Nationwide Case-crossover Study Research Articles

Low ambient temperature increases the risk and burden of atrial fibrillation episodes: A nationwide case-crossover study in 322 Chinese cities

BackgroundNon-optimum ambient temperature has recently been acknowledged as an independent risk factor for disease burden, but its impact on atrial fibrillation (AF) episodes was rarely evaluated. ObjectivesTo examine the associations between ambient non-optimum temperature and symptom onset of AF episodes and calculate the corresponding disease burden. MethodsWe conducted an individual-level, time-stratified, case-crossover analysis based on a nationwide registry, which comprises of 94,711 eligible AF patients from 1993 hospitals in 322 Chinese cities from January 2015 to December 2021. Multiple moving 24 h average temperatures prior to the symptom onset of AF episodes were calculated as lag days. The associations were analyzed using conditional logistic regression combined with distributed lag non-linear models with a duration of lag 0–7 days, after controlling for criteria air pollutants. Stratification analyses were performed to explore possible effect modifiers. ResultsThere was a monotonically increasing relationship of AF onset risk with decreasing temperature. The excess AF risk occurred at lag 1 d and lasted for 5 days. Nationally, the cumulative relative risk of AF episode onset associated with extremely low temperature (−9.3 °C) over lag 0–7 d was 1.25 (95 % confidence interval: 1.08, 1.45), compared with the reference temperature (31.5 °C). The exposure-response curve was steeper in the south than in the north where there was levelling-off at lower temperature. Nationally, 7.59 % of acute AF episodes could be attributable to non-optimum temperatures. The attributable fraction was larger for southern residents, males and patients <65 years. ConclusionThis nationwide study provides novel and robust evidence that declining ambient temperature could increase the risk of AF episode onset. We also provide the first-hand evidence that a considerable proportion of acute AF episodes could be attributable to non-optimum temperatures.

Heat exposure and hospitalisation for epileptic seizures: A nationwide case-crossover study in Brazil

Climate change is increasing human exposure to heat, especially in tropical regions such as Brazil where temperature reaches up to 40 °C in summer. However, the association between heat exposure and epileptic seizures has not been well demonstrated in Brazil, where lifetime prevalence of epilepsy can range from 11.9/1000 to 21/1000. We collected a total of 225,699 hospitalisation records for epileptic seizures of 1816 municipalities in Brazil, during the hot season from 2000 to 2015, covering nearly 79% of the national population. We implemented a time-stratified case-crossover design combined with distributed lag model with further stratified investigations regarding sex, age, socioeconomic status and region. We found temperature impact threshold was 26 °C in Brazil nationally. Every 1 °C increase from the threshold was associated with an overall 4.3% increased risk of hospitalisation for epileptic seizures on the current day of hospital admission and up to seven days before, which was most pronounced on the second-day exposure to heat. Females, individuals aged 20–30 and persons living in high-income or Southeast regions were more vulnerable. Our results highlight the enhanced risk of heat exposure for epilepsy patients and could contribute to epilepsy management, such as forecasting epileptic seizures. Multi-dimensional adaptive strategies were proposed, covering individual protection, occupational health surveillance, and urban planning management, aiming to reduce heat-induced hospitalisations for epilepsy, and be generalizable to other heat-related diseases.

Application of smart devices in investigating the effects of air pollution on atrial fibrillation onset

