Long-Term Exposure to Low-Level PM2.5 and Mortality: Investigation of Heterogeneity by Harmonizing Analyses in Large Cohort Studies in Canada, United States, and Europe.

BACKGROUND: Studies across the globe generally reported increased mortality risks associated with particulate matter with aerodynamic diameter ≤2.5µm (PM2.5) exposure with large heterogeneity in the magnitude of reported associations and the shape of concentration-response functions (CRFs). We aimed to evaluate the impact of key study design factors (including confounders, applied exposure model, population age, and outcome definition) on PM2.5 effect estimates by harmonizing analyses on three previously published large studies in Canada [Mortality-Air Pollution Associations in Low Exposure Environments (MAPLE), 1991-2016], the United States (Medicare, 2000-2016), and Europe [Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE), 2000-2016] as much as possible. METHODS: We harmonized the study populations to individuals 65+ years of age, applied the same satellite-derived PM2.5 exposure estimates, and selected the same sets of potential confounders and the same outcome. We evaluated whether differences in previously published effect estimates across cohorts were reduced after harmonization among these factors. Additional analyses were conducted to assess the influence of key design features on estimated risks, including adjusted covariates and exposure assessment method. A combined CRF was assessed with meta-analysis based on the extended shape-constrained health impact function (eSCHIF). RESULTS: More than 81 million participants were included, contributing 692 million person-years of follow-up. Hazard ratios and 95% confidence intervals (CIs) for all-cause mortality associated with a 5-µg/m3 increase in PM2.5 were 1.039 (1.032, 1.046) in MAPLE, 1.025 (1.021, 1.029) in Medicare, and 1.041 (1.014, 1.069) in ELAPSE. Applying a harmonized analytical approach marginally reduced difference in the observed associations across the three studies. Magnitude of the association was affected by the adjusted covariates, exposure assessment methodology, age of the population, and marginally by outcome definition. Shape of the CRFs differed across cohorts but generally showed associations down to the lowest observed PM2.5 levels. A common CRF suggested a monotonically increased risk down to the lowest exposure level. https://doi.org/10.1289/EHP12141.

Long-term Exposure to Oxidant Gases and Mortality: Effect Modification by PM 2.5 Transition Metals and Oxidative Potential.

BACKGROUND: Populations are simultaneously exposed to outdoor concentrations of oxidant gases (i.e., O 3 and NO 2 ) and fine particulate air pollution (PM 2.5 ). Since oxidative stress is thought to be an important mechanism explaining air pollution health effects, the adverse health impacts of oxidant gases may be greater in locations where PM 2.5 is more capable of causing oxidative stress. METHODS: We conducted a cohort study of 2 million adults in Canada between 2001 and 2016 living within 10 km of ground-level monitoring sites for outdoor PM 2.5 components and oxidative potential. O x exposures (i.e., the redox-weighted average of O 3 and NO 2 ) were estimated using a combination of chemical transport models, land use regression models, and ground-level data. Cox proportional hazards models were used to estimate associations between 3-year moving average O x and mortality outcomes across strata of transition metals and sulfur in PM 2.5 and three measures of PM 2.5 oxidative potential adjusting for possible confounding factors. RESULTS: Associations between O x and mortality were consistently stronger in regions with elevated PM 2.5 transition metal/sulfur content and oxidative potential. For example, each interquartile increase (6.27 ppb) in O x was associated with a 14.9% (95% CI = 13.0, 16.9) increased risk of nonaccidental mortality in locations with glutathione-related oxidative potential (OP GSH ) above the median whereas a 2.50% (95% CI = 0.600, 4.40) increase was observed in regions with OP GSH levels below the median (interaction P value <0.001). CONCLUSION: Spatial variations in PM 2.5 composition and oxidative potential may contribute to heterogeneity in the observed health impacts of long-term exposures to oxidant gases.

Long-term exposure to wildfires and cancer incidence in Canada: a population-based observational cohort study.

