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• The last decade witnessed a rapid increase in epilepsy mortality. • Mortality from epilepsy was higher in Black individuals and men. • Similar upward trends in the last decade have been observed across ages, genders, and ethnicities. • A comprehensive assessment of long-term trends in mortality from epilepsy holds significance for healthcare prioritization. The analysis of long-term trends of mortality from epilepsy has not been conducted, which is crucial for estimating the future burden of epilepsy. We therefore aimed to investigate the long-term trends of mortality from epilepsy in the United States from 1979 to 2021. The cause-of-death and demographic data were from the National Center for Health Statistics (1979–2021) and population estimates were from the US Census Bureau. We used the joinpoint regression model to analyze secular trends in the mortality of epilepsy spanning from 1979 to 2021. Age-adjusted mortality from epilepsy was assessed based on the year 2000 U.S. population data, stratified by age, sex, and race. The age-adjusted mortality from epilepsy increased from 0.78 per 100,000 population in 1979 to 1.01 per 100,000 population in 2021, with an average annual percent change (AAPC) of 0.58% (95% confidence interval [CI]: 0.45% - 0.72%). The overall age-adjusted mortality of epilepsy had been on the rise between 2011 and 2021. The mortality rate generally increases with age. The mortality of epilepsy was higher in the Afro-American people and men. The mortality of epilepsy in both sexes declined first and then increased, with AAPC 1.02% (95% CI: 0.88%, 1.23%) in women and 0.10% (95% CI: -0.002%, 0.21%) in men. Mortality in all races including White, Afro-American people, and other races individuals fell first and then rose. The AAPC of mortality in White, other races, and Afro-American people were 0.89% (95% CI: 0.79%, 1.02%), -0.87% (95% CI: -1.84%, 0.88%), and -0.31% (95% CI: -0.48%, -0.13%), respectively. Although the mortality rate from epilepsy has experienced a period of decline, it is worth noting that the last decade has seen a rapid increase. A comprehensive assessment of long-term trends in mortality from epilepsy holds significance for healthcare prioritization. [ABSTRACT FROM AUTHOR]

Alarming levels of emotional symptoms among youth were reported during the COVID-19 pandemic. Studies assessing these figures against the pre-pandemic developments are rare. We examined the trend of generalized anxiety (GA) in adolescents in the 2010s and the effect of the COVID-19 pandemic against this trend. Data from the Finnish School Health Promotion study with 750,000 participants aged 13–20 between 2013 and 2021 was analyzed using GAD-7 to measure self-reported GA (cut-off ≥10). Inquiries were made about remote learning arrangements. Effects of time and COVID-19 were analyzed with logistic regression. Among females, an increasing trend in GA between 2013 and 2019 was found (OR per year 1.05), and the prevalence increased from 15.5 % to 19.7 %. Among males, the trend was decreasing (OR = 0.98), with prevalence from 6.0 % to 5.5 %. Increase in GA from 2019 to 2021 was stronger in females (19.7 % to 30.2 %) than males (5.5 % to 7.8 %), while the effect of COVID-19 on GA was equally strong (OR = 1.59 vs. OR = 1.60) against the pre-pandemic trends. Remote learning was associated with elevated levels of GA, especially among those with unmet needs for learning support. The design of repeated cross-sectional surveys doesn't allow analyses of within individual changes. Given the pre-pandemic trends of GA, the COVID-19 effect on it appeared equal in both sexes. The increasing pre-pandemic trend among adolescent females and the strong effect of COVID-19 on GA among both sexes warrants constant monitoring of mental health of the youth in the aftermath of the COVID-19 pandemic. • Prevalence of generalized anxiety (GA) increased among females during the 2010s. • Among males the trend in GA was almost flat, while slightly decreasing. • Against these trends, the effect of COVID-19 on GA in adolescents was very strong. • Considering the trends the effect of COVID-19 was equally strong for both sexes. • Monitoring adolescent mental health is warranted during the post-COVID-19 era. [ABSTRACT FROM AUTHOR]

Evaluating carbon footprint pressure (CFP) scientifically and quantifying the environmental impact of economic activities precisely are crucial for informing policies on carbon emission reduction and achieving carbon neutrality in China. This study revealed China's CFP from 2005 to 2021 using data sets of fossil fuel carbon emissions and vegetation carbon sequestration from remote sensing. We investigated the drivers of CFP using LMDI decomposition. Additionally, we used the Tapio model to examine the decoupling of CFP and economic growth. The findings indicate that China's CFP has increased over time and shows a positive spatial correlation. Rapid economic growth and significant population expansion are the primary drivers of the surge in CFP. Conversely, optimizing energy structure, reducing energy intensity, and enhancing ecological quality are key to alleviating the rising pressure on China's carbon footprint. Moreover, we observe a weak decoupling of China's CFP and economic growth. Notably, it is more challenging to achieve an ideal decoupling state in the western region than in the central and eastern regions. • We constructed the CFP index based on remote sensing data. • China's CFP has shown an upward trend over time. • Provincial CFP has positively correlated spatial agglomeration characteristics. • GDP and population size are the main reasons for China's CFP increase. • China's CFP and GDP generally show a weak decoupling state. [ABSTRACT FROM AUTHOR]

Objective: To examine time trends in the use of NSAIDs and opioids for patients with osteoarthritis undergoing total hip arthroplasty (THA) during 1996-2018.Method: Using Danish population-based medical databases, we identified 103,209 THA patients. Prevalence rates of NSAID and opioid use among preoperative users and non-users were calculated in four quarters (Q1-Q4) after THA by calendar periods (1996-2000, 2001-2006, 2007-2012 and 2013-2018). Prevalence rate ratios (PRR) were adjusted for age and gender.Results: Among preoperative NSAID users and non-users, NSAID use in Q1 increased from 32.6% in 1996-2000 to 48.0% in 2013-2018 (PRR = 1.49, 95% CI: 1.42-1.55) and from 12.9% to 32.0% (PRR = 2.49 (2.32-2.67)), respectively. Among preoperative opioid users and non-users, opioid use in Q1 increased from 42.7% in 1996-2000 to 76.9% in 2013-2018 (PRR = 1.81 (1.73-1.89)) and from 15.2% to 58.2% (PRR = 3.85 (3.65-4.05)), respectively. NSAID use in Q4 decreased from 24.5% in 1996-2000 to 21.4% in 2013-2018 (PRR = 0.88 (0.83-0.93)) and from 6.9% to 5.6% (PRR = 0.81 (0.73-0.91)) in preoperative NSAIDs users and non-users, respectively. Opioid use in Q4 increased from 26.6% in 1996-2000 to 28.6% (PRR = 1.08 (1.02-1.15)) in 2013-2018 and from 4.1% to 5.0% (PRR = 1.25 (1.11-1.40)) in preoperative opioid users and non-users, respectively.Conclusion: We observed up to a 4-fold increase in NSAID and opioid use in Q1 during 1996-2018, while usage in Q4 did not change substantially. However, 5-6% of the preoperative non-users of NSAIDs and opioids were users in Q4, which might relate to inaccurate indication for or timing of THA and the post-surgical phasing out of analgesics use. [ABSTRACT FROM AUTHOR]