Few studies have examined the link between short-term exposure to air pollutants and atrial fibrillation (AF) episodes. This study aims to examine the association of hourly criteria air pollutants with AF episodes. We employ a smart device-based photoplethysmography technology to screen AF from 2018 to 2021. Hourly concentrations of six criteria air pollutants are matched to the onset hour of AF for each participant. We adopt a time-stratified case-crossover design to capture the acute effects of air pollutants on AF episodes, using conditional logistic regression models. Subgroup analyses are conducted by age, gender, and season. A total of 11,906 episodes of AF are identified in 2976 participants from 288 Chinese cities. Generally, the strongest associations of air pollutants are present at lag 18–24 h, with positive and linear exposure-response relationships. For an interquartile range increase in inhalable particles, fine particles, nitrogen dioxide, and carbon monoxide, the odds ratio (OR) of AF is 1.19 [95% confidential interval (CI): 1.03, 1.37], 1.38 (95%CI: 1.14, 1.67), 1.60 (95%CI: 1.16, 2.20) and 1.48 (95%CI: 1.19, 1.84), respectively. The estimates are robust to the adjustment of co-pollutants, and they are larger in females, older people, and in cold seasons. There are insignificant associations for sulfur dioxide and ozone. This nationwide case-crossover study demonstrates robust evidence of significant associations between hourly exposure to air pollutants and the onset of AF episodes, which underscores the importance of ongoing efforts to further improve air quality as an effective target for AF prevention.

Disparities of Heatwave-Related Preterm Birth in Climate Types - China, 2012-2019.

An association between prenatal heatwave exposure and the risk of preterm birth was found. However, the disparities in heatwave-related preterm birth across different climate types have not been examined. This nationwide case-crossover study investigated the association between heatwave exposure and preterm birth across different Köppen-Geiger climate types. Among pregnant women residing in the arid-desert-cold climate type, exposure to compound heatwaves was found to be associated with a significantly higher risk of preterm birth {adjusted odds ratios (AORs) ranged from 1.55 [95% confidence interval ( CI): 1.21-1.97] to 2.11 (95% CI: 1.35-3.31)}. In contrast, among pregnant women residing in the tropical monsoonal climate type, exposure to daytime-only heatwaves was associated with an increased risk of preterm birth [AORs ranged from 1.25 (95% CI: 1.03-1.51) to 1.37 (95% CI: 1.05-1.77)]. Specific interventions should be implemented in China to mitigate the risk of preterm birth related to heatwaves, particularly for pregnant women residing in arid-desert-cold and tropical monsoonal climates.

Criteria air pollutants and hospitalizations of a wide spectrum of cardiovascular diseases: A nationwide case-crossover study in China

Few national studies have systemically examined the effects of criteria air pollutants on cardiovascular morbidity. This study aimed to investigate the associations between all criteria air pollutants and hospitalization of cause-specific cardiovascular diseases (CVD) in China.We obtained data on CVD hospitalization events of four major categories and 12 specific diseases from 153 hospitals distributed in 20 provincial-level regions from 2013 to 2020. We adopted a time-stratified case-crossover study design using individual cases to capture the effect of short-term exposure to six criteria air pollutants on CVD hospitalizations, using conditional logistic regression models. More than 1.1 million CVD hospitalization events were included. The lag pattern exploration demonstrated the largest effect for six air pollutants on lag 0-1 day. PM 2.5 , PM 10 , NO 2 and CO were significantly associated with increased hospitalization from ischemic heart diseases, cerebrovascular diseases, other heart diseases, and five specific causes of CVD. The effect estimates of NO 2 were the most robust when adjusting for co-pollutants. The concentration-response curves were positive and linear for most pollutant-endpoint pairs (except for O 3 ), and these positive associations remained even below the 24-hour levels recommended by WHO Air Quality Guidelines and China Air Quality Standards.This nationwide case-crossover study in China demonstrated that short-term exposure to multiple ambient air pollutants may significantly increase the risk of cause-specific CVD hospitalizations even under the most stringent air quality regulations, striking an alert for potential CVD patients against these environmental risk factors. • A national hospital-based registry for a wide spectrum of CVD hospitalization. • We evaluated the associations of short-term exposure to six criteria air pollutants. • PM 2.5 , PM 10 , NO 2 and CO were significantly associated with increased CVD hospitalization. • Five specific causes of CVDs were closely linked with exposure to air pollution. • We observed adverse effects of air pollution below the recent WHO Air Quality Guidelines.

