma, respectively. We found positive associations of COPD with PM2.5 per interquartile-range (IQR) increase of 3.4 µg/m3 (hazard ratio, 1.07; 95% confidence interval, 1.06-1.08), NO2 per IQR increase of 13.9 ppb (1.04; 1.02-1.05), O3 per IQR increase of 6.3 ppb (1.04; 1.03-1.04), and Ox per IQR increase of 4.4 ppb (1.03; 1.03-1.03). By contrast, we did not find strong evidence linking these pollutants to adult-onset asthma. In addition, we quantified that each IQR increase in pollution exposure yielded 3.0 (2.4-3.6), 3.2 (2.0-4.3), 1.9 (1.3-2.5), and 2.3 (1.7-2.9) excess cases of COPD per 100,000 adults for PM2.5, NO2, O3, and Ox, respectively. Furthermore, most pollutant-COPD relationships exhibited supralinear shapes.Conclusions: Air pollution was associated with a higher incidence of COPD but was not associated with a higher incidence of adult-onset asthma.

Correlates of non-adherence to breast, cervical, and colorectal cancer screening among screen-eligible women: a population-based cohort study in Ontario, Canada.

PURPOSE: Breast, cervical, and colorectal cancers are cancers that can be detected early through screening. Despite organized cancer screening programs in Ontario, Canada participation remains low among marginalized populations. Although extensive research has been done about factors contributing to under-screening by cancer site, the predictors of under/never screened conjointly for all three types of cancer remain unknown. METHODS: Using provincial-level linked administrative data sets, we examined Ontario women who were screen-eligible for all three types of cancer over a 36-month period (i.e., April 2014-March 2017) and determined how many were up to date on 0, 1, 2, and all three types of screenings. Multivariate logistic regression was utilized to examine individual and structural predictors of screening with the group overdue for all screening being the reference group. RESULTS: Of the 1,204,551 screen-eligible women, 15% were overdue for all. Living in the lowest income neighborhoods (AOR 0.46 [95% CI 0.45-0.47]), being recent immigrants (AOR 0.54 [95% CI 0.53-0.55]), having no primary care provider (AOR 0.17 [95% CI 0.16-0.17]), and having no contact with health care services (AOR 0.09 [95% CI 0.09-0.09]) significantly increased the likelihood of being overdue for all versus no screening type. CONCLUSIONS: Considering that more than 15% of screen-eligible women in Ontario were overdue for all types of cancer screening, it is imperative to address structural barriers such as lack of a primary care provider. Innovative interventions like "one-stop shopping" where screening for different cancers can be offered at the same time could promote screening uptake.

High prevalence of comorbidities at diagnosis in immigrants with multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) has been associated with certain comorbidities in general population studies, but it is unknown how comorbidity may affect immigrants with MS. OBJECTIVE: To compare prevalence of comorbidities in immigrants and long-term residents at MS diagnosis, and in matched control populations without MS. METHODS: We identified incident MS cases using a validated definition applied to health administrative data in Ontario, Canada, from 1994 to 2017, and categorized them as immigrants or long-term residents. Immigrants and long-term residents without MS (controls) were matched to MS cases 3:1 on sex, age, and geography. RESULTS: There were 1534 immigrants and 23,731 long-term residents with MS matched with 4585 and 71,193 controls, respectively. Chronic obstructive pulmonary disease (COPD), diabetes, hypertension, ischemic heart disease, migraine, epilepsy, mood/anxiety disorders, schizophrenia, inflammatory bowel disease (IBD), and rheumatoid arthritis were significantly more prevalent among immigrants with MS compared to their controls. Prevalence of these conditions was generally similar comparing immigrants to long-term residents with MS, although COPD, epilepsy, IBD, and mood/anxiety disorders were less prevalent in immigrants. CONCLUSION: Immigrants have a high prevalence of multiple comorbidities at MS diagnosis despite the "healthy immigrant effect." Clinicians should pay close attention to identification and management of comorbidity in immigrants with MS.