Age-sex specific trend analyses of ischemic heart disease (IHD)-related mortality and prevalent risk factors can improve our understanding and approach to the disease. We performed a 15-year retrospective epidemiological analysis of acute and chronic IHD-related mortality and prevalent cardiovascular risk factors using administrative data from Veneto, a socio-economically homogeneous Italian region. Standard mortality statistics using the underlying cause of death (UCOD) and deaths with any mention of IHD in death certificates (MCOD) from ICD-10 codes I20-I25 was performed between 2008 and 2022. A total of 134,327 death certificates reported IHD-related deaths, representing 18.6% of all deaths. Proportional mortality decreased from 14.6% in 2008 to 7.8% in 2022 for deaths with IHD as the UCOD and from 23.5% to 14.6% for deaths with IHD among the MCOD. A more pronounced decline of proportionate and case-specific mortality rate was seen in women. The decline in mortality over the whole study period was larger for acute (vs. chronic) IHD. The COVID-19 pandemic led to a marked increase in mortality in 2020 (+12.2%) with a subsequent further decline. IHD-related deaths displayed a typical seasonal pattern with more deaths during winter. The prevalence of cardiovascular risk factors was higher in IHD (vs. no IHD) deaths: this association appeared more pronounced in younger adults. We provided an analysis of epidemiological trends in IHD-related mortality and prevalence of risk factors. Our findings indicate a change in the pattern of cardiovascular deaths and may suggest a switch in death from acute to chronic conditions. • Epidemiological analysis of Veneto region (5.000.000 population, 2008–2022) • The mortality rate due to ischemic heart disease has progressively decreased • The decline in cardiovascular mortality was more pronounced among women • The mortality reduction was driven by acute (vs. chronic) cardiovascular syndromes • In 2020, there was a transient increase attributable to the COVID-19 pandemic [ABSTRACT FROM AUTHOR]

The New York City (NYC) initiated a new default speed limit law on November 7th, 2014, where speed limits on all road segments without a posted speed limit were reduced from 30 mph to 25 mph. The safety effectiveness of citywide speed limit reduction in an urban setting like NYC has been understudied in the literature. The high-density road network of NYC could lead to a significant spatial spillover effect of speed limit reduction on its neighboring sites. In addition, citywide speed limit reduction exerts much more treatment sites than control sites, which makes it challenging to identify sufficient control sites with similar covariates as the treated ones and thus may lead to confounding bias. Furthermore, there could also exist a time trend in crash observations caused by unobserved factors (e.g., enforcement, driving behaviors). To jointly account for spatial spillover effect, confounding bias, and time trend, this study proposes a novel causal inference approach integrating propensity score matching (PSM) and spatial difference-in-differences (SDID) to estimate the safety effectiveness of citywide speed limit reduction in NYC. The PSM utilizes a logistic generalized additive model (GAM) to capture the nonlinear relationship between covariates and the treatment indicator to reduce bias due to confounding variables. Moreover, the matched data are used to develop the SDID model that simultaneously captures spatial spillover effect and time trend via the extended difference-in-differences (DID) structure. The proposed causal approach suggests that the speed limit reduction would result in a 62.09% decrease in fatal crashes, with the spatial spillover effect found to be statistically significant. However, it does not indicate a significant change in injury and property-damage-only crashes as a result of the speed limit reduction. This study adds to the literature a robust causal inference approach for safety evaluation and provides researchers, practitioners, policy-makers insights into the safety effectiveness of the speed limit reduction in an urban setting. [ABSTRACT FROM AUTHOR]

Background: Synchronous colorectal cancer (CRC) has been associated with higher postoperative morbidity and mortality rates compared to solitary CRC. The influence of improved CRC care and introduction of screening on these outcomes remains unknown. This study aimed to evaluate time trends in incidence, population characteristics, and short-term outcomes of synchronous CRC patients at the population level over a 10-year time period. Methods: Data of all patients that underwent resection for primary CRC were extracted from the Dutch ColoRectal Audit (2010–2019). Analyses were stratified for solitary and synchronous colon and rectal cancer. Multilevel logistic regression analyses were used to determine factors associated with pathological and surgical outcomes. Results: Among 100,474 patients, 3.1% underwent surgery for synchronous CRC. A screening-related decrease for surgically treated left-sided solitary and synchronous colon cancer and a temporary increase for exclusively right-sided colon cancer were observed. Synchronous CRC patients had higher rates of complicated postoperative course, failure to rescue, and mortality. Bilateral synchronous colon cancer was more often treated with subtotal colectomy (25.4%) and demonstrated higher rates of surgical complications, reinterventions, prolonged hospital stay, and mortality than other synchronous tumor locations. Discussion: National bowel screening resulted in contradictory effects on surgical resections for synchronous CRCs depending on sidedness. Bilateral synchronous colon cancer required more often extended resection resulting in significantly worse outcomes than other synchronous tumor locations. Identification of low volume, high complex CRC subpopulations is relevant for individualized care and has implications for case-mix correction and benchmarking in clinical auditing. [ABSTRACT FROM AUTHOR]

The goal of the current study is to assess whether the scores of Brief Rating of Aggression by Children and Adolescents (BRACHA) at the emergency room (ER) can predict the aggressive incidents at pediatric psychiatric inpatient units. The study aims to identify predictors for two outcome measurements: 1) hazard rates for the first aggressive incident and 2) numbers of days between admission and the first aggressive incident, using the Cox regression model and Poisson regression model, respectively. The clinical records of a total of 5,610 adolescents admitted into the pediatric psychiatric inpatient units of Cincinnati Children's Hospital Medical Center were extracted for the analysis. The aggressive incident was defined as a score >0 from any category of the Overt Aggression Scale (OAS) and the high-aggressive incident was defined as a score ≥ 2 from any category of the OAS. The results indicate that the BRACHA score was not associated with high-aggressive incidents (hazard ratio: 0.98, p = 0.7543). Similarly, the BRACHA scores was only associated with the number of days from admission to the first aggressive incident (Poisson regression coefficient: 0.24, p < 0.0001) but not the number of days from admission to the first high-aggressive incident (Poisson regression coefficient: 0.03, p = 0.3994). Furthermore, the second peak of first aggressive incidents during the hospitalization highlights the importance of interventions at the end of the inpatient treatment course. To summarize, BRACHA scores based on initial assessments at the ER could correlate with first aggressive incidents, but not the first high-aggressive incidents. [ABSTRACT FROM AUTHOR]

• In this single center study, rates of ICU delirium and coma decreased over time. • Despite recent sedation guidelines, orders for benzodiazepines did not change over time, while orders for opioids did increase. • Higher level of consciousness and later time in years were associated with lower odds of delirium but did not entirely explain the change in yearly rates. Effects of clinical practice changes on ICU delirium are not well understood. Determine ICU delirium rates over time. Data from a previously described screening cohort of the Pharmacological Management of Delirium trial was analyzed. Richmond Agitation-Sedation Scale (RASS) and Confusion Assessment Method for the ICU (CAM-ICU) were assessed twice daily. We defined: A ny delirium (positive CAM-ICU at any time during ICU stay) and ICU-acquired delirium (1st CAM-ICU negative with a subsequent positive CAM-ICU). Mixed-effects logistic regression models were used to test for differences. 2742 patient admissions were included. Delirium occurred in 16.5%, any delirium decreased [22.7% to 10.2% (p < 0.01)], and ICU-acquired delirium decreased [8.4% to 4.4% (p = 0.01)]. Coma decreased from 24% to 17.4% (p = 0.04). Later ICU years and higher mean RASS scores were associated with lower odds of delirium. Delirium rates were not explained by the measured variables and further prospective research is needed. [ABSTRACT FROM AUTHOR]