Ambient heat exposure and COPD hospitalisations in England: A nationwide case-crossover study during 2007-2018

Ambient heat exposure and COPD hospitalisations in England: A nationwide case-crossover study during 2007-2018

Low ambient temperature might trigger the symptom onset of pulmonary embolism: A nationwide case-crossover study at hourly level in China

BackgroundPulmonary embolism (PE) is an important cause of death and its seasonality has long been observed. Very few epidemiological studies have explored the potential role of ambient temperature in PE symptom onset, especially at the hourly level. MethodsWe conducted a time-stratified case-crossover study among 17,903 PE patients with hourly onset of symptom from 1590 hospitals across China between January 2015 and September 2020. Conditional logistic regression model combined with distributed lag non-linear models were used to explore the associations between hourly ambient temperature and PE symptom onset. The attributable fractions due to non-optimum temperature were calculated. ResultsThe exposure-response relationship curve was inverse and almost linear. Lower temperature was significantly associated with higher risk of PE symptom onset when temperature was below 18 °C. This risk occurred immediately at the same hour, attenuated thereafter, and became nonsignificant at approximately 72 h after exposure. Compared with the referent temperature (P99, 34.1 °C), the odds ratio of PE symptom onset associated with extremely low temperature (P1, −16.1 °C) over lag 0–72 h was 1.63 (95%CI: 1.23, 2.16). Low temperature may account for 16.19 % of the symptom onset nationally with higher proportion in the south of China. The effects were stronger in older adults, males, and cold seasons. ConclusionsWe provided the first-hand robust evidence that transient exposure (at the hourly level) to low temperature might trigger the symptom onset of PE and constitute a considerable burden for PE patients. Targeted protections and health education are needed for susceptible populations.

High ambient temperature and risk of hospitalization for gastrointestinal infection in Brazil: A nationwide case-crossover study during 2000–2015

BackgroundThe burden of gastrointestinal infections related to hot ambient temperature remains largely unexplored in low-to-middle income countries which have most of the cases globally and are experiencing the greatest impact from climate change. The situation is particularly true in Brazil. ObjectivesUsing medical records covering over 78 % of population, we quantify the association between high temperature and risk of hospitalization for gastrointestinal infection in Brazil between 2000 and 2015. MethodsData on hospitalization for gastrointestinal infection and weather conditions were collected from 1814 Brazilian cities during the 2000–2015 hot seasons. A time-stratified case-crossover design was used to estimate the association. Stratified analyses were performed by region, sex, age-group, type of infection and early/late study period. ResultsFor every 5 °C increase in mean daily temperature, the cumulative odds ratio (OR) of hospitalization over 0–9 days was 1.22 [95 % confidence interval (CI): 1.21, 1.23] at the national level, reaching its maximum in the south and its minimum in the north. The strength of association tended to decline across successive age-groups, with infants < 1 year most susceptible. The effect estimates were similar for men and women. Waterborne and foodborne infections were more associated with high temperature than the ‘others’ and ‘idiopathic’ groups. There was no substantial change in the association over the 16-year study period. DiscussionOur findings indicate that exposure to high temperature is associated with increased risk of hospitalization for gastrointestinal infection in the hot season, with the strength varying by region, population subgroup and infection type. There was no evidence to indicate adaptation to heat over the study duration.

Non-optimum temperature increases risk and burden of acute myocardial infarction onset: A nationwide case-crossover study at hourly level in 324 Chinese cities.

