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.

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.

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.

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.

Improved in vivo osseointegration and degradation behavior of PEO surface-modified WE43 magnesium plates and screws after 6 and 12 months.

Magnesium is a highly promising candidate with respect to its future use as a material for resorbable implants. When magnesium degrades, hydrogen gas is released. High doses of gas emergence are reported to impair osseointegration and may therefore lead to fixation failure. The successful delay and reduction of the degradation rate by applying plasma electrolytic oxidation (PEO) as a post processing surface modification method for magnesium alloy has recently been demonstrated. The aim of this study was thus to compare the degradation behavior of a WE43-based plate system with and without respective PEO surface modification and to further investigate osseointegration, as well as the resulting effects on the surrounding bony tissue of both variants in a miniature pig model. WE43 magnesium screws and plates without (WE43) and with PEO surface modification (WE43-PEO) were implanted in long bones of Göttingen Miniature Pigs. At six and twelve months after surgery, micro-CT and histomorphometric analysis was performed. Residual screw volume (SV/TV; WE43: 28.8 ± 21.1%; WE43-PEO: 62.9 ± 31.0%; p = 0.027) and bone implant contact area (BIC; WE43: 18.1 ± 21.7%; WE43-PEO: 51.6 ± 27.7%; p = 0.015) were increased after six months among the PEO-modified implants. Also, surrounding bone density within the cortical bone was not affected by surface modification (BVTV; WE43: 76.7 ± 13.1%; WE43-PEO: 73.1 ± 16.2%; p = 0.732). Intramedullar (BV/TV; WE43: 33.2 ± 16.7%; WE43-PEO 18.4 ± 9.0%; p = 0.047) and subperiosteal (bone area; WE43: 2.6 ± 3.4 mm2; WE43-PEO: 6,9 ± 5.2 mm2; p = 0.049) new bone formation was found for both, surface-modified and non-surface-modified groups. After twelve months, no significant differences of SV/TV and BV/TV were found between the two groups. PEO surface modification of WE43 plate systems improved osseointegration and significantly reduced the degradation rate within the first six months in vivo. Osteoconductive and osteogenic stimulation by WE43 magnesium implants led to overall increased bone growth, when prior PEO surface modification was conducted.

Lung Cancer Inequalities in Stage of Diagnosis in Ontario, Canada.

Lung cancer is the most common cancer and cause of cancer death in Canada, with approximately 50% of cases diagnosed at stage IV. Sociodemographic inequalities in lung cancer diagnosis have been documented, but it is not known if inequalities exist with respect to immigration status. We used multiple linked health-administrative databases to create a cohort of Ontarians 40-105 years of age who were diagnosed with an incident lung cancer between 1 April 2012 and 31 March 2017. We used modified Poisson regression with robust standard errors to examine the risk of diagnosis at late vs. early stage among immigrants compared to long-term residents. The fully adjusted model included age, sex, neighborhood-area income quintile, number of Aggregated Diagnosis Group (ADG) comorbidities, cancer type, number of prior primary care visits, and continuity of care. Approximately 62% of 38,788 people with an incident lung cancer from 2012 to 2017 were diagnosed at a late stage. Immigrants to the province were no more likely to have a late-stage diagnosis than long-term residents (63.5% vs. 62.0%, relative risk (RR): 1.01 (95% confidence interval (CI): 0.99-1.04), adjusted relative risk (ARR): 1.02 (95% CI: 0.99-1.05)). However, in fully adjusted models, people with more comorbidities were less likely to have a late-stage diagnosis (adjusted relative risk (ARR): 0.82 (95% CI: 0.80-0.84) for those with 10+ vs. 0-5 ADGs). Compared to adenocarcinoma, small cell carcinoma was more likely to be diagnosed at a late stage (ARR: 1.29; 95% CI: 1.27-1.31), and squamous cell (ARR: 0.89; 95% CI: 0.87-0.91) and other lung cancers (ARR: 0.93; 95% CI: 0.91-0.94) were more likely to be diagnosed at an early stage. Men were also slightly more likely to have late-stage diagnosis in the fully adjusted model (ARR: 1.08; 95% CI: 1.05-1.08). Lung cancer in Ontario is a high-fatality cancer that is frequently diagnosed at a late stage. Having fewer comorbidities and being diagnosed with small cell carcinoma was associated with a late-stage diagnosis. The former group may have less health system contact, and the latter group has the lung cancer type most closely associated with smoking. As lung cancer screening programs start to be implemented across Canada, targeted outreach to men and to smokers, increasing awareness about screening, and connecting every Canadian with primary care should be system priorities.