Background: Many of the health benefits of tea have been attributed to its flavonoid content. Tea consumption in US adults varies by socioeconomic status (SES).Objectives: The present objective was to explore intakes of total flavonoids and flavonoid subclasses by participant sociodemographics and by patterns of tea consumption.Methods: The present analyses were based on 2 d of dietary recalls for 17,506 persons aged >9 y in the 2011-2016 NHANES. The What We Eat in America nutrient composition database was merged with the USDA Expanded Flavonoid database, which included total flavonoids and flavan-3-ols (including catechins), flavanones, flavonols, anthocyanidins, flavones, and isoflavones. Flavonoid intakes were compared by sex, age, race/ethnicity, education, and income-to-poverty ratio (IPR) in univariate analyses. Flavonoid intakes of children and adults were also compared by tea consumption status. Time trends in flavonoid intakes were also examined.Results: Mean total flavonoid intake was 219 mg/d, of which flavan-3-ols provided 174 mg/d, or 79%. The highest total flavonoid intakes were found in adults aged 51-70 y (293 mg/d), non-Hispanic whites (251 mg/d) and in groups with college education (251 mg/d) and higher income (IPR >3.5: 249 mg/d) (P < 0.001 for all). The socioeconomic gradient was significant for anthocyanidins, flavonols, and flavones (P < 0.001 for all) but not for flavan-3-ols, and persisted across 3 cycles of NHANES. Adult tea consumers had higher intakes of total flavonoids (610 mg/d compared with 141 mg/d) and flavan-3-ols (542 mg/d compared with 97.8 mg/d) than did nonconsumers (P < 0.001). Time trend analyses showed that both tea consumption and flavonoid intakes were unchanged from 2011 to 2016.Conclusions: Flavonoid intakes in children and adults in the NHANES 2011-16 sample were associated with higher SES and were largely determined by tea consumption. Studies of diet and disease risk need to take sociodemographic gradients and eating and drinking habits into account. [ABSTRACT FROM AUTHOR]

To prevent diseases arising from exposure to toxic metals, more knowledge about their temporal changes is needed, especially in children, the most vulnerable group. This study follows temporal changes in blood lead (BPb), mercury (BHg) and cadmium (BCd) levels in schoolchildren (8–11 years old) from two cities in southern Sweden. One blood sample per 773 children was used for time trend analyses between 2007 and 2022. One further blood sample re-sampled after 2 years, were used to assess intra-individual time trends of BPb (n = 377), BCd (n = 102) and BHg (n = 53) between 1979 and 2019. Geometric mean (range) of BPb, BCd and BHg concentrations during 2007–2022 was 9.9 (2.3–59), 0.09 (0.03–0.34) and 0.73 (0.02–8.2) μg/L, respectively. Living close to a Pb smelter resulted in higher levels of all three metals compared with living in the city or rural area. Annually, the concentrations clearly decreased for BPb (−4.9%, p < 0.001) and weakly for BCd (−0.6%, p = 0.013), while BHg slightly increased (+1.4%, p = 0.029). When stratified by residential area, the decrease of BCd and increase of BHg were significant only in the urban area (−1.8% and +2.8%, respectively; p < 0.01). The BPb decrease rate was the highest in the urban area followed by the rural and Pb smelter areas (−5.8% > -4.5% > -3.9%; p < 0.001). For children re-analysed during 1979–2019, a significant decrease was observed only for BPb (−6.8%; p < 0.001), with a 2% higher decrease rate in the period before than after the Pb-gasoline ban in 1994. The preventive measures against Pb pollution are reflected in the constant decrease of BPb levels over time. However, the area close to a Pb smelter, as indicated by a slower Pb decrease rate, might need further and stricter preventive measures. Exposure to Hg and Cd was low, however, the slight increase in BHg and only a minor decrease in BCd, indicate the need for continuous biomonitoring of children. [Display omitted] • In 2007–2022 we studied BPb, BCd and BHg levels in 773 schoolchildren in Sweden • The highest metal concentrations were found in children living near a Pb smelter. • BPb decreased with −4.9%/year, BCd negligibly decreased, and BHg slightly increased • Intra-individual data in 1979–2019 showed significant decreasing trend only for BPb • Continuous biomonitoring of children is needed [ABSTRACT FROM AUTHOR]

[Display omitted] The UV filters octocrylene (OC) and 2-ethylhexyl salicylate (EHS) are commonly used in sunscreens and frequently detected in environmental media. However, knowledge on human exposures is scarce. In this human biomonitoring (HBM) study, we analyzed concentrations of exposure biomarkers specific to OC (CPAA, DOCCA, 5OH-OC) and EHS (5OH-EHS, 5oxo-EHS, 5cx-EPS) in 24-h urine samples (n = 420) from the German Environmental Specimen Bank (ESB). These samples were collected from German students (20–29 years; 30 males/30 females per year) between 1996 and 2020 (4-year intervals; collection in winter). We found continuously increasing OC and EHS exposures (Jonckheere-Terpstra; p < 0.001) documented by very few to no samples with concentrations of the most sensitive biomarkers CPAA and 5cx-EPS above the limit of quantification (LOQ) in 1996 (5 % and 0 %, respectively) and reaching 100 % and 93 % above the LOQ in 2016, with median concentrations of 4.79 and 0.071 µg/L, respectively. In 2020, biomarker concentrations slightly decreased to 3.12 µg/L CPAA (97 %>LOQ) and 0.060 µg/L 5cx-EPS (88 %>LOQ). This general trend was confirmed by the other biomarkers, however at lower detection rates. Based on metabolite excretion in the 24-h urine samples and human toxicokinetic data, we calculated maximum daily intakes (DI) of 17 µg/(kg bw * d) OC and 59 µg/(kg bw * d) EHS. Based on a derived no-effect level (DNEL) of 0.8 mg/(kg bw * d), the OC exposures of individuals in our study did not indicate any health risk. Similarly, for EHS all biomarker concentrations were well below the HBM-I values of 12 µg/L 5OH-EHS and 11 µg/L 5cx-EPS. Our data proves the general applicability of specific OC and EHS metabolites for HBM in the general population and shows clearly increasing exposures. Higher (co-)exposures must be expected in populations with increased sunscreen use such as (summer) vacationers, children and outdoor workers. [ABSTRACT FROM AUTHOR]

• Car traffic slowed down in France from the 2000′s, in relation to income growth. • We implement a sequential model of car mileage to simulate car traffic up to 2050. • Additional factors might cause a decreasing trend in car mileage after 2007. • Assuming the perpetuation of this time trend, car traffic would peak by 2040. • This peak could even come closer if extending previous trends about income growth. After decades of uninterrupted growth, car traffic temporarily levelled off during the 2000′s in France, before coming back to growth after 2008. However, there are reasons to believe that car traffic growth is potentially limited, among which completion of the diffusion process for car ownership, limited travel time budgets, decreasing returns of additional car travel. In this study, we implement a disaggregate model at the household level to project future car ownership and car mileage per household in France, along with total car traffic, accounting for demographic growth. Our model relies on a sequential approach using panel data, with an ordered response probit model for the number of vehicles, including saturation thresholds by vehicle rank, and a log-linear model for car mileage, conditional on the number of vehicles, both with correlated random effects. A time trend is also incorporated to account for the decreasing household car mileage that was noticed over the last twenty years, which is not entirely explained by decreasing household size and the gradual decline of income growth. Assuming this trend to go on, total car traffic in France would grow only a little by 2050, despite demographic growth, and start decreasing from 2040. We discuss these results by questioning the structural nature of this trend. [ABSTRACT FROM AUTHOR]