Shifts in office and virtual primary care during the early COVID-19 pandemic in Ontario, Canada.

BACKGROUND: Globally, primary care changed dramatically as a result of the coronavirus disease 2019 (COVID-19) pandemic. We aimed to understand the degree to which office and virtual primary care changed, and for which patients and physicians, during the initial months of the pandemic in Ontario, Canada. METHODS: This population-based study compared comprehensive, linked primary care physician billing data from Jan. 1 to July 28, 2020, with the same period in 2019. We identified Ontario residents with at least 1 office or virtual (telephone or video) visit during the study period. We compared trends in total physician visits, office visits and virtual visits before COVID-19 with trends after pandemic-related public health measures changed the delivery of care, according to various patient and physician characteristics. We used interrupted time series analysis to compare trends in the early and later halves of the COVID-19 period. RESULTS: Compared with 2019, total primary care visits between March and July 2020 decreased by 28.0%, from 7.66 to 5.51 per 1000 people/day. The smallest declines were among patients with the highest expected health care use (8.3%), those who could not be attributed to a primary care physician (10.2%), and older adults (19.1%). In contrast, total visits in rural areas increased by 6.4%. Office visits declined by 79.1% and virtual care increased 56-fold, comprising 71.1% of primary care physician visits. The lowest uptake of virtual care was among children (57.6%), rural residents (60.6%) and physicians with panels of ≥ 2500 patients (66.0%). INTERPRETATION: Primary care in Ontario saw large shifts from office to virtual care over the first 4 months of the COVID-19 pandemic. Total visits declined least among those with higher health care needs. The determinants and consequences of these major shifts in care require further study.

Ethnic and Immigrant Variations in the Time Trends of Dementia and Parkinsonism.

OBJECTIVE: We assessed long-term incidence and prevalence trends of dementia and parkinsonism across major ethnic and immigrant groups in Ontario. METHODS: Linking administrative databases, we established two cohorts (dementia 2001-2014 and parkinsonism 2001-2015) of all residents aged 20 to 100 years with incident diagnosis of dementia (N = 387,937) or parkinsonism (N = 59,617). We calculated age- and sex-standardized incidence and prevalence of dementia and parkinsonism by immigrant status and ethnic groups (Chinese, South Asian, and the General Population). We assessed incidence and prevalence trends using Poisson regression and Cochran-Armitage trend tests. RESULTS: Across selected ethnic groups, dementia incidence and prevalence were higher in long-term residents than recent or longer-term immigrants from 2001 to 2014. During this period, age- and sex-standardized incidence of dementia in Chinese, South Asian, and the General Population increased, respectively, among longer-term immigrants (by 41%, 58%, and 42%) and long-term residents (28%, 7%, and 4%), and to a lesser degree among recent immigrants. The small number of cases precluded us from assessing parkinsonism incidence trends. For Chinese, South Asian, and the General Population, respectively, prevalence of dementia and parkinsonism modestly increased over time among recent immigrants but significantly increased among longer-term immigrants (dementia: 134%, 217%, and 117%; parkinsonism: 55%, 54%, and 43%) and long-term residents (dementia: 97%, 132%, and 71%; parkinsonism: 18%, 30%, and 29%). Adjustment for pre-existing conditions did not appear to explain incidence trends, except for stroke and coronary artery disease as potential drivers of dementia incidence. CONCLUSION: Recent immigrants across major ethnic groups in Ontario had considerably lower rates of dementia and parkinsonism than long-term residents, but this difference diminished with longer-term immigrants.

Exposure to ambient air pollution and the incidence of lung cancer and breast cancer in the Ontario Population Health and Environment Cohort.