A novel titanium implant surface modification by plasma electrolytic oxidation (PEO) preventing tendon adhesion.

Titanium is one of the most commonly used materials for implants in trauma applications due to its low density, high corrosion resistance and biocompatibility. Nevertheless, there is still a need for improved surface modifications of Titanium, in order to change surface properties such as wettability, antibacterial properties or tissue attachment. In this study, different novel plasma electrolytic oxidation (PEO) modifications have been investigated for tendon adhesion to implants commonly used in hand surgery. Titanium samples with four different PEO modifications were prepared by varying the electrolyte composition and analyzed with regards to their surface properties. Unmodified titanium blanks and Dotize® coating served as controls. Samples were examined using scanning electron microscopy (SEM), energy dispersive spectrometer (EDS), contact angle measuring system and analyzed for their biocompatibility and hemocompatibility (according to DIN ISO 10993-5 and 10,993-4). Finally, tendon adhesion of these specific surfaces were investigated by pull-off tests. Our findings show that surface thickness of PEO modifications was about 12-20 µm and had porous morphology. One modification demonstrated hydrophilic behavior accompanied by good biocompatibility without showing cytotoxic properties. Furthermore, no hemolytic effect and no significant influence on hemocompatibility were observed. Pull-off tests revealed a significant reduction of tendon adhesion by 64.3% (35.7% residual adhesion), compared to unmodified titanium (100%). In summary, the novel PEO-based ceramic-like porous modification for titanium surfaces might be considered a good candidate for orthopedic applications supporting a more efficient recovery.

Fracture Risk in Patients with Myasthenia Gravis: A Population-Based Cohort Study.

BACKGROUND: Prednisone is a common treatment for myasthenia gravis (MG), and osteoporosis is a known potential risk of chronic prednisone therapy. OBJECTIVE: Our aim was to evaluate the risk of serious fractures in a population-based cohort of MG patients. METHODS: An inception cohort of patients with MG was identified from administrative health data in Ontario, Canada between April 1, 2002 and December 31, 2015. For each MG patient, we matched 4 general population comparators based on age, sex, and region of residence. Fractures were identified through emergency department and hospitalization data. Crude overall rates and sex-specific rates of fractures were calculated for the MG and comparator groups, as well as rates of specific fractures. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression. RESULTS: Among 3,823 incident MG patients (followed for a mean of 5 years), 188 (4.9%) experienced a fracture compared with 741 (4.8%) fractures amongst 15,292 matched comparators. Crude fracture rates were not different between the MG cohort and matched comparators (8.71 vs. 7.98 per 1000 patient years), overall and in men and women separately. After controlling for multiple covariates, MG patients had a significantly lower risk of fracture than comparators (HR 0.74, 95% CI 0.63-0.88). CONCLUSIONS: In this large, population-based cohort of incident MG patients, MG patients were at lower risk of a major fracture than comparators. The reasons for this finding are unclear but may highlight the importance osteoporosis prevention.

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.

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.

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.

Influence of design and postprocessing parameters on the degradation behavior and mechanical properties of additively manufactured magnesium scaffolds.