DINCH (cyclohexane-1,2-dicarboxylic acid-diisononyl ester) is a phthalate plasticizer substitute introduced into the market in 2002. It is increasingly used especially in the production of toys, food contact materials and medical devices. In this measurement campaign on 24-h urine samples of young adults (20–29 years) from the German Environmental Specimen Bank (ESB) collected in 2010, 2011, 2013, 2015 and 2017 (in total 300 samples, 60 samples/year) we analyzed three specific, oxidized DINCH metabolites (OH-MINCH: cyclohexane-1,2-dicarboxylic acid-mono(hydroxy-isononyl) ester; cx-MINCH: cyclohexane-1,2-dicarboxylic acid-mono(carboxy-isooctyl) ester, oxo-MINCH: cyclohexane-1,2-dicarboxylic acid-mono(oxo-isononyl) ester). We merged these data with earlier data of the ESB from the years 1999–2012 and are now able to report levels and time trends of internal DINCH exposure from 1999 to 2017. After first detections of the major oxidized DINCH metabolite OH-MINCH in 2006 (6.7%) detection rates rapidly increased to 43.3% in 2009, 80% in 2010 and 98.3% in 2011 and 2012. From the year 2013 on we could detect OH-MINCH in every urine sample analyzed. The median concentrations of OH-MINCH rapidly increased from 0.15 μg/L in 2010 to twice the concentration in 2011 (0.31 μg/L) with further increases in 2013 (0.37 μg/L), 2015 (0.59 μg/L) and 2017 (0.70 μg/L). Similar increases, albeit at lower detection rates and concentration levels, could be observed for cx-MINCH and oxo-MINCH. All metabolites strongly correlate with each other. For the ESB study population, DINCH exposures are still far below health based guidance values such as the German Human Biomonitoring Value (HBM-I; 4,500 μg/L for the sum of OH-MINCH and cx-MINCH) or the tolerable daily intake (TDI) of EFSA (1 mg/kg bw/d). The median daily DINCH intake (DI) calculated for 2017 was 0.23 μg/kg bw/d, thus 4,310-times lower than the TDI. The maximum DI calculated for one individual in 2012 (42.60 μg/kg bw/d) was a factor of more than 20 below the TDI. The ongoing increase in DINCH exposure needs to be closely monitored in the future, including populations with potentially higher exposures such as children. This close monitoring will enable timely exposure and risk reduction measures if exposures reached critical levels, or if new toxicological data lead to lower health based guidance values. DINCH belongs to the European Human Biomonitoring Initiative (HBM4EU) priority substances for which policy relevant questions still have to be answered. [ABSTRACT FROM AUTHOR]

• Antimicrobial use in Dutch companion animal clinics is changing and decreasing. • Aminopenicillins account for the largest group of used antimicrobials. • Strong seasonal differences in antimicrobial use are observed. • The distribution of different animal species appears to affect antimicrobial use. • Especially the classes of antimicrobials prescribed could be further optimised. Any antimicrobial use (AMU) in humans and animals selects for antimicrobial resistance (AMR) and responsible AMU should therefore be promoted both in human and veterinary medicine. Insight into current AMU in companion animal clinics is necessary to be able to optimise antimicrobial (AM) prescribing behaviour. The objective of this study was to describe systemic AMU in 44 Dutch companion animal clinics over a 3-year time period (2012–2015), using retrospectively collected data. The number of Defined Daily Doses for Animals (DDDAs) per month and per clinic were calculated from prescription data for total, 1st, 2nd and 3rd choice AMU (classification according to Dutch policy on veterinary AMU). Time trends, seasonality and the influence of potential determinants (e.g., the number of dogs, cats and rabbits per clinic and other clinic characteristics) were explored using statistical modelling. Overall, the findings show that total AMU decreased over time and a shift in used classes of antimicrobials towards more 1st choice AMs was visible. Mean total AMU decreased from 1.82 DDDA/year in 2012–2013 to 1.56 DDDA/year in 2014-2015. Aminopenicillins, with and without clavulanic acid, accounted for the largest group of antimicrobials used; 38.7% (2012–2013), 40.2% (2013–2014) and 39.3% (2014–2015) of total AMU, respectively. Strong seasonal differences in AMU were found, with highest AMU in July-August and lowest in February-March. The distribution of different animal species per clinic appeared to affect AMU as well. In clinics with a larger proportion of dogs, 2nd choice AMU was significantly higher, whereas in clinics with a larger proportion of rabbits, 2nd choice AMU was significantly lower. Despite the decrease of AMU during the study period, there is still room for improvement left, especially with regard to the antimicrobial classes prescribed. According to Dutch classification of veterinary AMU, 1st choice AMs should be used as empirical therapy. A decrease in 2nd (might select for ESBL-producing bacteria) and 3rd choice AMU (i.e. fluoroquinolones and 3rd generation cephalosporins) should be aimed for. [ABSTRACT FROM AUTHOR]

The occurrence of classical and emerging halogenated flame retardants in bird samples collected between 2010–17 from the Castrejón reservoir (central Spain) was studied. Different wetland bird samples were analysed, including unhatched bird eggs and liver of dead nestlings. Polybrominated diphenylethers (PBDEs) were detected in all the samples at high concentration values, with levels up to 5167 ng/g lw. Dechloranes were found in 78% of analysed samples, but at lower concentration levels, between not detected (nd) and 2153 ng/g lw. The time trend evaluation over the sampling period showed an approximately 50% decline in mean concentrations of PBDEs. However, the most recent data for PBDEs (2016–17) still indicate that, in some cases, and based on reported LOECs, wetland birds were exposed to PBDE concentrations that are associated with possible ecological hazards. • PBDEs were detected at high concentrations, with levels up to 5167 ng/g lw. • Dechloranes were found in 78% of samples, at concentrations up to 2153 ng/g lw. • Time trend evaluation for PBDEs along 2010–2017 showed a level decline. • Based on reported LOECs, birds were still exposed to PBDEs associated to ecological hazards. [ABSTRACT FROM AUTHOR]

Abstract We investigated the temporal trend of mercury (Hg) in arctic foxes from Svalbard, Norway sampled in the period 1997–2014 (n = 109, from 11 trapping seasons). We used linear models to investigate the effect of trapping season, feeding habits (δ 13C), food availability from marine and terrestrial ecosystems (reindeer carcasses and sea ice cover), sex, age and body condition on liver total Hg (THg) levels. Liver THg levels increased in arctic foxes with 7.2% (95% CI: 2.3, 9.6) per year when the concentrations were adjusted for variation of δ 13C, sea ice cover, and reindeer carcasses, whereas the raw annual trend was 3.5% (CI: −0.11, 7.2). However, the THg levels in arctic foxes from Svalbard are still lower than other marine mammals. We also demonstrate that arctic fox terrestrial food consumption is important for lowering the overall THg levels in this species. Graphical abstract Unlabelled Image Highlights • We analyzed liver concentrations of THg in 109 arctic foxes from Svalbard. • THg levels in arctic foxes increased with 7.2% per year from 1997 to 2014. • The increase in THg per year is lower than in other Arctic regions. • Terrestrial food consumption reduced THg levels in arctic foxes. [ABSTRACT FROM AUTHOR]

Abstract Background While numerous studies have shown that the impact of cold waves is decreasing as result of various processes of adaptation, far fewer have analysed the time trend shown by such impact, and still fewer have done so for the different provinces of a single country, moreover using a specific cold waves definition for each. This study thus aimed to analyse the time trend of the impact of cold days on daily mortality in Spain across the period 1983–2003. Methods For study purposes, we used daily mortality data for all natural causes except accidents in ten Spanish provinces. The time series was divided into three subperiods. For each period and province, the value of T threshold was obtained via the percentile corresponding to the cold day's definition for that province obtained in previous studies. Relative Risks (RRs) and Population Attributable Fraction (PARs) were calculated using Generalised Linear Models (GLMs) with the Poisson regression link. Seasonalities, trends and autoregressive components were controlled. Global RRs and ARs were calculated with the aid of a meta-analysis with random effects for each of the periods. Results The results show that the RRs for Spain as a whole were 1.12 (95% CI: 1.08 1.16) for the first period, 1.15 (95% CI: 1.09 1.22) for the second and 1.18 (95% CI: 1.10 1.26) for the third. The impact of cold days has risen slightly over time, though the differences were not statistically significant. These findings show a clearly different behaviour pattern to that previously found for heat. Conclusion The results obtained in this study do not show a downward trend for colds days. The complexity of the biological mechanisms involved in cold-related mortality and the lack of robust results mean that more research must be done in this particular field of public health. Graphical abstract Unlabelled Image Highlights • This study analyses the time trend of the impact of cold on daily mortality in Spain. • The results obtained show a clearly different behaviour pattern to that found for heat. • The impact of cold days has remained constant over time. • It is necessary to implement prevention plans to reduce the impact of cold on health. [ABSTRACT FROM AUTHOR]