SummaryBackgroundThe associations of ambient temperature with acute myocardial infarction (AMI) have seldom been examined based on the time of symptom onset.MethodsWe conducted a time-stratified case-crossover study among 1,046,773 eligible AMI patients from 2,093 hospitals in 324 Chinese cities from January 1, 2015 to June 30, 2021, after excluding those transferred from other hospitals or having not reported the time of symptom onset. Hourly exposure to ambient temperature was calculated as multiple moving 24-h averages (days) before hourly onset of AMI symptoms. Conditional logistic regression and distributed lag non-linear models with a duration of 0–21 days were used to estimate the cumulative associations of non-optimum temperature with AMI onset and the corresponding disease burden nationally. Subgroup analyses by region and period were conducted. Specifically, cities with and without centralized heating system were classified into heating and non-heating regions, respectively. The whole year in heating region was divided into heating and non-heating periods based on the duration of centralized heating in each city.FindingsAlmost monotonically increasing risks were observed for both overall AMI and its two subtypes when ambient temperature declined. The effects of extremely low temperature occurred immediately on the concurrent day, and lasted up to almost 3 weeks. The excess risks of AMI onset associated with non-optimum ambient temperatures were observed during the whole year in the non-heating region and non-heating period in the heating region, but not during heating period. Specifically, odds ratios of AMI onset associated with extremely low temperature cumulated over 0–21 days were 1.24 (95% CI: 1.13–1.37), 1.46 (95% CI: 1.20–1.76), and 1.62 (95% CI: 1.46–1.81) in the heating region during non-heating period, in the non-heating region during winter and non-winter period, respectively. The heat effects on AMI onset were very modest and transient. Totally, 13.26% of AMI cases could be attributable to non-optimum temperatures nationally. The burden of AMI attributable to non-optimum temperature was much smaller in heating region than in non-heating region. Somewhat stronger effects were observed in females and patients aged older than 65.InterpretationThis nationwide study provided robust evidence that non-optimum ambient temperature may significantly trigger AMI onset, and for the first time estimated the disease burden after accounting for spatial and seasonal heterogeneity. Centralized heating might substantially mitigate AMI burden due to non-optimum temperature.FundingShanghai International Science and Technology Partnership Project, National Natural Science Foundation of China, Talent Training Program of Zhongshan Hospital, Fudan University.

Ambient heat exposure and COPD hospitalisations in England: a nationwide case-crossover study during 2007–2018

BackgroundThere is emerging evidence suggesting a link between ambient heat exposure and chronic obstructive pulmonary disease (COPD) hospitalisations. Individual and contextual characteristics can affect population vulnerabilities to COPD hospitalisation due...

Association of benzodiazepines, Z-drugs, pregabalin, and melatonin with traffic accidents: A nationwide cohort and case-crossover study in Danish adults.

Benzodiazepines, Z-drugs, pregabalin, and melatonin (BZPMs) have been associated with a higher risk of traffic accidents, but the evidence is inconsistent, and lacking for newer drugs. To examine the association of BZPMs with risk of traffic accidents. All Danish adults (n = 3,823,588) were followed for redeemed prescriptions of BZPM and for incident traffic accidents registered in Danish registers from 2002 through 2018. Associations were examined in cohort and case-crossover designs using Cox proportional hazard and conditional logistic regression with adjustment for co-variables. A total of 19.3% (n = 738,019) of all participants initiated treatment with BZPMs. During the mean follow-up of 10.3 years, 595,173(15.5%) of participants were involved in a traffic accident. In the cohort analysis, all BZPMs besides pregabalin were associated with a higher risk of traffic accidents in adults below 70 years, with chlordiazepoxide showing the strongest association (hazard ratio (HR)age 18-49 = 1.76, 95% confidence interval (CI): 1.67-1.86 and HRage 50-69 = 1.84, 95% CI: 1.70-2.00). In the older age groups, the specific BZPM medications were associated with lower or no risk of traffic accidents. However, in case-time-crossover analysis with inherited control for confounders, no BZPM medication was positively associated with traffic accidents, except for chlordiazepoxide, which had a higher odds ratio in middle-aged group (1.62, 95% CI: 1.15-2.29). This study does not fully support that BZPM use is a risk factor for traffic accidents. However, a positive association was found for chlordiazepoxide, which is approved for treatment of acute alcohol withdrawal.

Fine particulate matter air pollution and under-5 children mortality in China: A national time-stratified case-crossover study.