Lung and female breast cancers are highly prevalent worldwide. Although the association between exposure to ambient fine particulate matter (PM2.5 ) and lung cancer has been recognized, there is less evidence for associations with other common air pollutants such as nitrogen dioxide (NO2 ) and ozone (O3 ). Even less is known about potential associations between these pollutants and breast cancer. We conducted a population-based cohort study to investigate the associations of chronic exposure to PM2.5 , NO2 , O3 and redox-weighted average of NO2 and O3 (Ox ) with incident lung and breast cancer, using the Ontario Population Health and Environment Cohort (ONPHEC), which includes all long-term residents aged 35-85 years who lived in Ontario, Canada, 2001-2015. Incident lung and breast cancers were ascertained using the Ontario Cancer Registry. Annual estimates of exposures were assigned to the residential postal codes of subjects for each year during follow-up. We used Cox proportional-hazards models adjusting for personal- and neighborhood-level covariates. Our cohorts for lung and breast cancer analyses included ~4.9 million individuals and ~2.5 million women, respectively. During follow-up, 100,146 incident cases of lung cancer and 91,146 incident cases of breast cancer were diagnosed. The fully adjusted analyses showed positive associations of lung cancer incidence with PM2.5 (hazard ratio [HR] = 1.02 [95% CI: 1.01-1.05] per 5.3 µg/m3 ) and NO2 (HR = 1.05 [95% CI: 1.03-1.07] per 14 ppb). No associations with lung cancer were observed for O3 or Ox . Relationships between PM2.5 and NO2 with lung cancer exhibited a sublinear shape. We did not find compelling evidence linking air pollution to breast cancer.

In vitro study on the hemocompatibility of plasma electrolytic oxidation coatings on titanium substrates.

Passively levitated ventricular assist devices (VADs) are vulnerable to impeller-housing contact and could benefit from surface coatings that improve wear resistance. Such coatings can be manufactured by plasma electrolytic oxidation (PEO), but their suitability for blood-contact applications needs further investigation. We therefore compared blood-surface interactions of polished titanium grade 5 (Ti Gr 5), as a general VAD reference material, uncoated ground titanium grade 4 (Ti Gr 4) and two commercially available PEO coatings on Ti Gr 4. In n = 4 static platelet adhesion tests, material samples were incubated with platelet-rich plasma (PRP) and consecutively analyzed for adhesive platelets by immunofluorescence microscopy. Additionally, PRP supernatant of incubated material samples was analyzed for changes in antithrombin III and fibrinogen concentrations by turbodimetry and enzyme-linked immunosorbent assay, respectively. We could not find any significant differences between the materials in the analyzed hemocompatibility markers (P > .05). Thus, we conclude that PEO coatings might offer a similar hemocompatibility to that of polished Ti Gr 5 and uncoated Ti Gr 4. Nevertheless, future studies should investigate blood-surface interactions of PEO coatings under realistic VAD-related flow conditions to better evaluate their potential for VAD applications.

Acute and outpatient service utilisation prior to, during, and following enrolment in community-based mental health treatment among children and youth in Central Ontario: A proof of concept for cross-sectoral data linkage.

AIM: Given the fragmentation of mental health and addictions (MHA) services for children and youth, comprehensive data on utilisation patterns are lacking. We sought to describe MHA-related service use across the community, acute and outpatient sectors. METHODS: We used linked health-administrative data sets to identify a cohort of individuals aged <18 who received MHA treatment in a large community organisation in Ontario, Canada between 1 April 2007 and 31 March 2012. We described their socio-demographic characteristics, examined their MHA-related concurrent service use in acute care and outpatient physician settings (primary care providers, paediatricians and psychiatrists), and compared service utilisation prior to, during and following enrolment using Poisson regressions. RESULTS: Among 7285 children and youth receiving community MHA treatment, there were 481 concurrent MHA-related emergency department visits, 173 hospitalisations and 12140 outpatient physician visits. The average age at enrolment was 10.5 years, and 64% of clients were enrolled for ≥3 months. MHA-related emergency department use significantly declined from 1 year prior, compared to 1 year following receipt of community MHA treatment (112 vs. 82 visits per 1000 person-years, P < 0.001), particularly in females, ages 10-14, those living in higher-income neighbourhoods and urban areas, and those with anxiety disorders. MHA hospitalisations also declined (45 vs. 32, P < 0.001), while outpatient physician visits increased (1750 vs. 1874, P < 0.001). CONCLUSIONS: Our study suggests that community-based MHA treatment may be effective in diverting children and youth away from acute care and highlights the importance of data linkage as a means to better understand the complexity of cross-sectoral MHA service use.