Highlights • A long-term (36-year) soil monitoring data was analyzed. • Soil chemical properties considered indicative of acidification trends in soils. • Statistical analysis indicated decreasing trends in pH and base saturation. • Necessary to distinguish the importance of statistical and biological differences. Abstract Long-term soil acidification monitoring was initiated in 1981 to track potential effects of acidic atmospheric deposition on soils in Alberta, Canada. Six of eight long-term sampling sites were located in forest ecosystems on sandy soils in northern and central Alberta, and two were situated in grasslands on sandy and fine-loamy soils in southern Alberta. Sampling was undertaken every four or five years, with 12 replicate samples taken from seven depth increments from 0–60 cm at each site. The statistical analysis of pH, exchangeable base saturation (BS) percentage, and solution base cation (BC) to aluminum (Al) ratio was conducted in the topmost soil layers (0–2, 2–5 and 5–10 cm). Analysis of variance (ANOVA) and linear regression indicated decreasing trends in pH and BS percentage in some of the sites. Comparison of the initial and most recent monitoring data indicated decreases of up to 0.5 pH units in these layers at five of the forested sites. At two forested sites located in the vicinity of oil sands and heavy oil processing plants, decreasing BS was observed early in the monitoring period, but the trend showed more variability since 2000, even though pH has continued to decline since 1981. BC to Al ratio showed statistically significant variations within some sites over time, but except for a downward trend at one central Alberta site, there were no overall patterns evident at the other sites over time. Both grassland sites had much higher BC to Al ratio and exchangeable BS percentages than the forested sites, and acidification trends were not detected at either of these sites. ANOVA and linear modelling approaches showed significant differences even in instances where pH differed by 0.1–0.2 units, or where other parameters showed very small differences. It is therefore necessary to distinguish between statistically important and biologically important differences in this monitoring program, which is intended to continue for several more years. [ABSTRACT FROM AUTHOR]

Abstract Objectives This study analyzed the relative time trends of prices of healthy versus unhealthy foods in South Korea for the 20 years from 1995 to 2015. Study design Time series analysis was used. Methods We analyzed price trends of selected food items in the food groups of grains, vegetables, meats, sweets, spices, fast foods, and non-alcoholic beverages. We obtained nominal prices from the monthly reports of the 2006 Consumer Price Survey for representative items in each food group. Results The real price of processed meat increased by 1.2 percentage points less than the overall Consumer Price Index (CPI) increase, whereas beef prices increased by 2.4 percentage points more than the CPI increase. The price of soda was cheaper than that of other non-alcoholic beverages, whereas the real prices of milk showed statistically significantly larger yearly increases (by 1.4 percentage points, respectively) than that of the CPI. The yearly increases in the real prices of pizza, hamburgers, and fried chicken—three representative fast-food items that were mostly consumed by eating out or through home delivery—were statistically significantly less than those of the CPI (by 1.5, 1.4, and 0.3 percentage points, respectively). Conclusions Our results show that relatively healthy foods showed higher real price increases than the CPI increase, whereas the opposite occurred for unhealthy foods. Highlights • We analyzed the relative time trends of prices of selected foods in South Korea. • Time series analysis was used for the 20 years from 1995 to 2015. • Relatively healthy foods showed higher real price increases than the Consumer Price Index increase. [ABSTRACT FROM AUTHOR]

Many of the studies that analyze the future impact of climate change on mortality assume that the temperature that constitutes a heat wave will not change over time. This is unlikely, however, given the process of adapting to heat changes, prevention plans, and improvements in social and health infrastructure. The objective of this study is to analyze whether, during the 1983–2013 period, there has been a temporal change in the maximum daily temperatures that constitute a heat wave (T threshold ) in Spain, and to investigate whether there has been variation in the attributable risk (AR) associated with mortality due to high temperatures in this period. This study uses daily mortality data for natural causes except accidents CIEX: A00-R99 in municipalities of over 10,000 inhabitants in 10 Spanish provinces and maximum temperature data from observatories located in province capitals. The time series is divided into three periods: 1983–1992, 1993–2003 and 2004–2013. For each period and each province, the value of T threshold was calculated using scatter-plot diagram of the daily mortality pre-whitened series. For each period and each province capitals, it has been calculated the number of heat waves and quantifying the impact on mortality through generalized linear model (GLM) methodology with the Poisson regression link. These models permits obtained the relative risks (RR) and attributable risks (AR). Via a meta-analysis, using the Global RR and AR were calculated the heat impact for the total of the 10 provinces. The results show that in the first two periods RR remained constant RR: 1.14 (CI95%: 1.09 1.19) and RR: 1.14 (CI95%: 1.10 1.18), while the third period shows a sharp decrease with respect to the prior two periods RR: 1.01 (CI95%: 1.00 1.01); the difference is statistically significant. In Spain there has been a sharp decrease in mortality attributable to heat over the past 10 years. The observed variation in RR puts into question the results of numerous studies that analyze the future impact of heat on mortality in different temporal scenarios and show it to be constant over time. [ABSTRACT FROM AUTHOR]

Aims: Our aim was to assess causes of death and temporal changes in excess mortality among patients with new-onset type 2 diabetes in Skaraborg, Sweden.Methods: Patients from the Skaraborg Diabetes Register with prospectively registered new-onset type 2 diabetes 1991-2004 were included. Five individual controls matched for sex, age, geographical area and calendar year of study entry were selected using population records. Causes of deaths until 31 December 2014 were retrieved from the Cause of Death Register. Adjusted excess mortality among patients and temporal changes of excess mortality were calculated using Poisson models. Cumulative incidences of cause-specific mortality were calculated by competing risk regression.Results: During 24 years of follow-up 4364 deaths occurred among 7461 patients in 90,529 person-years (48.2/1000 person-years, 95% CI 46.8-49.7), and 18,541 deaths in 479,428 person-years among 37,271 controls (38.7/1000 person-years, 38.1-39.2). The overall adjusted mortality hazard ratio was 1.47 (p < .0001) among patients diagnosed at study start 1991 and decreased by 2% (p < .0001) per increase in calendar year of diagnosis until 2004. Excess mortality was mainly attributed to endocrine and cardiovascular cause of death with crude subdistributional hazard ratios of 5.06 (p < .001) and 1.22 (p < .001).Conclusions: Excess mortality for patients with new-onset type 2 diabetes was mainly attributed to deaths related to diabetes and the cardiovascular system, and decreased with increasing year of diagnosis 1991-2004. Possible explanations could be temporal trends of earlier diagnosis due to lowered diagnostic thresholds and intensified diagnostic activities, as well as improved treatment. [ABSTRACT FROM AUTHOR]

Aims: To identify how efforts to control the diabetes epidemic and the resulting changes in diabetes mellitus, type II (T2D) incidence and survival have affected the time-trend of T2D prevalence.Methods: A newly developed method of trend decomposition was applied to a 5% sample of Medicare administrative claims filed between 1991 and 2012.Results: Age-adjusted prevalence of T2D for adults age 65+ increased at an average annual percentage change of 2.31% between 1992 and 2012. Primary contributors to this trend were (in order of magnitude): improved survival at all ages, increased prevalence of T2D prior to age of Medicare eligibility, decreased incidence of T2D after age of Medicare eligibility.Conclusions: Health services supported by the Medicare system, coupled with improvements in medical technology and T2D awareness efforts provide effective care for individuals age 65 and older. However, policy maker attention should be shifted to the prevention of T2D in younger age groups to control the increase in prevalence observed prior to Medicare eligibility. [ABSTRACT FROM AUTHOR]