Under-5 mortality rate is an important indicator in Millennium Development Goals and Sustainable Development Goals. To date, no nationally representative studies have examined the effects of fine particulate matter (PM2.5) air pollution on under-5 mortality. To investigate the association of short-term exposure to PM2.5 with under-5 mortality from total and specific causes in China. We used the national Maternal and Child Health Surveillance System to identify under-5 mortality cases during the study period of 2009 to 2019. We adopted a time-stratified case-crossover study design at the individual level to capture the effect of short-term exposure to daily PM2.5 on under-5 mortality, using conditional logistic regression models. A total of 61,464 under-5 mortality cases were included. A 10μg/m3 increase in concentrations of PM2.5 on lag 0-1 d was significantly associated with a 1.15% (95%confidence interval: 0.65%, 1.65%) increase in under-5 mortality. Mortality from diarrhea, pneumonia, digestive diseases, and preterm birth were significantly associated with exposure to PM2.5. The effect estimates were larger for neonatal mortality (<28days), female children, and in warm seasons. We observed steeper slopes in lower ranges (<50μg/m3) of the concentration-response curve between PM2.5 and under-5 mortality, and positive associations remained below the 24-h PM2.5 concentration limit recommended by WHO Air Quality Guidelines and China Air Quality Standards. This nationwide case-crossover study in China demonstrated that acute exposure to PM2.5 may significantly increase the risk of under-5 mortality, with larger effects for neonates, female children, and during warm seasons. Relevant control strategies are needed to remove this roadblock to achieving under-5 mortality targets in developing countries.

Association between ambient temperature and hospitalization for renal diseases in Brazil during 2000–2015: A nationwide case-crossover study

Climate change is increasing the risks of injuries, diseases, and deaths globally. However, the association between ambient temperature and renal diseases has not been fully characterized. This study aimed to quantify the risk and attributable burden for hospitalizations of renal diseases related to ambient temperature. Daily hospital admission data from 1816 cities in Brazil were collected during 2000 and 2015. A time-stratified case-crossover design was applied to evaluate the association between temperature and renal diseases. Relative risks (RRs), attributable fractions (AFs), and their confidence intervals (CIs) were calculated to estimate the associations and attributable burden. A total of 2,726,886 hospitalizations for renal diseases were recorded during the study period. For every 1°C increase in daily mean temperature, the estimated risk of hospitalization for renal diseases over lag 0-7 days increased by 0·9% (RR=1·009, 95% CI: 1·008-1·010) at the national level. The associations between temperature and renal diseases were largest at lag 0 days but remained for lag 1-2 days. The risk was more prominent in females, children aged 0-4 years, and the elderly ≥ 80 years. 7·4% (95% CI: 5·2-9·6%) of hospitalizations for renal diseases could be attributable to the increase of temperature, equating to 202,093 (95% CI: 141,554-260,594) cases. This nationwide study provides robust evidence that more policies should be developed to prevent heat-related hospitalizations and mitigate climate change. China Scholarship Council, and the Australian National Health and Medical Research Council.

Socioeconomic level and associations between heat exposure and all-cause and cause-specific hospitalization in 1,814 Brazilian cities: A nationwide case-crossover study

BACKGROUND AND AIM: Little is known about socioeconomic disparities in vulnerability to heat. We aimed to evaluate whether there were socioeconomic disparities in vulnerability to heat-related all-cause and cause-specific hospitalization among Brazilian cities. METHODS: We collected daily hospitalization and weather data in the hot season (city-specific 4 adjacent hottest months each year) during 2000–2015 from 1,814 Brazilian cities covering 78.4% of the Brazilian population. A time-stratified case-crossover design modeled by quasi-Poisson regression and a distributed lag model was used to estimate city-specific heat–hospitalization association. Then meta-analysis was used to synthesize city-specific effect estimates according to different socioeconomic quartiles or levels. RESULTS:We included 49 million hospitalizations (58.5% female; median [interquartile range] age: 33.3 [19.8–55.7] years). For cities of lower middle income (LMI), upper middle income (UMI), and high income (HI) according to the World Bank’s classification, every 5°C increase in daily mean temperature during the hot season was associated with a 5.1% (95% CI 4.4%–5.7%,), 3.7% (3.3%–4.0%), and 2.6% (1.7%–3.4%) increase in all-cause hospitalization, respectively. The inter-city socioeconomic disparities in the association were strongest for children and adolescents (0–19 years) (effect estimates: 9.9% in LMI cities vs 5.2% in HI cities). The disparities were particularly evident for hospitalization due to certain diseases, including ischemic heart disease (effect estimates: 5.6% in LMI cities vs 0.5% in HI cities), asthma (3.7% vs −6.4%), pneumonia (8.0% vs 3.8%), renal diseases (9.6% vs 4.9%), mental health conditions (17.2% vs 5.5%), and neoplasms (3.1% vs −0.1%). The disparities were similar when stratifying the cities by other socioeconomic indicators (urbanization rate, literacy rate, and household income). CONCLUSIONS:Less developed cities displayed stronger associations between heat exposure and all-cause hospitalizations and certain types of cause-specific hospitalizations in Brazil. This may exacerbate the existing geographical health and socioeconomic inequalities under a changing climate. KEYWORDS: Temperature, Socio-economic factors (non-chemical stressors), Environmental disparities, Environmental justice, Big data