BACKGROUND: Wildfires emit many carcinogenic pollutants that contaminate air, water, terrestrial, and indoor environments. However, little is known about the relationship between exposure to wildfires and cancer risk. We aimed to assess the associations between residential exposure to wildfires and the incidence of several cancer outcomes (lung cancer, brain cancer, non-Hodgkin lymphoma, multiple myeloma, and leukaemia) in Canada. METHODS: We did a population-based observational cohort study of participants in the 1996 Canadian Census Health and Environment Cohort. The 1996 Canadian Census Health and Environment Cohort is a nationally representative sample of Canadian adults, followed up for cancer incidence and mortality from 1996 to 2015. For this analysis, we excluded participants who lived in major Canadian cities (with a population size greater than 1·5 million people), recent immigrants, and individuals younger than 25 years or 90 years of age or older at baseline. Exposures to wildfires were assigned on the basis of area burned within a 20 km or 50 km radius of residential locations and updated for annual residential mobility. Multivariable Cox proportional hazards models were used to estimate associations between exposure to wildfires and specific cancers associated with carcinogenic compounds released by wildfires, including lung and brain cancer, non-Hodgkin lymphoma, multiple myeloma, and leukaemia, adjusted for many personal and neighbourhood-level covariates. FINDINGS: Our analyses included more than 2 million people followed up for a median of 20 years, for a total of 34 million person-years. Wildfire exposure was associated with slightly increased incidence of lung cancer and brain tumours. For example, cohort members exposed to a wildfire within 50 km of residential locations in the past 10 years had a 4·9% relatively higher incidence (adjusted hazard ratio [HR] 1·049, 95% CI 1·028-1·071) of lung cancer than unexposed populations, and a 10% relatively higher incidence (adjusted HR 1·100, 1·026-1·179) of brain tumours. Similar associations were observed for the 20 km buffer size. Wildfires were not associated with haematological cancers in this study, and concentration-response trends were not readily apparent when area burned was modelled as a continuous variable. INTERPRETATION: Long-term exposure to wildfires might increase the risk of lung cancer and brain tumours. Further work is needed to develop long-term estimates of wildfire exposures that capture the complex mixture of environmental pollutants released during these events. FUNDING: Canadian Institute for Health Research and Fonds de recherche du Quebec.

Changes in exposure to ambient fine particulate matter after relocating and long term survival in Canada: quasi-experimental study.

OBJECTIVE: To investigate the association between changes in long term residential exposure to ambient fine particulate matter (PM2.5) and premature mortality in Canada. DESIGN: Population based quasi-experimental study. SETTING: Canada. PARTICIPANTS: 663 100 respondents to the 1996, 2001, and 2006 Canadian censuses aged 25-89 years who had consistently lived in areas with either high or low PM2.5 levels over five years preceding census day and moved during the ensuing five years. INTERVENTIONS: Changes in long term exposure to PM2.5 arising from residential mobility. MAIN OUTCOME MEASURES: The primary outcome was deaths from natural causes. Secondary outcomes were deaths from any cardiometabolic cause, any respiratory cause, and any cancer cause. All outcomes were obtained from the national vital statistics database. RESULTS: Using a propensity score matching technique with numerous personal, socioeconomic, health, and environment related covariates, each participant who moved to a different PM2.5 area was matched with up to three participants who moved within the same PM2.5 area. In the matched groups that moved from high to intermediate or low PM2.5 areas, residential mobility was associated with a decline in annual PM2.5 exposure from 10.6 µg/m3 to 7.4 and 5.0 µg/m3, respectively. Conversely, in the matched groups that moved from low to intermediate or high PM2.5 areas, annual PM2.5 increased from 4.6 µg/m3 to 6.7 and 9.2 µg/m3. Five years after moving, individuals who experienced a reduction in exposure to PM2.5 from high to intermediate levels showed a 6.8% (95% confidence interval 1.7% to 11.7%) reduction in mortality (2510 deaths in 56 025 v 4925 deaths in 101 960). A greater decline in mortality occurred among those exposed to a larger reduction in PM2.5. Increased mortality was found with exposure to PM2.5 from low to high levels, and to a lesser degree from low to intermediate levels. Furthermore, the decreases in PM2.5 exposure were most strongly associated with reductions in cardiometabolic deaths, whereas the increases in PM2.5 exposure were mostly related to respiratory deaths. No strong evidence was found for the changes in PM2.5 exposure with cancer related deaths. CONCLUSIONS: In Canada, decreases in PM2.5 were associated with lower mortality, whereas increases in PM2.5 were associated with higher mortality. These results were observed at PM2.5 levels considerably lower than many other countries, providing support for continuously improving air quality.

Venous thromboembolism after total knee arthroplasty is associated with a worse functional outcome at one year.