In most countries, incidence and mortality for Parkinson's disease (PD) have not been monitored by surveillance registries, although it could demonstrate the need for primary and tertiary prevention. To examine 25-year trends in first-time hospitalizations for PD in Denmark and subsequent short and long-term mortality. In a nationwide population-based cohort we identified all 34,947 individuals with a first-time hospitalization for PD from 1995 through 2019. We calculated standardized incidence rates of PD and 1-year and 5-year mortality by sex. Mortality rates were compared with a reference cohort randomly selected from the background population matched on sex, age, and index date. The annual standardized incidence rate of PD was relatively stable during the study period in both men and women. The incidence of PD was higher in men than in women and with the highest incidence in those aged 70–79 years. One and 5-year mortality risk after first-time hospitalization for PD was similar for men and women, and decreased by around 30% and 20%, respectively, between 1995 and 2019. The matched reference cohort had a similar decline in mortality over time. The rate of first-time hospitalization for PD was relatively stable between 1995 and 2019, whereas subsequent short and long-term mortality declined during the period as in the reference cohort. • The incidence of Parkinson's disease was relative stable in Denmark between 1995 and 2019. • The incidence of Parkinson's disease was highest in men and at age 70–79 years. • During the time period one and five year mortality risk decreased in patient with Parkinson's disease. [ABSTRACT FROM AUTHOR]

Summary Objectives This study aimed to investigate the disparities in pneumonia-specific under-five mortality rates (U5MRs) among and within three geographic regions in Mainland China from 1996 to 2015. Methods Data were obtained from the national Under-Five Child Mortality Surveillance System and grouped into 2-year periods. The Cochran–Armitage trend test and Cochran–Mantel–Haenszel test were used to assess trends and differences in the pneumonia-specific U5MRs among and within geographic regions. Relative risks (RRs) and 95% confidence intervals (95% CIs) were calculated. Results The pneumonia-specific U5MR decreased by 90.6%, 89.0%, and 83.5% in East, Middle, and West China, respectively, with a larger decrease in rural areas. The pneumonia-specific U5MR was highest in West China, and was 7.2 (95% CI 5.9–8.7) times higher than that in East China in 2014–2015. In 2014–2015, the RRs were 1.7 (95% CI 1.2–2.5), 1.6 (95% CI 1.1–2.1), and 3.4 (95% CI 2.8–4.0) between rural and urban areas in East, Middle, and West China, respectively. Conclusions Pneumonia-specific U5MRs decreased from 1996 to 2015 across China, particularly in rural areas. However, disparities remained among and within geographic regions. Additional strategies and interventions should be introduced in West China, especially the rural areas, to further reduce the pneumonia-specific U5MR. [ABSTRACT FROM AUTHOR]

Objective/Background To review the incidence of post-carotid endarterectomy (CEA) cranial nerve injury (CNI), and to evaluate the risk factors associated with increased CNI risk. Methods The study was a meta-analysis. Pooled rates with 95% confidence intervals (CIs) were calculated for CNIs after primary CEA. Odds ratios (ORs) were calculated for potential risk factors. A fixed-effects model or a random effects model (Mantel–Haenszel method) was used for non-heterogeneous and heterogeneous data, respectively. Meta-regression analysis was performed to examine the influence of publication year upon CNI rate. Results Twenty-six articles, published between 1970 and 2015, were included in the meta-analysis, corresponding to 20,860 CEAs. Meta-analysis revealed that the vagus nerve was the most frequently injured cranial nerve (pooled injury rate 3.99%, 95% CI 2.56–5.70), followed by the hypoglossal nerve (3.79%, 95% CI 2.73–4.99). Fewer than one seventh of these injuries are permanent (vagus nerve: 0.57% [95% CI 0.19–1.10]; hypoglossal nerve: 0.15% [95% CI 0.01–0.39]). A statistically significant influence of publication year on the vagus and hypoglossal nerve injury rate was found, with the injury rate having decreased from about 8% to 2% and 1%, respectively, over the last 35 years. Urgent procedures (OR 1.59, 95% CI 1.21–2.10; p = .001), as well as return to the operating room for a neurological event or bleeding (OR 2.21, 95% CI 1.35–3.61; p = .002) were associated with an increased risk of CNI, whereas no statistically significant association was found between CNIs and the type of anaesthesia, the use of a patch, redo operation, and the use of a shunt. Conclusion The vagus nerve appears to be the most frequently injured cranial nerve after CEA, followed by the hypoglossal nerve, with only a small proportion of these injuries being permanent. The CNI rate has significantly decreased over the past 35 years to a point indicating that CNIs should not be considered a major influencing factor in the decision making process between CEA and stenting. [ABSTRACT FROM AUTHOR]

The broadband herbicide glyphosate (N-[phosphonomethyl]-glycine) and its main metabolite aminomethylphosphonic acid (AMPA) were analyzed by GC-MS-MS in 24h-urine samples cryo-archived by the German Environmental Specimen Bank (ESB). Samples collected in 2001, 2003, 2005, 2007, 2009, 2011, 2012, 2013, 2014, and 2015 were chosen for this retrospective analysis. All urine samples had been provided by 20 to 29 years old individuals living in Greifswald, a city in north-eastern Germany. Out of the 399 analyzed urine samples, 127 (=31.8%) contained glyphosate concentrations at or above the limit of quantification (LOQ) of 0.1μg/L. For AMPA this was the case for 160 (=40.1%) samples. The fraction of glyphosate levels at or above LOQ peaked in 2012 (57.5%) and 2013 (56.4%) after having discontinuously increased from 10.0% in 2001. Quantification rates were lower again in 2014 and 2015 with 32.5% and 40.0%, respectively. The overall trend for quantifiable AMPA levels was similar. Glyphosate and AMPA concentrations in urine were statistically significantly correlated (spearman rank correlation coefficient=0.506, p≤0.001). Urinary glyphosate and AMPA levels tended to be higher in males. The possible reduction in exposure since 2013 indicated by ESB data may be due to changes in glyphosate application in agricultural practice. The ESB will continue monitoring internal exposures to glyphosate and AMPA for following up the time trend, elucidating inter-individual differences, and contributing to the ongoing debate on the further regulation of glyphosate-based pesticides. [ABSTRACT FROM AUTHOR]

Trace elements are chemical contaminants spread in the environment by anthropogenic activities and threaten wildlife and human health. Many studies have investigated this contamination in apex raptors as sentinel birds. However, there is limited data for long-term biomonitoring of multiple trace elements in raptors. In the present study, we measured the concentrations of 14 essential and non-essential trace elements in the livers of the common buzzard (But eo buteo) collected in the United Kingdom from 2001 to 2019 and investigated whether concentrations have changed during this period. In addition, we estimated the importance of selected variables for modelling element accumulations in tissues. Except for cadmium, hepatic concentrations of harmful elements in most buzzards were lower than the biological significance level of each element. Hepatic concentrations of certain elements, including lead, cadmium, and arsenic, varied markedly seasonally within years. Their peak was in late winter and trough in late summer, except copper which showed an opposite seasonal pattern. In addition, lead in the liver consistently increased over time, whereas strontium showed a decreasing trend. Hepatic concentrations of cadmium, mercury, and chromium increased with age, whereas selenium and chromium were influenced by sex. Hepatic concentrations of arsenic and chromium also differed between different regions. Overall, our samples showed a low risk of harmful effects of most elements compared to the thresholds reported in the literature. Seasonal fluctuation was an important descriptor of exposure, which might be related to the diet of the buzzard, the ecology of their prey, and human activities such as the use of lead shot for hunting. However, elucidating reasons for these observed trends needs further examination, and biomonitoring studies exploring the effects of variables such as age, sex, and seasonality are required. [Display omitted] • Liver Pb, Cd, As, Se, Cu, and Co fluctuated seasonally within a year. • Fluctuation peak was in late winter and trough in late summer, except for Cu. • Liver Pb increased over the monitoring period. • Body and liver weights were negatively correlated with liver essential elements. • Relative importance of variables for predictive models of metal burden was estimated. [ABSTRACT FROM AUTHOR]