Temperature variability and asthma hospitalisation in Brazil, 2000–2015: a nationwide case-crossover study

BackgroundBoth cold and hot temperature have been associated with the onset of asthma, but it remains largely unknown about the risk of asthma hospitalisation associated with short-term temperature fluctuation or...

Socioeconomic level and associations between heat exposure and all-cause and cause-specific hospitalization in 1,814 Brazilian cities: Anationwide case-crossover study.

Heat exposure, which will increase with global warming, has been linked to increased risk of a range of types of cause-specific hospitalizations. However, little is known about socioeconomic disparities in vulnerability to heat. We aimed to evaluate whether there were socioeconomic disparities in vulnerability to heat-related all-cause and cause-specific hospitalization among Brazilian cities. We collected daily hospitalization and weather data in the hot season (city-specific 4 adjacent hottest months each year) during 2000-2015 from 1,814 Brazilian cities covering 78.4% of the Brazilian population. A time-stratified case-crossover design modeled by quasi-Poisson regression and a distributed lag model was used to estimate city-specific heat-hospitalization association. Then meta-analysis was used to synthesize city-specific estimates according to different socioeconomic quartiles or levels. We included 49 million hospitalizations (58.5% female; median [interquartile range] age: 33.3 [19.8-55.7] years). For cities of lower middle income (LMI), upper middle income (UMI), and high income (HI) according to the World Bank's classification, every 5°C increase in daily mean temperature during the hot season was associated with a 5.1% (95% CI 4.4%-5.7%, P < 0.001), 3.7% (3.3%-4.0%, P < 0.001), and 2.6% (1.7%-3.4%, P < 0.001) increase in all-cause hospitalization, respectively. The inter-city socioeconomic disparities in the association were strongest for children and adolescents (0-19 years) (increased all-cause hospitalization risk with every 5°C increase [95% CI]: 9.9% [8.7%-11.1%], P < 0.001, in LMI cities versus 5.2% [4.1%-6.3%], P < 0.001, in HI cities). The disparities were particularly evident for hospitalization due to certain diseases, including ischemic heart disease (increase in cause-specific hospitalization risk with every 5°C increase [95% CI]: 5.6% [-0.2% to 11.8%], P = 0.060, in LMI cities versus 0.5% [-2.1% to 3.1%], P = 0.717, in HI cities), asthma (3.7% [0.3%-7.1%], P = 0.031, versus -6.4% [-12.1% to -0.3%], P = 0.041), pneumonia (8.0% [5.6%-10.4%], P < 0.001, versus 3.8% [1.1%-6.5%], P = 0.005), renal diseases (9.6% [6.2%-13.1%], P < 0.001, versus 4.9% [1.8%-8.0%], P = 0.002), mental health conditions (17.2% [8.4%-26.8%], P < 0.001, versus 5.5% [-1.4% to 13.0%], P = 0.121), and neoplasms (3.1% [0.7%-5.5%], P = 0.011, versus -0.1% [-2.1% to 2.0%], P = 0.939). The disparities were similar when stratifying the cities by other socioeconomic indicators (urbanization rate, literacy rate, and household income). The main limitations were lack of data on personal exposure to temperature, and that our city-level analysis did not assess intra-city or individual-level socioeconomic disparities and could not exclude confounding effects of some unmeasured variables. Less developed cities displayed stronger associations between heat exposure and all-cause hospitalizations and certain types of cause-specific hospitalizations in Brazil. This may exacerbate the existing geographical health and socioeconomic inequalities under a changing climate.