AIMS: The primary aim of this study was to assess whether non-fatal postoperative venous thromboembolism (VTE) within six months of surgery influences the knee-specific functional outcome (Oxford Knee Score (OKS)) one year after total knee arthroplasty (TKA). Secondary aims were to assess whether non-fatal postoperative VTE influences generic health and patient satisfaction at this time. METHODS: A study of 2,393 TKAs was performed in 2,393 patients. Patient demographics, comorbidities, OKS, EuroQol five-dimension score (EQ-5D), and Forgotten Joint Score (FJS) were collected preoperatively and one year postoperatively. Overall patient satisfaction with their TKA was assessed at one year. Patients with VTE within six months of surgery were identified retrospectively and compared with those without. RESULTS: A total of 37 patients (1.5%) suffered a VTE and were significantly more likely to have associated comorbidities of stroke (p = 0.026), vascular disease (p = 0.026), and kidney disease (p = 0.026), but less likely to have diabetes (p = 0.046). In an unadjusted analysis, patients suffering a VTE had a significantly worse postoperative OKS (difference in mean (DIM) 4.8 (95% confidence interval (CI) 1.6 to 8.0); p = 0.004) and EQ-5D (DIM 0.146 (95% CI 0.059 to 0.233); p = 0.001) compared with patients without a VTE. After adjusting for confounding variables VTE remained a significant independent predictor associated with a worse postoperative OKS (DIM -5.4 (95% CI -8.4 to -2.4); p < 0.001), and EQ-5D score (DIM-0.169 (95% CI -0.251 to -0.087); p < 0.001). VTE was not independently associated with overall satisfaction after TKA (odds ratio 0.89 (95% CI 0.35 to 2.07); p = 0.717). CONCLUSION: Patients who had a VTE within six months of their TKA had clinically significantly worse knee-specific outcome (OKS) and general health (EQ-5D) scores one year postoperatively, but the overall satisfaction with their TKA was similar to those patients who did not have a VTE. Cite this article: Bone Joint J 2021;103-B(7):1254-1260.

A Population-Based Cohort Study of Respiratory Disease and Long-Term Exposure to Iron and Copper in Fine Particulate Air Pollution and Their Combined Impact on Reactive Oxygen Species Generation in Human Lungs.

Metal components in fine particulate matter (PM2.5) from nontailpipe emissions may play an important role in underlying the adverse respiratory effects of PM2.5. We investigated the associations between long-term exposure to iron (Fe) and copper (Cu) in PM2.5 and their combined impact on reactive oxygen species (ROS) generation in human lungs, and the incidence of asthma, chronic obstructive pulmonary disease (COPD), COPD mortality, pneumonia mortality, and respiratory mortality. We conducted a population-based cohort study of ∼0.8 million adults in Toronto, Canada. Land-use regression models were used to estimate the concentrations of Fe, Cu, and ROS. Outcomes were ascertained using validated health administrative databases. We found positive associations between long-term exposure to Fe, Cu, and ROS and the risks of all five respiratory outcomes. The associations were more robust for COPD, pneumonia mortality, and respiratory mortality than for asthma incidence and COPD mortality. Stronger associations were observed for ROS than for either Fe or Cu. In two-pollutant models, adjustment for nitrogen dioxide somewhat attenuated the associations while adjustment for PM2.5 had little influence. Long-term exposure to Fe and Cu in PM2.5 and estimated ROS concentration in lung fluid was associated with increased incidence of respiratory diseases, suggesting the adverse respiratory effects of nontailpipe emissions.

Fine Particulate Matter Air Pollution and Mortality Risk Among US Cancer Patients and Survivors.

Background: Exposure to fine particulate matter (PM2.5) air pollution has been linked to increased risk of mortality, especially cardiopulmonary and lung cancer mortality. It is unknown if cancer patients and survivors are especially vulnerable to PM2.5 air pollution exposure. This study evaluates PM2.5 exposure and risk for cancer and cardiopulmonary mortality in cohorts of US cancer patients and survivors. Methods: A primary cohort of 5 591 168 of cancer patients and a 5-year survivor cohort of 2 318 068 was constructed using Surveillance, Epidemiology, and End Results Program data from 2000 to 2016, linked with county-level estimates of long-term average concentrations of PM2.5. Cox proportional hazards models were used to estimate PM2.5-mortality hazard ratios controlling for age-sex-race combinations and individual and county-level covariables. Results: Of those who died, 26% died of noncancer causes, mostly from cardiopulmonary disease. Minimal PM2.5-mortality associations were observed for all-cause mortality (hazard ratio [HR] = 1.01, 95% confidence interval [CI] = 1.00 to 1.03) per 10 µg/m3 increase in PM2.5. Substantial adverse PM2.5-mortality associations were observed for cardiovascular (HR = 1.32, 95% CI = 1.26 to 1.39), chronic obstructive pulmonary disease (HR = 1.10, 95% CI = 1.01 to 1.20), influenza and pneumonia (HR = 1.55, 95% CI = 1.33 to 1.80), and cardiopulmonary mortality combined (HR = 1.25, 95% CI = 1.21 to 1.30). PM2.5-cardiopulmonary mortality hazard ratio was higher for cancer patients who received chemotherapy or radiation treatments. Conclusions: Air pollution is adversely associated with cardiopulmonary mortality for cancer patients and survivors, especially those who received chemotherapy or radiation treatment. Given ubiquitous and involuntary air pollution exposures and large numbers of cancer patients and survivors, these results are of substantial clinical and public health importance.