Influence of the Casting Concentration on the Mechanical and Optical Properties of FA/CaCl2-Derived Silk Fibroin Membranes.

In this study, we describe the manufacturing and characterization of silk fibroin membranes derived from the silkworm Bombyx mori. To date, the dissolution process used in this study has only been researched to a limited extent, although it entails various potential advantages, such as reduced expenses and the absence of toxic chemicals in comparison to other conventional techniques. Therefore, the aim of this study was to determine the influence of different fibroin concentrations on the process output and resulting membrane properties. Casted membranes were thus characterized with regard to their mechanical, structural and optical assets via tensile testing, SEM, light microscopy and spectrophotometry. Cytotoxicity was evaluated using BrdU, XTT, and LDH assays, followed by live-dead staining. The formic acid (FA) dissolution method was proven to be suitable for the manufacturing of transparent and mechanically stable membranes. The fibroin concentration affects both thickness and transparency of the membranes. The membranes did not exhibit any signs of cytotoxicity. When compared to other current scientific and technical benchmarks, the manufactured membranes displayed promising potential for various biomedical applications. Further research is nevertheless necessary to improve reproducible manufacturing, including a more uniform thickness, less impurity and physiological pH within the membranes.

Associations of Long-Term Exposure to Ultrafine Particles and Nitrogen Dioxide With Increased Incidence of Congestive Heart Failure and Acute Myocardial Infarction.

Although long-term exposure to traffic-related air pollutants such as nitrogen dioxide has been linked to cardiovascular disease (CVD) mortality, little is known about the association between ultrafine particles (UFPs), defined as particles less than or equal to 0.1 µm in diameter, and incidence of major CVD events. We conducted a population-based cohort study to assess the associations of chronic exposure to UFPs and nitrogen dioxide with incident congestive heart failure (CHF) and acute myocardial infarction. Our study population comprised all long-term Canadian residents aged 30-100 years who lived in Toronto, Ontario, Canada, during the years 1996-2012. We estimated annual concentrations of UFPs and nitrogen dioxide by means of land-use regression models and assigned these estimates to participants' postal-code addresses in each year during the follow-up period. We estimated hazard ratios for the associations of UFPs and nitrogen dioxide with incident CVD using random-effects Cox proportional hazards models. We controlled for smoking and obesity using an indirect adjustment method. Our cohorts comprised approximately 1.1 million individuals at baseline. In single-pollutant models, each interquartile-range increase in UFP exposure was associated with increased incidence of CHF (hazard ratio for an interquartile-range increase (HRIQR) = 1.03, 95% confidence interval (CI): 1.02, 1.05) and acute myocardial infarction (HRIQR = 1.05, 95% CI: 1.02, 1.07). Adjustment for fine particles and nitrogen dioxide did not materially change these estimated associations. Exposure to nitrogen dioxide was also independently associated with higher CHF incidence (HRIQR = 1.04, 95% CI: 1.03, 1.06).

Understanding those overdue for cancer screening by five years or more: A retrospective cohort study in Ontario, Canada.

Populations that are more than just slightly overdue for breast, cervical and colorectal screening should likely be targeted for policy and practice interventions. We used provincial-level administrative data to describe the Ontario population who are screen-eligible for breast, cervical and colorectal cancers but overdue by at least five years. For each cancer screening type, we created three cohorts and a binary outcome: screened at least once in the previous five years or not, using March 31, 2017 as our index date. We conducted simple descriptive analyses as well as multivariable logistic regression, where age category, immigrant status, neighbourhood income quintile, region, urban/suburban/rural status, primary care model type, and healthcare utilization were included in the models. More than 20% of Ontarians eligible for each of breast, cervical and colorectal cancer screening respectively had no history of screening in the previous five years. In multivariable analyses, people were significantly more likely to have no recent screening history if they lived in lower-income neighbourhoods (e.g. adjusted odds ratio [95% confidence interval]: 0.59 [0.58-0.59] for cervical screening), were recent immigrants, did not have a primary care provider, had a provider who practiced in a traditional fee-for-service model. Despite the presence of three provincial organized screening programs, we have found that more than one-fifth of Ontarians who are eligible for each of breast, cervical and colorectal screening respectively have not been screened for five years or more. Ensuring that all Ontarians have access to high-quality primary care, may be crucial to increasing screening uptake.