Over the last twenty-five years it has become evident that exposure to several phthalates can have adverse effects on human health, such as endocrine disruption. This led to a series of EU regulations that resulted in a decrease in the production volumes of the restricted phthalates and an increased production of substitutes. The current study describes the impact of regulations and changes in production and use of phthalates and their substitutes on internal exposure patterns in two European populations since the beginning of the 2000′ies. Using harmonised data from young adults in Denmark (Danish Young Men Study, n = 1,063, spot urine) and Germany (Environmental Specimen Bank, n = 878, 24-h urine) with repeated cross-sectional design (3–11 cycles per biomarker) we applied Locally Estimated Scatterplot Smoothing (LOESS) and Generalized Linear Models (GLMs) to estimate time trends and the role of covariates on the trend (e.g. age, BMI). Time trends of daily excretion (μg/24h) are comparable between the two samples for the regulated (DEHP, BBzP, DiNP, DnBP, DiBP, DiDP/DPHP) as well as the non-regulated substances (DMP, DEP, DINCH, DEHTP) although the rate of change differ for some of the compounds. GLM results indicate that the daily excretion of the most regulated phthalates has decreased over time (DEHP yearly about 12–16%, BBzP 5%, DnBP 0.3–17%, and DiBP 4–12%). Interestingly, also the non-regulated phthalates DMP and DEP decreased by 6–18% per year. In sharp contrast, the phthalate substitutes DINCH and DEHTP show very steep annual increases (∼10–68% and ∼100%, respectively) between 2009 and 2017. We did not find an effect of age, sex, BMI, or education on the time trend. The present study provides comparable insights into how exposure to phthalates and two of their substitutes have changed over the last two decades in Germany and Denmark. • Comparable time trends in Danish and German young adults. • Strongest decline per year for the regulated phthalates DEHP (16% in DYMS) and MnBP (17% in ESB). • Decline also for non-regulated phthalates DEP and DMP. • Harmonising 24-h urine and spot urine via estimating their 24-h excretion. • Substitutes DEHTP and DINCH show sharp yearly increases between 2009 and 2017. [ABSTRACT FROM AUTHOR]

Objectives: Road traffic injuries, particularly pedestrian injuries, are a major health issue among children worldwide. The present study quantitatively analyzed the time trends of child pedestrian injuries in Japan from 1975 to 2013 by age. Study design: Time trend analysis of nationally aggregated data. Methods: We analyzed police data on pedestrian injuries requiring medical treatment among children aged 0e15 years occurring between 1975 and 2013. To quantify the time trends of pedestrian injury morbidity rates and to identify change-points in the trends, joinpoint regression analysis was applied by age group. Children were categorized into the age groups of 0e3, 4e6, 7e9, 10e12, and 13e15 years old. Results: Preschool children aged 0e6 years old showed continuous declining trends throughout the study period; these declining trends accelerated in the 2000s. School-age children aged 7e15 years old showed minimal changes from the early 1970s to the 1990s; of this age group, children aged 7e12 years old showed slight but significant declining trends in the first half and increasing trends in the latter half of this period. Children aged 7e15 years old showed declining trends in the 2000s. Despite the consistent declining trends among all age groups in the 2000s, the younger age groups showed steeper declines during this period. Conclusions: The declining trends in all age groups in the 2000s may reflect the improved traffic environments in Japan although the environmental approaches are not yet sufficiently adopted yielding modest effects. The continuing contrast between preschool and school-age children may reflect different behaviour changes by age such as more restricted outdoor activities among young children. [ABSTRACT FROM AUTHOR]

[Display omitted] • First HBM of EQ in a larger cohort (N = 250) of young adults (20 – 29 years). • EQ metabolite EQI found in quantifiable concentrations in 91 % of the study samples. • Men showed higher exposure compared to women in this study. • Exposure reduction between 2016 and 2021 coincides with the EU ban of EQ. • Population representative HBM studies needed to support risk assessment of EQ. Human Biomonitoring (HBM) of emerging chemicals gained increasing attention within the EU in recent years. After evaluating the metabolism, we established a new HBM method for ethoxyquin (EQ), a feed additive, which was banned in 2017 due to concerns regarding the possible exposure of the general population to it and its highly toxic precursor p-phenetidine. The method was applied to 250 urine samples from the Environmental Specimen Bank collected between 2000 and 2021. The major metabolite EQI was quantified in the majority of the study samples illustrating the ubiquitous exposure of the non-occupationally exposed population. A rather constant exposure was observed until 2016 with a significant decline from 2016 to 2021. This drop falls within the EU wide ban of the chemical as a feed additive from June 2017 which led to a gradual removal until its complete suspension in June 2020. The daily intake (DI) was evaluated with respect to the reported derived no-effect level (DNEL) to estimate the potential health risks from EQ exposure. The median DI of 0.0181 µg/kg bw/d corresponds to only 0.01 % of the DNEL. Even the observed maxima up to 13.1 µg/kg bw/d only accounted for 10 % of the DNEL. Nevertheless, the values suggest a general exposure with the risk of higher burden in a low fraction of the population. In regard to the EQ associated intake of the carcinogen and suspected mutagen p-phenetidine, this level of exposure cannot be evaluated as safe. The recent decrease and the broad exposure substantiate the need for future HBM campaigns in population representative studies to further investigate the observed reductions, potentially find highly exposed subgroups and clarify the impact of the ban as feed additive on EQ exposure. [ABSTRACT FROM AUTHOR]

• The incidence of HPV-related oral and pharyngeal cancer seems stable between 1968 and 2017 which is not the case in much of the world. • The incidence of HPV-unrelated oral and pharyngeal cancers declined between 1968 and 2017 which is the case in much of the Western world. • Young cohorts had the lowest incidence of HPV-related cancers. HPV-related cancers increased from 1988 to 1997. To examine trends and age-period-cohort effects (APC) on oral and pharyngeal cancers incidence in Singapore between 1968 and 2017 by human papillomavirus (HPV) status. All diagnosed oral and pharyngeal cancers and population size were extracted from the Singapore Cancer Registry and the Department of Statistics Singapore, respectively. Anatomical subsites were used as a proxy for HPV infection. Prais-Winsten regression assessed trends of age-standardised incidence rate (ASIR) (per 100,000 person-years); Poisson regression assessed APC effects on HPV-related and HPV-unrelated cancers. Over 50 years, 1,618 HPV-related and 2,977 HPV-unrelated oral and pharyngeal cancers were diagnosed, with the highest ASIR in Indians (6.93), followed by Chinese (2.81), and Malays (1.81). Overall, ASIR HPV-related cancers were stable while HPV-unrelated cancers decreased. The male–female ASIR ratio reduced from 5.82 (1968–1977) to 4.0 (2008–2017) for HPV-related cancers, and from 2.58 (1968–1977) to 1.52 (2008–2017) for HPV-unrelated cancers. HPV-unrelated ASIR in males decreased, but in females only among Indians. HPV-related ASIR decreased only among Indian females. The cohort born between 1983 and 1992 had the lowest incidence of HPV-related cancers in males but the highest in HPV-unrelated cancers. Period effect mainly contributed to HPV-related cancer among males with increased incidence after 1997. Overall, the age effect was more pronounced in males. HPV-related cancers accounted for 1/3 of oral and pharyngeal cancers. A significant decline was observed only for HPV-unrelated cancers. The cohort effect was mainly attributed to HPV-unrelated cancer incidence, while the period effect largely contributed to HPV-related cancer incidence, but only among males. [ABSTRACT FROM AUTHOR]