The use of pedobarographic analysis to evaluate movement patterns in unstable total knee arthroplasty: A proof of concept study.

BACKGROUND: Definition and clinical diagnosis of instability in TKA is challenging. Sensitive and objective biomechanical tools to aid diagnosis are currently lacking. This proof-of-concept study evaluates the use of pressure mat analyses to identify abnormal biomechanical loading patterns associated with TKA instability within an outpatient clinical setting. METHODS: Twenty participants were examined: 10 patients with suspected unilateral TKA instability and 10 healthy controls. Participants underwent bilateral stance and gait tests measuring time and limb loading pressure parameters. Gait was divided into three phases: heel strike, mid-foot and toe off. Pressure recordings are expressed relative to bodyweight. Between-limb loading discrepancies were calculated in TKA patients and controls, and these differences were then compared between groups. Statistical significance was accepted at p < 0.05. RESULTS: TKA patients consistentlyoffloadedpressure away from the operated limb, whereas healthy controls exhibited more even limb loading throughout bilateral stance (p < 0.05). TKA patients exhibited greater discrepancy in overall step contact time between limbs (-0.09 s ± 0.16 s; p = 0.016) compared to controls (0.06 s ± 0.08 s; p = 0.04). Post-hoc tests showed significant between-group differences during midfoot (-0.04 s ± 0.07 s; p = 0.03) and toe-off (0.05 s ± 0.14 s; p = 0.013). Between-group differences in limb loading discrepancy were evident at heel strike (-9.24% ± 2.11%; p = 0.0166) and toe-off (-10.34% ± 5.51%; p = 0.0496). DISCUSSION: Pedobarographic measurements demonstrated differences in mechanical loading patterns in patients with TKA instability compared to healthy controls during functional tasks and warrants further investigation. This may prove to be a useful clinical diagnostic tool in identifying patients that would benefit from revision surgery or physical therapy.

Chondrocytes from osteoarthritic cartilage of obese patients show altered adiponectin receptors expression and response to adiponectin.

Obesity and osteoarthritis (OA) are well-known comorbidities and their precise molecular interactions are still unidentified. Adiponectin, a major adipokine, known to have an anti-inflammatory effect in atherosclerosis or Type 2 Diabetes Mellitus (T2DM), has also been postulated to be pro-inflammatory in OA. This dual role of adiponectin is still not explained. The precise mechanism by which adiponectin affects cartilage and chondrocytes remains to be elucidated. In the present observational study chondrocytes from 30 patients with OA (18 females and 12 males) undergoing total knee replacement (TKR) were isolated. Expression of adiponectin receptors 1 and 2 (ADIPOR1 and ADIPOR2) was examined both at gene and protein levels in chondrocytes. The difference in adiponectin receptor expression between lean and obese patients with OA and the role of adiponectin in regulating pro-inflammatory genes (MCP-1, IL-6, and VCAM-1, MMP-1, MMP-2, and TIMP-1) has been investigated. We found that ADIPOR1 represented the most abundant adiponectin receptor in primary OA chondrocytes. ADIPOR1 and ADIPOR2 genes and ADIPOR1 protein were differently expressed in OA chondrocytes obtained from obese compared with lean patients with OA. Adiponectin induced gene expression of MCP-1, IL-6, and MMP-1 in all OA patients' chondrocytes. In contrast, VCAM-1 and MMP-2 were differently regulated by adiponectin depending on the patient's body mass index. This study suggests that adiponectin and ADIPOR1 may have important roles in the pathogenesis of cartilage degeneration in OA of obese subjects.

Long-term exposure to iron and copper in fine particulate air pollution and their combined impact on reactive oxygen species concentration in lung fluid: a population-based cohort study of cardiovascular disease incidence and mortality in Toronto, Canada.