Time Trends of the Incidence, Prevalence, and Mortality of Parkinsonism.

OBJECTIVES: We assessed trends in the incidence, prevalence, and post-diagnosis mortality of parkinsonism in Ontario, Canada over 18 years. We also explored the influence of a range of risk factors for brain health on the trend of incident parkinsonism. METHODS: We established an open cohort by linking population-based health administrative databases from 1996 to 2014 in Ontario. The study population comprised residents aged 20-100 years with an incident diagnosis of parkinsonism ascertained using a validated algorithm. We calculated age- and sex-standardized incidence, prevalence, and mortality of parkinsonism, stratified by young onset (20-39 years) and mid/late onset (≥40 years). We assessed trends in incidence using Poisson regression, mortality using negative binomial regression, and prevalence of parkinsonism and pre-existing conditions (e.g., head injury) using the Cochran-Armitage trend test. To better understand trends in the incidence of mid/late-onset parkinsonism, we adjusted for various pre-existing conditions in the Poisson regression model. RESULTS: From 1996 to 2014, we identified 73,129 incident cases of parkinsonism (source population of ∼10.5 million), of whom 56% were male, mean age at diagnosis was 72.6 years, and 99% had mid/late-onset parkinsonism. Over 18 years, the age- and sex-standardized incidence decreased by 13.0% for mid/late-onset parkinsonism but remained unchanged for young-onset parkinsonism. The age- and sex-standardized prevalence increased by 22.8%, while post-diagnosis mortality decreased by 5.5%. Adjustment for pre-existing conditions did not appreciably explain the declining incidence of mid/late-onset parkinsonism. CONCLUSION: Young-onset and mid/late-onset parkinsonism exhibited differing trends in incidence over 18 years in Ontario. Further research to identify other factors that may appreciably explain trends in incident parkinsonism is warranted.

In Vivo Simulation of Magnesium Degradability Using a New Fluid Dynamic Bench Testing Approach.

The degradation rate of magnesium (Mg) alloys is a key parameter to develop Mg-based biomaterials and ensure in vivo-mechanical stability as well as to minimize hydrogen gas production, which otherwise can lead to adverse effects in clinical applications. However, in vitro and in vivo results of the same material often differ largely. In the present study, a dynamic test bench with several single bioreactor cells was constructed to measure the volume of hydrogen gas which evolves during magnesium degradation to indicate the degradation rate in vivo. Degradation medium comparable with human blood plasma was used to simulate body fluids. The media was pumped through the different bioreactor cells under a constant flow rate and 37 °C to simulate physiological conditions. A total of three different Mg groups were successively tested: Mg WE43, and two different WE43 plasma electrolytically oxidized (PEO) variants. The results were compared with other methods to detect magnesium degradation (pH, potentiodynamic polarization (PDP), cytocompatibility, SEM (scanning electron microscopy)). The non-ceramized specimens showed the highest degradation rates and vast standard deviations. In contrast, the two PEO samples demonstrated reduced degradation rates with diminished standard deviation. The pH values showed above-average constant levels between 7.4-7.7, likely due to the constant exchange of the fluids. SEM revealed severe cracks on the surface of WE43 after degradation, whereas the ceramized surfaces showed significantly decreased signs of corrosion. PDP results confirmed the improved corrosion resistance of both PEO samples. While WE43 showed slight toxicity in vitro, satisfactory cytocompatibility was achieved for the PEO test samples. In summary, the dynamic test bench constructed in this study enables reliable and simple measurement of Mg degradation to simulate the in vivo environment. Furthermore, PEO treatment of magnesium is a promising method to adjust magnesium degradation.