Fracture risk increased by concurrent use of central nervous system agents in older people: Nationwide case-crossover study.

Multiple medication use among older patients is reported to increase fracture risk. But this association is unclear in different subgroups and has not been confirmed by a case-crossover study, which can eliminate measurable and unmeasurable time-invariant confounders. To estimate the fragility fracture risk associated with concurrent use of multiple central nervous system (CNS) agents in older patients using a case-crossover design. This study targeted almost all patients aged ≥65 years in Japan who incurred fragility fractures from May 2013 to September 2014, based on the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB Japan). Conditional logistic regression analysis estimated the risk of fragility fracture associated with the daily number of CNS agents, including subgroup analyses stratified by sex, age, and fracture location. For 446,101 patients, the adjusted odds ratios (ORs) of fragility fracture increased almost linearly with number of CNS agents; 0, 0-1, 1-2, 2-3, 3-4, 4-5, and >5: OR reference, 1.21 (95% confidence interval, 1.18-1.23), 1.40 (1.35-1.46), 1.58 (1.49-1.67), 1.89 (1.74-2.05), 1.80 (1.60-2.03), and 1.90 (1.61-2.23; trend p<0.001), respectively. A similar trend was observed for several subgroups, especially in males and those aged ≥85 years, showing marked linearity. The increased risk of fragility fracture associated with the use of multiple CNS agents was robust in older people in Japan.

Antithrombotic medication and endovascular interventions associated with short-term exposure to particulate air pollution: A nationwide case-crossover study

Short-term exposure to air pollution has pro-thrombotic effects and triggers thrombo-embolic events such as myocardial infarction or stroke in adults. This study evaluates the association between short-term variation in air pollution and treatments for acute thrombo-embolic events among the whole Belgian population. In a bidirectional time-stratified case-crossover design, we included 227,861 events treated with endovascular intervention and 74,942 with antithrombotic enzymes that were reimbursed by the Belgian Social Security between January 1st, 2009 and December 31st, 2013. We compared the concentrations of particulate matter (PM) air pollution (PM10 and PM2.5), as estimated at the municipality level on the day of the event (lag 0) and two days earlier (lag 1 and lag 2) with those of control days from the same month, matched by temperature and accounting for day of the week (weekend vs week days). We applied conditional logistic regression models to obtain odds ratios (OR) and their 95% CI for an increase of 10 μg/m3 (PM10) or 5 μg/m3 (PM2.5) in pollutant concentrations over three lag days (lag 0, 1 and 2). We observed significant associations of PM10 and PM2.5 with treatment of acute thrombo-embolic events at the three lags. The strongest associations were observed for air pollution concentrations on the day of the event (lag0). Increases of 10 μg/m3 PM10 and 5 μg/m3 PM2.5 on lag0 increased the odds of events treated with endovascular intervention by 2.7% (95%CI:2.3%–3.2%) and 1.3% (95%CI:1%–1.5%), respectively, and they increased the odds of events treated with antithrombotic enzymes by 1.9% (95%CI:1.1–2.7%) and 1.2% (95%CI:0.7%–1.6%), respectively. The associations were generally stronger during autumn months and among children. Our nationwide study confirms that acute exposure to outdoor air pollutants such as PM10 or PM2.5 increase the use of medication and interventions to treat thrombo-embolic events.

Risk of stroke associated with intravitreal ranibizumab injections in age-related macular degeneration: a nationwide case-crossover study.