Magnesium shows promising properties concerning its use in absorbable implant applications such as biodegradability, improved mechanical strength and plastic deformability. Following extensive research, the first fixation and compression screws composed of magnesium rare earth alloys were commercialised, notably in the field of orthopaedic surgery. Preclinical and clinical follow-up studies showed that the rapid degradation of unprotected metallic Magnesium surfaces and concomitant hydrogen gas bursts still raise concern regarding certain surgical indications and need to be further improved. In order to enlarge the scope of further applications, the development of future magnesium implants must aim at freedom of design and reduction of volume, hereby enabling higher functionalised implants, as e.g. plate systems or scaffold grafts for bone replacement therapy. In order to overcome the boundaries of conventional manufacturing methods such as turning or milling, the process of Laser Powder Bed Fusion (LPBF) for magnesium alloys was recently introduced. It enables the production of lattice structures, therefore allowing for reduction of implant material volume. Nevertheless, the concomitant increase of free surface of such magnesium scaffolds further stresses the aforementioned disadvantages of vast degradation and early loss of mechanical stability if not prevented by suitable postprocessing methods. Magnesium scaffold structures with different pore sizes were therefore manufactured by LPBF and consequently further modified either by thermal heat treatment or Plasma Electrolytic Oxidation (PEO). Implant performance was assessed by conducting degradation studies and mechanical testing. PEO modified scaffolds with small pore sizes exhibited improved long-term stability, while heat treated specimens showed impaired performance regarding degradation and mechanical stability. STATEMENT OF SIGNIFICANCE: Magnesium based scaffold structures offer wide possibilities for advanced functionalized bioabsorbable implants. By implementing lattice structures, big implant sizes and mechanically optimized implant geometries can be achieved enabling full bone replacement or large-scale plate systems, e.g. for orthopedic applications. As shape optimization and lattice structuring of such scaffolds consequently lead to enlarged surface, suitable design and postprocessing routines come into focus. The presented study addresses these new and relevant topics for the first time by evaluating geometry as well as heat and surface treatment options as input parameters for improved chemical and mechanical stability. The outcome of these variations is measured by degradation tests and mechanical analysis. Evaluating these methods, a significant contribution to the development of absorbable magnesium scaffolds is made. The findings can help to better understand the interdependence of high surface to volume ratio Magnesium implants and to deliver methods to incorporate such lattice structures into future large-scale implant applications manufactured from bioabsorbable Magnesium alloys.

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).

Impact of a provincial quality-improvement program on primary health care in Ontario: a population-based controlled before-and-after study.

BACKGROUND: In Ontario, a province-wide quality-improvement program (Quality Improvement and Innovation Partnership [QIIP]) was implemented between 2008 and 2010 to support improved outcomes in Family Health Teams, a care model that includes many features of the patient-centred medical home. We assessed the impact of this program on diabetes management, colorectal and cervical cancer screening and access to health care. METHODS: We used comprehensive linked administrative data sets to conduct a population-based controlled before-and-after study. Outcome measures included diabetes process-of-care measures (test ordering, retinal examination, medication prescribing and completion of billing items specific to diabetes management), colorectal and cervical cancer screening measures and use of health care services (emergency department visits, hospital admission for ambulatory-care-sensitive conditions and rates of readmission to hospital). The control group consisted of Family Health Team physicians with at least 100 assigned patients during the study follow-up period (November 2009-February 2013). RESULTS: There were 53 physicians in the intervention group and 1178 physicians in the control group. Diabetes process-of-care measures improved more in the intervention group than in the control group: hemoglobin A1c testing 4.3% (95% confidence interval [CI] 1.2-7.5) more, retinal examination 2.5% (95% CI 0.8-4.4) more and preventive care visits 8.9% (95% CI 2.9-14.9) more. Medication prescribing also improved for use of statins (3.4% [95% CI 0.8-6.0] more) and angiotensin-converting-enzyme inhibitors or angiotensin receptor blockers (4.1% [95% CI 1.8-6.4] more). Colorectal cancer screening improved 5.4% (95% CI 3.1-7.8) more in the intervention group than in the control group, and cervical cancer screening improved 2.7% (95% CI 0.9-4.6) more. There were no significant differences in any of the measures of use of health care services. INTERPRETATION: This large controlled evaluation of a broadly implemented quality-improvement initiative showed improvement for diabetes process of care and cancer screening outcomes, but not for proxy measures of access related to use of health care services.

Those Left Behind From Voluntary Medical Home Reforms in Ontario, Canada.

PURPOSE: Health systems are transitioning patients to medical homes to improve health outcomes and reduce cost. We sought to understand the characteristics and quality of care for patients who did and did not participate in the voluntary transition to medical homes. METHODS: We used administrative data for diabetes monitoring and cancer screening to compare services received by patients attached to a medical home (n = 10,785,687) with services received by those seeing a fee-for-service physician (n = 1,321,800) in Ontario, Canada, on March 31, 2011. We used Poisson regression to examine associations in 2011 after adjustment for patient factors and also assessed changes in outcomes between 2001 and 2011. RESULTS: Patients attached to a fee-for-service physician were more likely to be immigrants and live in a low-income neighborhood and urban area. They were less likely to receive recommended testing for diabetes (25% vs 34%; adjusted relative risk [RR] = 0.74; 95% CI, 0.73-0.75) and less likely to receive screening for cervical (52% vs 66%; adjusted RR = 0.79; 95% CI, 0.79-0.79), breast (58% vs 73%; adjusted RR = 0.80; 95% CI, 0.80-0.81), and colorectal cancer (44% vs 62%; adjusted RR = 0.72; 95% CI, 0.71-0.72) compared with patients attached to a medical home physician in 2011. These differences in quality of care preceded medical home reforms. CONCLUSION: Patients left behind from medical home reforms are more likely to be poor, urban, and new immigrants and receive lower quality care. Strategies are needed to reach out to these patients and their physicians to reduce gaps in care.