BACKGROUND: Exposure to fine particulate (PM2.5) air pollution is associated with increased cardiovascular disease (CVD), but less is known about its specific components, such as metals originating from non-tailpipe emissions. We investigated the associations of long-term exposure to metal components [iron (Fe) and copper (Cu)] in PM2.5 with CVD incidence. METHODS: We conducted a population-based cohort study in Toronto, Canada. Exposures to Fe and Cu in PM2.5 and their combined impact on the concentration of reactive oxygen species (ROS) in lung fluid were estimated using land use regression models. Incidence of acute myocardial infarction (AMI), congestive heart failure (CHF) and CVD death was ascertained using health administrative datasets. We used mixed-effects Cox regression models to examine the associations between the exposures and health outcomes. A series of sensitivity analyses were conducted, including indirect adjustment for individual-level cardiovascular risk factors (e.g. smoking), and adjustment for PM2.5 and nitrogen dioxide (NO2). RESULTS: In single-pollutant models, we found positive associations between the three exposures and all three outcomes, with the strongest associations detected for the estimated ROS. The associations of AMI and CHF were sensitive to indirect adjustment, but remained robust for CVD death in all sensitivity analyses. In multi-pollutant models, the associations of the three exposures generally remained unaltered. Interestingly, adjustment for ROS did not substantially change the associations between PM2.5 and CVD, but attenuated the associations of NO2. CONCLUSIONS: Long-term exposure to Fe and Cu in PM2.5 and their combined impact on ROS were consistently associated with increased CVD death.

Fine Particulate Matter Exposure and Cancer Incidence: Analysis of SEER Cancer Registry Data from 1992-2016.

BACKGROUND: Previous research has identified an association between fine particulate matter (PM2.5) air pollution and lung cancer. Most of the evidence for this association, however, is based on research using lung cancer mortality, not incidence. Research that examines potential associations between PM2.5 and incidence of non-lung cancers is limited. OBJECTIVES: The primary purpose of this study was to evaluate the association between the incidence of cancer and exposure to PM2.5 using >8.5 million cases of cancer incidences from U.S. registries. Secondary objectives include evaluating the sensitivity of the associations to model selection, spatial control, and latency period as well as estimating the exposure-response relationship for several cancer types. METHODS: Surveillance, Epidemiology, and End Results (SEER) program data were used to calculate incidence rates for various cancer types in 607 U.S. counties. County-level PM2.5 concentrations were estimated using integrated empirical geographic regression models. Flexible semi-nonparametric regression models were used to estimate associations between PM2.5 and cancer incidence for selected cancers while controlling for important county-level covariates. Primary time-independent models using average incidence rates from 1992-2016 and average PM2.5 from 1988-2015 were estimated. In addition, time-varying models using annual incidence rates from 2002-2011 and lagged moving averages of annual estimates for PM2.5 were also estimated. RESULTS: The incidences of all cancer and lung cancer were consistently associated with PM2.5. The incident rate ratios (IRRs), per 10-µg/m3 increase in PM2.5, for all and lung cancer were 1.09 (95% CI: 1.03, 1.14) and 1.19 (95% CI: 1.09, 1.30), respectively. Less robust associations were observed with oral, rectal, liver, skin, breast, and kidney cancers. DISCUSSION: Exposure to PM2.5 air pollution contributes to lung cancer incidence and is potentially associated with non-lung cancer incidence. https://doi.org/10.1289/EHP7246.

Ambient ultrafine particle concentrations and incidence of childhood cancers.

BACKGROUND: Ambient air pollution has been associated with childhood cancer. However, little is known about the possible impact of ambient ultrafine particles (<0.1 µm) (UFPs) on childhood cancer incidence. OBJECTIVE: This study aimed to evaluate the association between prenatal and childhood exposure to UFPs and development of childhood cancer. METHODS: We conducted a population-based cohort study of within-city spatiotemporal variations in ambient UFPs across the City of Toronto, Canada using 653,702 singleton live births occurring between April 1, 1998 and March 31, 2017. Incident cases of 13 subtypes of paediatric cancers among children up to age 14 were ascertained using a cancer registry. Associations between ambient air pollutant concentrations and childhood cancer incidence were estimated using random-effects Cox proportional hazards models. We investigated both single- and multi-pollutant models accounting for co-exposures to PM2.5 and NO2. RESULTS: A total of 1,066 childhood cancers were identified. We found that first trimester exposure to UFPs (Hazard Ratio (HR) per 10,000/cm3 increase = 1.13, 95% CI: 1.03-1.22) was associated with overall cancer incidence diagnosed before 6 years of age after adjusting for PM2.5, NO2, and for personal and neighborhood-level covariates. Association between UFPs and overall cancer incidence exhibited a linear shape. No statistically significant associations were found for specific cancer subtypes. CONCLUSION: Ambient UFPs may represent a previously unrecognized risk factor in the aetiology of cancers in children. Our findings reinforce the importance of conducting further research on the effects of UFPs given their high prevalence of exposure in urban areas.

An ecological analysis of long-term exposure to PM2.5 and incidence of COVID-19 in Canadian health regions.