To evaluate the risk of stroke associated with intravitreal ranibizumab in age-related macular degeneration (AMD). A nationwide retrospective case-crossover study was performed using data from the Korean National Health Insurance Service (KNHIS) database, which included patients with exudative AMD in South Korea (n = 41,860). The index date was the date of hospitalization for stroke. We defined the case period as 60 days and four control periods before the index date. A pharmacy prescription database was searched for ranibizumab use during the case and control periods. We calculated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) with a conditional logistic regression model. A total of 865 patients with AMD and incident stroke were included. Of all the patients, 12.02% had been treated during the preceding 60-day case period, compared with 9.25-10.29% during control periods. The adjusted OR of stroke associated with intravitreal ranibizumab during the case period was 1.285 (95% CI 0.979-1.686) (p = 0.07). In the subgroup analysis, the risk of hemorrhagic stroke had an OR of 2.252 (95% CI 1.068-4.749, p = 0.033). Further analyses based on patient gender, age, and different risk periods of 15 and 30 days yielded no increase in the risk of stroke associated with intravitreal ranibizumab. This case-crossover analysis revealed no evidence of increased risk of hospitalization for stroke within 60 days of intravitreal ranibizumab injection in AMD patients. A secondary analysis indicated the possibility of an increased risk of hemorrhagic stroke, with borderline significance. Further research is needed regarding the underlying biological mechanisms and drug safety.

Short-term exposure to ambient fine particulate matter and out-of-hospital cardiac arrest: a nationwide case-crossover study in Japan

PM2·5 is an important but modifiable environmental risk factor, not only for pulmonary diseases and cancers, but for cardiovascular health. However, the evidence regarding the association between air pollution and acute cardiac events, such as out-of-hospital cardiac arrest (OHCA), is inconsistent, especially at concentrations lower than the WHO daily guideline (25 μg/m3). This study aimed to determine the associations between exposure to ambient air pollution and the incidence of OHCA. In this nationwide case-crossover study, we linked prospectively collected population-based registry data for OHCA in Japan from Jan 1, 2014, to Dec 31, 2015, with daily PM2·5, carbon monoxide (CO), nitrogen dioxide (NO2), photochemical oxidants (Ox), and sulphur dioxide (SO2) exposure on the day of the arrest (lag 0) or 1-3 days before the arrest (lags 1-3), as well as the moving average across days 0-1 and days 0-3. Daily exposure was calculated by averaging the measurements from all PM2·5 monitoring stations in the same prefecture. The effect of PM2·5 on risk of all-cause or cardiac OHCA was estimated using a time-stratified case-crossover design coupled with conditional logistic regression analysis, adjusted for daily temperature and relative humidity. Single-pollutant models were also investigated for the individual gaseous pollutants (CO, NO2, Ox, and SO2), as well as two-pollutant models for PM2·5 with these gaseous pollutants. Subgroup analyses were done by sex and age. Over the 2 years, 249 372 OHCAs were identified, with 149 838 (60·1%) presumed of cardiac origin. The median daily PM2·5 was 11·98 μg/m3 (IQR 8·13-17·44). Each 10 μg/m3 increase in PM2·5 was associated with increased risk of all-cause OHCA on the same day (odds ratio [OR] 1·016, 95% CI 1·009-1·023) and at lags of up to 3 days, ranging from OR 1·015 (1·008-1·022) at lag 1 to 1·033 (1·023-1·043) at lag 0-3. Results for cardiac OHCA were similar (ORs ranging from 1·016 [1·007-1·025] at lags 1 and 2 to 1·034 [1·021-1·047] at lag 0-3). Patients older than 65 years were more susceptible to PM2·5 exposure than younger age groups but no sex differences were identified. CO, Ox, and SO2 were also positively associated with OHCA while NO2 was not. However, in two-pollutant models of PM2·5 and gaseous pollutants, only PM2·5 (positive association) and NO2 (negative association) were independently associated with increased risk of OHCA. Short-term exposure to PM2·5 was associated with an increased risk of OHCA even at relatively low concentrations. Regulatory standards and targets need to incorporate the potential health gains from continual air quality improvement even in locations already meeting WHO standards. None.