Longitudinal evaluation of physician payment reform and team-based care for chronic disease management and prevention.

BACKGROUND: We evaluated a large-scale transition of primary care physicians to blended capitation models and team-based care in Ontario, Canada, to understand the effect of each type of reform on the management and prevention of chronic disease. METHODS: We used population-based administrative data to assess monitoring of diabetes mellitus and screening for cervical, breast and colorectal cancer among patients belonging to team-based capitation, non-team-based capitation or enhanced fee-for-service medical homes as of Mar. 31, 2011 (n = 10 675 480). We used Poisson regression models to examine these associations for 2011. We then used a fitted nonlinear model to compare changes in outcomes between 2001 and 2011 by type of medical home. RESULTS: In 2011, patients in a team-based capitation setting were more likely than those in an enhanced fee-for-service setting to receive diabetes monitoring (39.7% v. 31.6%, adjusted relative risk [RR] 1.22, 95% confidence interval [CI] 1.18 to 1.25), mammography (76.6% v. 71.5%, adjusted RR 1.06, 95% CI 1.06 to 1.07) and colorectal cancer screening (63.0% v. 60.9%, adjusted RR 1.03, 95% CI 1.02 to 1.04). Over time, patients in medical homes with team-based capitation experienced the greatest improvement in diabetes monitoring (absolute difference in improvement 10.6% [95% CI 7.9% to 13.2%] compared with enhanced fee for service; 6.4% [95% CI 3.8% to 9.1%] compared with non-team-based capitation) and cervical cancer screening (absolute difference in improvement 7.0% [95% CI 5.5% to 8.5%] compared with enhanced fee for service; 5.3% [95% CI 3.8% to 6.8%] compared with non-team-based capitation). For breast and colorectal cancer screening, there were no significant differences in change over time between different types of medical homes. INTERPRETATION: The shift to capitation payment and the addition of team-based care in Ontario were associated with moderate improvements in processes related to diabetes care, but the effects on cancer screening were less clear.

A population-based study of the extent of colorectal cancer screening in men with HIV.

BACKGROUND: Because of the increased life-expectancy of persons with HIV, the need for age-appropriate colorectal cancer screening among these patients will increase. We examined rates of colorectal cancer screening among HIV-infected men aged 50 to 65 years. METHODS: We used Ontario's administrative databases to identify all men between the ages of 50 and 65 years who were alive on April 1, 2007, and identified HIV-infected men using a validated case-finding algorithm. We excluded men with a history of colorectal cancer, anal cancer, inflammatory bowel disease and any colorectal investigation in the preceding five-years, and used multivariable regression to compare rates of colorectal cancer screening between men with and without HIV during five years of follow-up. RESULTS: We identified 743,801 men between the ages of 50 and 65 years, of whom 1,432 (0.19%) were HIV-infected. The proportions of men with and without HIV who underwent any screening during the 5-year follow up period were 49.1% (95% CI 46.5% to 51.7%) and 41.4% (95% CI 41.3% to 41.5%), respectively. Compared with HIV-negative men, men with HIV had lower rates of fecal occult blood testing [adjusted rate ratio (aRR) 0.74; 95% confidence interval (CI) 0.63 to 0.87] and barium-enema radiography (aRR 0.66; 95% CI 0.39 to 1.12), but higher rates of colonoscopy (aRR 1.24; 95% CI 1.13 to 1.37), flexible sigmoidoscopy (aRR 1.72; 95% CI 1.28 to 2.30) and rigid sigmoidoscopy (aRR 2.98; 95% CI 2.26 to 3.93). CONCLUSION: As with the general population of men aged 50 to 65 years, less than half of the population of men with HIV received colorectal cancer screening. Strategies are required to improve uptake of this intervention.

Spatial association between ambient fine particulate matter and incident hypertension.