BACKGROUND: Ambient fine particulate matter (PM2.5) is associated with a wide range of acute and chronic health effects, including increased risk of respiratory infection. However, evidence specifically related to novel coronavirus disease (COVID-19) is limited. METHODS: COVID-19 case counts for 111 Canadian health regions were obtained from the COVID-19 Canada Open Data portal. Annual PM2.5 data for 2000-2016 were estimated from a national exposure surface based on remote sensing, chemical transport modelling and ground observations, and minimum and maximum temperature data for 2000-2015 were based on a national interpolated surface derived from thin-plate smoothing splines. Population counts and sociodemographic data by health region were obtained from the 2016 census, and health data (self-rated health and prevalence of smoking, obesity, and selected chronic diseases) by health region, were obtained from the Canadian Community Health Survey. Data on total number of COVID-19 tests and changes in mobility comparing post-vs. pre-introduction of social distancing measures were available by province. Data were analyzed using negative binomial regression models. RESULTS: After controlling for province, temperature, demographic and health characteristics and days since peak incidence by health region, long-term PM2.5 exposure exhibited a positive association with COVID-19 incidence (incidence rate ratio 1.07, 95% confidence interval 0.97-1.18 per µg/m3). This association was larger in magnitude and statistically significant in analyses excluding provinces that reported cases only for aggregated health regions, excluding health regions with less than median population density, and restricted to the most highly affected provinces (Quebec and Ontario). CONCLUSIONS: We observed a positive association between COVID-19 incidence and long-term PM2.5 exposure in Canadian health regions. The association was larger in magnitude and statistically significant in more highly affected health regions and those with potentially less exposure measurement error. While our results generate hypotheses for further testing, they should be interpreted with caution and require further examination using study designs less prone to bias.

The effect of air pollution on deaths, disease burden, and life expectancy across China and its provinces, 1990-2017: an analysis for the Global Burden of Disease Study 2017.

BACKGROUND: Air pollution is an important public health concern in China, with high levels of exposure to both ambient and household air pollution. To inform action at provincial levels in China, we estimated the exposure to air pollution and its effect on deaths, disease burden, and loss of life expectancy across all provinces in China from 1990 to 2017. METHODS: In all 33 provinces, autonomous regions, municipalities, and special administrative regions in China, we estimated exposure to air pollution, including ambient particulate matter pollution (defined as the annual gridded concentration of PM2·5), household air pollution (defined as the percentage of households using solid cooking fuels and the corresponding exposure to PM2·5), and ozone pollution (defined as average gridded ozone concentrations). We used the methods of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 to estimate deaths and disability-adjusted life-years (DALYs) attributable to air pollution, and what the life expectancy would have been if air pollution levels had been less than the minimum level causing health loss. FINDINGS: The average annual population-weighted PM2·5 exposure in China was 52·7 µg/m3 (95% uncertainty interval [UI] 41·0-62·8) in 2017, which is 9% lower than in 1990 (57·8 µg/m3, 45·0-67·0). We estimated that 1·24 million (95% UI 1·08-1·40) deaths in China were attributable to air pollution in 2017, including 851 660 (712 002-990 271) from ambient PM2·5 pollution, 271 089 (209 882-346 561) from household air pollution from solid fuels, and 178 187 (67 650-286 229) from ambient ozone pollution. The age-standardised DALY rate attributable to air pollution was 1513·1 per 100 000 in China in 2017, and was higher in males (1839·8 per 100 000) than in females (1198·3 per 100 000). The age-standardised death rate attributable to air pollution decreased by 60·6% (55·7-63·7) for China overall between 1990 and 2017, driven by an 85·4% (83·2-87·3) decline in household air pollution and a 12·0% (1·4-22·1) decline in ambient PM2·5 pollution. 40·0% of DALYs for COPD were attributable to air pollution, as were 35·6% of DALYs for lower respiratory infections, 26·1% for diabetes, 25·8% for lung cancer, 19·5% for ischaemic heart disease, and 12·8% for stroke. We estimated that if the air pollution level in China was below the minimum causing health loss, the average life expectancy would have been 1·25 years greater. The DALY rate per 100 000 attributable to air pollution varied across provinces, ranging from 482·3 (371·1-604·1) in Hong Kong to 1725·6 (720·4-2653·1) in Xinjiang for ambient pollution, and from 18·7 (9·1-34·0) in Shanghai to 1804·5 (1339·5-2270·1) in Tibet for household pollution. Although the overall mortality attributable to air pollution decreased in China between 1990 and 2017, 12 provinces showed an increasing trend during the past 27 years. INTERPRETATION: Pollution from ambient PM2·5 and household burning of solid fuels decreased markedly in recent years in China, after extensive efforts to control emissions. However, PM2·5 concentrations still exceed the WHO Air Quality Guideline for the entire population of China, with 81% living in regions exceeding the WHO Interim Target 1, and air pollution remains an important risk factor. Sustainable development policies should be implemented and enforced to reduce the impact of air pollution on long-term economic development and population health. FUNDING: Bill & Melinda Gates Foundation; and China National Key Research and Development Program.