Improved In Vitro Test Procedure for Full Assessment of the Cytocompatibility of Degradable Magnesium Based on ISO 10993-5/-12.

Magnesium (Mg)-based biomaterials are promising candidates for bone and tissue regeneration. Alloying and surface modifications provide effective strategies for optimizing and tailoring their degradation kinetics. Nevertheless, biocompatibility analyses of Mg-based materials are challenging due to its special degradation mechanism with continuous hydrogen release. In this context, the hydrogen release and the related (micro-) milieu conditions pretend to strictly follow in vitro standards based on ISO 10993-5/-12. Thus, special adaptions for the testing of Mg materials are necessary, which have been described in a previous study from our group. Based on these adaptions, further developments of a test procedure allowing rapid and effective in vitro cytocompatibility analyses of Mg-based materials based on ISO 10993-5/-12 are necessary. The following study introduces a new two-step test scheme for rapid and effective testing of Mg. Specimens with different surface characteristics were produced by means of plasma electrolytic oxidation (PEO) using silicate-based and phosphate-based electrolytes. The test samples were evaluated for corrosion behavior, cytocompatibility and their mechanical and osteogenic properties. Thereby, two PEO ceramics could be identified for further in vivo evaluations.

Living near major roads and the incidence of dementia, Parkinson's disease, and multiple sclerosis: a population-based cohort study.

BACKGROUND: Emerging evidence suggests that living near major roads might adversely affect cognition. However, little is known about its relationship with the incidence of dementia, Parkinson's disease, and multiple sclerosis. We aimed to investigate the association between residential proximity to major roadways and the incidence of these three neurological diseases in Ontario, Canada. METHODS: In this population-based cohort study, we assembled two population-based cohorts including all adults aged 20-50 years (about 4·4 million; multiple sclerosis cohort) and all adults aged 55-85 years (about 2·2 million; dementia or Parkinson's disease cohort) who resided in Ontario, Canada on April 1, 2001. Eligible patients were free of these neurological diseases, Ontario residents for 5 years or longer, and Canadian-born. We ascertained the individual's proximity to major roadways based on their residential postal-code address in 1996, 5 years before cohort inception. Incident diagnoses of dementia, Parkinson's disease, and multiple sclerosis were ascertained from provincial health administrative databases with validated algorithms. We assessed the associations between traffic proximity and incident dementia, Parkinson's disease, and multiple sclerosis using Cox proportional hazards models, adjusting for individual and contextual factors such as diabetes, brain injury, and neighbourhood income. We did various sensitivity analyses, such as adjusting for access to neurologists and exposure to selected air pollutants, and restricting to never movers and urban dwellers. FINDINGS: Between 2001, and 2012, we identified 243 611 incident cases of dementia, 31 577 cases of Parkinson's disease, and 9247 cases of multiple sclerosis. The adjusted hazard ratio (HR) of incident dementia was 1·07 for people living less than 50 m from a major traffic road (95% CI 1·06-1·08), 1·04 (1·02-1·05) for 50-100 m, 1·02 (1·01-1·03) for 101-200 m, and 1·00 (0·99-1·01) for 201-300 m versus further than 300 m (p for trend=0·0349). The associations were robust to sensitivity analyses and seemed stronger among urban residents, especially those who lived in major cities (HR 1·12, 95% CI 1·10-1·14 for people living <50 m from a major traffic road), and who never moved (1·12, 1·10-1·14 for people living <50 m from a major traffic road). No association was found with Parkinson's disease or multiple sclerosis. INTERPRETATION: In this large population-based cohort, living close to heavy traffic was associated with a higher incidence of dementia, but not with Parkinson's disease or multiple sclerosis. FUNDING: Health Canada (MOA-4500314182).