BACKGROUND: Laboratory studies suggest that exposure to fine particulate matter (≤2.5 µm in diameter) (PM2.5) can trigger a combination of pathophysiological responses that may induce the development of hypertension. However, epidemiological evidence relating PM2.5 and hypertension is sparse. We thus conducted a population-based cohort study to determine whether exposure to ambient PM2.5 is associated with incident hypertension. METHODS AND RESULTS: We assembled a cohort of 35 303 nonhypertensive adults from Ontario, Canada, who responded to 1 of 4 population-based health surveys between 1996 and 2005 and were followed up until December 31, 2010. Incident diagnoses of hypertension were ascertained from the Ontario Hypertension Database, a validated registry of persons diagnosed with hypertension in Ontario (sensitivity=72%, specificity=95%). Estimates of long-term exposure to PM2.5 at participants' postal-code residences were derived from satellite observations. We used Cox proportional hazards models, adjusting for various individual and contextual risk factors including body mass index, smoking, physical activity, and neighbourhood-level unemployment rates. We conducted various sensitivity analyses to assess the robustness of the effect estimate, such as investigating several time windows of exposure and controlling for potential changes in the risk of hypertension over time. Between 1996 and 2010, we identified 8649 incident cases of hypertension and 2296 deaths. For every 10-µg/m(3) increase of PM2.5, the adjusted hazard ratio of incident hypertension was 1.13 (95% confidence interval, 1.05-1.22). Estimated associations were comparable among all sensitivity analyses. CONCLUSIONS: This study supports an association between PM2.5 and incident hypertension.

Herpes zoster as a marker of underlying malignancy.

BACKGROUND: Both herpes zoster and malignancy are associated with immunosuppression. However, the association between herpes zoster and the subsequent diagnosis of malignancy is unclear. We undertook this study to assess whether a diagnosis of herpes zoster is a risk factor for subsequent malignancy. METHODS: For this matched retrospective cohort study, a physician billing database was used to identify individuals 18 years of age or older with a diagnosis of herpes zoster and no prior diagnosis of cancer or HIV infection. Individuals with a herpes zoster diagnosis were matched one-to-one to individuals without a herpes zoster diagnosis, and both groups were examined for up to 5 years for diagnosis of cancer. RESULTS: A total of 542,575 individuals with a diagnosis of herpes zoster were identified. Compared with matched controls, these patients were more likely (p < 0.001) to have a history of myocardial infarction, asthma, congestive heart failure, chronic obstructive pulmonary disease, diabetes mellitus, and hypertension. The incidence of cancer was significantly greater among individuals with herpes zoster than among those without herpes zoster, for both men and women and across all time intervals studied (up to 5 years). The greatest adjusted hazard ratio was seen 180 days after a herpes zoster diagnosis (1.19, 95% confidence interval 1.12-1.25); the hazard ratio decreased as the time from herpes zoster diagnosis increased. Lymphoma was the type of cancer with the greatest relative increase in incidence following diagnosis of herpes zoster. INTERPRETATION: There is a risk of malignancy following an episode of herpes zoster in both men and women and in all age groups 18 years and over. The risk is greatest during the first 180 days following the diagnosis of herpes zoster.

Unintended consequences of delisting routine eye exams on retinopathy screening for people with diabetes in Ontario, Canada.

BACKGROUND: Routine eye examinations for healthy adults aged 20-64 years were delisted from the Ontario Health Insurance Plan in 2004, but they continue to be insured for people with diabetes regardless of age. We sought to assess whether the delisting of routine eye examinations for healthy adults had the unintended consequence of decreasing retinopathy screening for adults with diabetes. METHODS: We used administrative data to calculate eye examinations for people with diabetes ages 40-64 years and 65 years and older in each 2-year period from 1998 to 2010. We examined differences by sex, income, rurality and type of health care provider. We used segmented linear regression to assess the change in trend before and after 2004. RESULTS: For people with diabetes aged 65 years and older, eye examinations rose gradually from 1998 to 2010, with no substantial change between 2004 and 2006. For people with diabetes aged 40-65 years, there was an 8.7% (95% confidence interval [CI] 6.3%-11.1%) decrease in eye examinations between 2004 and 2006. Results were similar for all population subgroups. Ophthalmologic examinations decreased steadily for both age groups during the study period, and there was a decline in optometry examinations for people ages 40-65 years after 2004. INTERPRETATION: The delisting of routine eye examinations for healthy adults in Ontario had the unintended consequence of reducing publicly funded retinopathy screening for people with diabetes. More research is needed to understand whether patients are being charged for an insured service or to what degree misunderstanding has prevented patients from seeking care.