Disease assimilation: The mortality impacts of fine particulate matter on immigrants to Canada.

BACKGROUND: Immigrants make up 20% of the Canadian population; however, little is known about the mortality impacts of fine particulate matter (PM2.5) air pollution on immigrants compared with non-immigrants, or about how impacts may change with duration in Canada. DATA AND METHODS: This study used the 2001 Canadian Census Health and Environment Cohort, a longitudinal cohort of 3.5 million individuals, of which 764,000 were classified as immigrants (foreign-born). Postal codes from annual income tax files were used to account for mobility among respondents and to assign annual PM2.5 concentrations from 1998 to 2016. Exposures were estimated as a three-year moving average prior to the follow-up year. Cox survival models were used to determine hazard ratios (HRs) for cause-specific mortality, comparing the Canadian and foreign-born populations, with further stratification by year of immigration grouped into 10-year cohorts. RESULTS: Differences in urban-rural settlement patterns resulted in greater exposure to PM2.5 for immigrants compared with non-immigrants (mean = 9.3 vs. 7.5 µg/m3), with higher exposures among more recent immigrants. In fully adjusted models, immigrants had higher HRs per 10 µg/m3 increase in PM2.5 concentration compared with Canadian-born individuals for cardiovascular mortality (HR [95% confidence interval] = 1.22 [1.12 to 1.34] vs. 1.12 [1.07 to 1.18]) and cerebrovascular mortality (HR = 1.25 [1.03 to 1.52] vs. 1.03 [0.93 to 1.15]), respectively. However, tests for differences between the two groups were not significant when Cochran's Q test was used. No significant associations were found for respiratory outcomes, except for lung cancer in non-immigrants (HR = 1.10 [1.02 to 1.18]). When stratified by year of immigration, differences in HRs across varied by cause of death. DISCUSSION: In Canada, PM2.5 is an equal-opportunity risk factor, with immigrants experiencing similar if not higher mortality risks compared with non-immigrants for cardiovascular-related causes of death. Some notable differences also existed with cerebrovascular and lung cancer deaths. Continued reductions in air pollution, particularly in urban areas, will improve the health of the Canadian population as a whole.

A finite element analysis of tibial tritanium cones without stems in varying bone defects.

BACKGROUND: In the UK around 10% of hip and knee arthroplasties are revision operations. At revision total knee arthroplasty (rTKA), bone loss management is critical to achieving a stable bone-implant construct. Though tritanium cones have been used to manage bone defects in rTKA, their biomechanical performance with varying defects remains unknown. METHODS: Uncontained tibial bone defects at four anatomic locations, with varying depths and widths (Type T2A and T2B) were investigated computationally in a composite tibia which was subjected to four loading scenarios. The ability of the tritanium cone to replace the tibial bone defect was examined using the outcome measures of bone strain distribution and interface micromotions. RESULTS: It was found that anterior and lateral defects do not significantly alter the strain distribution compared with intact bone. For medial defects, strain distribution is sensitive to defect width; while strain distributions for posterior defects are associated with defect width and depth. In general, micromotions at the bone-implant interface are small and are primarily influenced by defect depth. CONCLUSIONS: Our models show that the cone is an acceptable choice for bone defect management in rTKA. Since all observed micromotions were small, successful osteointegration would be expected in all types of uncontained defects considered in this study. Tritanium cones safely accommodate uncontained tibial defects up to 10 mm deep and extending up to 9 mm from the centre of the cone. Medial and posteriorly based defects managed with symmetric cones display the greatest bone strains and asymmetric cones may be useful in this context.

Cancer mortality risk, fine particulate air pollution, and smoking in a large, representative cohort of US adults.

PURPOSE: Air pollution and smoking are associated with various types of mortality, including cancer. The current study utilizes a publicly accessible, nationally representative cohort to explore relationships between fine particulate matter (PM2.5) exposure, smoking, and cancer mortality. METHODS: National Health Interview Survey and mortality follow-up data were combined to create a study population of 635,539 individuals surveyed from 1987 to 2014. A sub-cohort of 341,665 never-smokers from the full cohort was also created. Individuals were assigned modeled PM2.5 exposure based on average exposure from 1999 to 2015 at residential census tract. Cox Proportional Hazard models were utilized to estimate hazard ratios for cancer-specific mortality controlling for age, sex, race, smoking status, body mass, income, education, marital status, rural versus urban, region, and survey year. RESULTS: The risk of all cancer mortality was adversely associated with PM2.5 (per 10 µg/m3 increase) in the full cohort (hazard ratio [HR] 1.15, 95% confidence interval [CI] 1.08-1.22) and the never-smokers' cohort (HR 1.19, 95% CI 1.06-1.33). PM2.5-morality associations were observed specifically for lung, stomach, colorectal, liver, breast, cervix, and bladder, as well as Hodgkin lymphoma, non-Hodgkin lymphoma, and leukemia. The PM2.5-morality association with lung cancer in never-smokers was statistically significant adjusting for multiple comparisons. Cigarette smoking was statistically associated with mortality for many cancer types. CONCLUSIONS: Exposure to PM2.5 air pollution contributes to lung cancer mortality and may be a risk factor for other cancer types. Cigarette smoking has a larger impact on cancer mortality than PM2.5 , but is associated with similar cancer types.

Reduction in patient outcomes but implant-derived preservation of function following total knee arthroplasty: longitudinal follow-up of a randomized controlled trial.

AIMS: There are comparatively few randomized studies evaluating knee arthroplasty prostheses, and fewer still that report longer-term functional outcomes. The aim of this study was to evaluate mid-term outcomes of an existing implant trial cohort to document changing patient function over time following total knee arthroplasty using longitudinal analytical techniques and to determine whether implant design chosen at time of surgery influenced these outcomes. METHODS: A mid-term follow-up of the remaining 125 patients from a randomized cohort of total knee arthroplasty patients (initially comprising 212 recruited patients), comparing modern (Triathlon) and traditional (Kinemax) prostheses was undertaken. Functional outcomes were assessed with the Oxford Knee Score (OKS), knee range of movement, pain numerical rating scales, lower limb power output, timed functional assessment battery, and satisfaction survey. Data were linked to earlier assessment timepoints, and analyzed by repeated measures analysis of variance (ANOVA) mixed models, incorporating longitudinal change over all assessment timepoints. RESULTS: The mean follow-up of the 125 patients was 8.12 years (7.3 to 9.4). There was a reduction in all assessment parameters relative to earlier assessments. Longitudinal models highlight changes over time in all parameters and demonstrate large effect sizes. Significant between-group differences were seen in measures of knee flexion (medium-effect size), lower limb power output (large-effect size), and report of worst daily pain experienced (large-effect size) favouring the Triathlon group. No longitudinal between-group differences were observed in mean OKS, average daily pain report, or timed performance test. Satisfaction with outcome in surviving patients at eight years was 90.5% (57/63) in the Triathlon group and 82.8% (48/58) in the Kinemax group, with no statistical difference between groups (p = 0.321). CONCLUSION: At a mean 8.12 years, this mid-term follow-up of a randomized controlled trial cohort highlights a general reduction in measures of patient function with patient age and follow-up duration, and a comparative preservation of function based on implant received at time of surgery. Cite this article: Bone Joint J 2020;102-B(4):434-441.

Variation in ligamentous laxity in well-functioning total knee arthroplasty is not associated with clinical outcomes or functional ability.

BACKGROUND: Around 20% of revision knee arthroplasty procedures are carried out for a diagnosis of instability. Clinical evaluation of instability is primarily through physical stress testing of knee ligamentous laxity and joint space opening. It is assumed that increased knee ligament laxity is associated with instability of the knee and, by association, reduced physical function. The range of knee ligament laxity in asymptomatic patients with total knee arthroplasty has however not been reported, nor has the association with measures of physical outcomes. METHODS: Patients who reported being happy with the outcomes of TKA and denied any feelings of knee instability were evaluated at routine follow-up clinicas. Knee ligamentous stability was evaluated seperately by 2 blinded assessors in both coronal and saggital planes. Assessors classified the ligamentous stability as 'tight', 'neutrol' or 'loose'. Clinical outcome was evaluated by Oxford Knee Score, patient satisfaction metric, timed performance test, range of motion and lower limb power. Analysis of variance was employed to evaluate variables between groups with post hoc pairwise comparisons. RESULTS: In total, 42 patients were evaluated. Mean time since index surgery was 46 (SD 8) months. In the coronal plane, 11 (26.2%) were categorised as 'tight', 22 (52.4%) as 'neutral' and 9 (21.4%) as 'loose'. In the sagittal plane, 15 (35.7%) were categorised as 'tight', 17 (40.5%) as 'neutral' and 10 (23.8%) as 'loose'. There were no between-group differences in outcomes: Oxford Knee Score, range of motion, lower limb power, timed functional assessment score or in satisfaction response in either plane (p = 0.05). CONCLUSIONS: We found a range of ligamentous laxity in asymptomatic patients satisfied with the outcome of their knee arthroplasty, and no association between knee laxity and physical ability.

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.