A number of biomonitoring investigations were carried out in Italy between 2000 and 2018 by the Unit of Human Exposure to Environmental Chemicals of the Italian National Institute of Health (Rome). The investigations were characterized by different features (case-control or cross-sectional studies, participants from impacted or no impacted areas, etc), but despite the differences, it was possible to study the time trends of Σ 7 (PCDDs), Σ 10 (PCDFs), Σ 12 (DL-PCBs), and Σ 6 (NDL-PCBs) (analytical and TEQ cumulative concentrations, as appropriate). All the chemicals considered showed clear rates of a time-dependent concentration decrease, data having previously been adjusted for the sampled Region and subject age. Σ 7 (PCDDs) exhibited the fastest decrease with an average rate of −4.44 pg/g-fat year−1 (2009–2018), whereas Σ 6 (NDL-PCBs) was characterized by the slowest decrease with a rate of −0.771 ng/g-fat year−1 (2000–2018). A clear distinction between the decreasing rates of Σ 7 (PCDDs) and Σ 10 (PCDFs) was observed, as the latter decreased at half the rate of the Σ7(PCDDs). The slower rate of the Σ 10 (PCDFs) decline may be due to an ongoing source of PCDFs in the environment beyond those traditionally considered for this group of contaminants such as the production of PCDFs due to PCBs thermal conversion from matrices contaminated with PCBs. Production of PCDFs due to thermal conversion of matrices contaminated with PCBs could be an ongoing source which may be of concern because recent data have highlighted the diffusion of PCBs in the European environment. The decreasing rates of PCDDs + PCDFs, DL-PCBs, and PCDDs + PCDFs + DL-PCBs — original analytical data converted to "dioxin equivalents" — were respectively estimated as (pgTEQ/g-fat year−1) −2.08, −2.06, and −2.10, values exhibiting good compatibility between one another. [Display omitted] • In many countries the decrease of legacy POPs concentrations has been reported. • In Italy this decrease proceeds at comparable rates for "dioxin equivalents" data. • The decrease proceeds at different rates for different chemical classes/families. • There is a large difference between the decline in concentrations of the PCDDs and PCDFs. • The PCB decreases is the slowest one. [ABSTRACT FROM AUTHOR]

In this work, agricultural and background soil concentrations of p,p′- DDT, p,p′- DDE, HCB, α-, β- and γ-HCH from 1993 to 2012 were collected from 73 peer-reviewed publications, and analysed statistically. For the period 2003–2012 and for all chemicals, the mean concentration in agricultural soil is significantly higher than the concentration in background soil. In addition to the statistical analysis, concentrations of p,p′- DDT and α-HCH in soils were calculated with a global environmental fate and transport model. A decrease in the mean soil concentration from the first decade to the second was observed with the model, but this decrease is not visible in the measured concentrations, which could result from ongoing use of p,p′- DDT and α-HCH Furthermore, modelled background soil concentrations are generally lower than measurements. This implies that background soil may have received p,p′- DDT and α-HCH through additional routes not described by the model such as spray drift. [ABSTRACT FROM AUTHOR]

Background/purpose: Identifying trends in the prevalence and incidence of Parkinson's disease (PD) may yield information that supports public health goals. Our aim was to evaluate time-trend changes in the prevalence and incidence of PD in Taiwan between 2004 and 2011.Methods: This retrospective, nationwide, longitudinal study used the Taiwan National Health Insurance Research Database to identify patients with PD from 2004 to 2011 based on having ICD-9-CM diagnostic codes, which were assigned by neurologists, and being prescribed PD medication. Annual incidence and prevalence were calculated, and time-trend analyses were estimated assuming a Poisson distribution.Results: Over the study period, 19,302 patients in 2004 and 41,606 patients in 2011 fulfilling the study criteria for PD were included in the analysis. The average age-standardized prevalence of PD per 100,000 of population was 84.8 in 2004 and 147.7 in 2011, with a 7.9% yearly increase. Increasing prevalence trends of PD were statistically significant (p < 0.001) in all age groups, with the steepest rate among those aged ≥ 80 years. In contrast, the average age-standardized incidence of PD decreased steadily from 35.3 per 100,000 in 2005 to 28.8 per 100,000 in 2011. The incidence rate was higher in men than in women, and increased with age.Conclusion: We identified an increasing trend in the annual prevalence rates of PD from 2004 to 2011; however, the substantial decline in the incidence of PD suggests that some major environmental risk factors for PD were removed from this population during this time period. [ABSTRACT FROM AUTHOR]

Aims: To analyse time trends of antihyperglycaemic therapy and glycaemic control in adult subjects with type 1, or type 2 diabetes between 2002 and 2014 in Germany/Austria.Methods: 184,864 adults with diabetes (35,144 type 1 diabetes (T1D), 149,720 type 2 diabetes (T2D)) from the DPV-database documented between 2002 and 2014 were included. Regression models were applied for antihyperglycaemic therapy in T2D (non-pharmacological, OADs only, insulin±OADs), insulin therapy in T1D (CT, ICT, CSII) and T2D (BOT, SIT, CT, ICT, CSII), for the use of insulin analogues, and for glycaemic control (HbA1C, severe hypoglycaemia), adjusting for confounders sex, age, and diabetes duration.Results: In T1D, CT (2002:19.7%; 2014:16.0%) and ICT (2002:66.8%; 2014:52.4%) decreased, while CSII increased from 13.5% to 31.5%. In T2D, non-pharmacological treatment became less frequent (2002:36.0%, 2014:21.8%), the use of OADs (2002:19.3%, 2014:28.9%) and insulin±OADs (2002:44.6%, 2014:49.4%) increased. BOT increased from 7.9% to 18.9%, SIT decreased from 12.0% to 8.3%. ICT slightly increased (2002:44.0%, 2014:45.3%), CT decreased (2002:35.8%, 2014:27.2%). Insulin analogues were used more frequently in T1D (rapid-acting:2002:46.8%, 2014:84.8%; long-acting:2002:26.0%, 2014:54.8%) and in T2D (rapid-acting:2002:26.0%, 2014:43.5%; long-acting:2002:13.7%, 2014:53.6%). Until 2011, HbA1C increased in T1D and T2D, but then decreased again. High variability in the rate of hypoglycaemia was observed.Conclusions: This observational study indicates an increased use of insulin pumps in T1D. In T2D, non-pharmacological therapy decreased, and insulin therapy, particular as BOT, rose. An increase in the use of rapid- and long-acting insulin analogues was present in both patient-groups. Time trend was less clear in glycaemic control. [ABSTRACT FROM AUTHOR]

Background: Increased use of lethal suicide methods can have a profound impact on overall suicide incidence; the epidemic of suicide by barbecue charcoal gas poisoning in some East Asian countries is a recent example. There have been concerns about recent rises in suicide using gases in some Western countries.Methods: We investigated suicide by gassing in Hong Kong (2005-2013) using Coroner's files data. The characteristics were compared between suicide by helium inhalation, charcoal gas poisoning, and other methods.Results: About one sixth (1407/8445, 16.7%) of all suicides used gases. Charcoal-burning suicides constituted the majority (97.5%) of them but showed a reduction over the 9-year period (-33%). Helium suicide was not recorded in 2005-2010 but increased from one in 2011 to three in 2012 and 11 in 2013, accounting for 1.2% of all suicides in 2013. Similar to the profile of charcoal-burning suicides, helium suicides were younger and more likely to have debt problem and less likely to receive psychiatric treatment than other suicides. Internet involvement related to the method was found in one third of cases of helium suicide.Limitations: The small number of helium suicides (n=15) limits the power to examine their characteristics.Conclusion: Suicide by charcoal burning showed a downward trend whilst there was an alarming increase in helium suicide in Hong Kong. Public health measures to prevent an epidemic of helium suicide similar to that of charcoal-burning suicide may include close monitoring of trend, responsible media reporting, and restricting online information about and access to this method. [ABSTRACT FROM AUTHOR]

In 2005, 15 years after the introduction of the diagnosis in DSM-III, a telephone survey in Germany revealed that the public was still unfamiliar with the term bipolar disorder. Only 5.3% of those questioned knew at the time that it denotes a mental illness. In the meantime, efforts have been made to spread the concept among the public. In the media there has been increasing mention of the disorder. Another telephone survey in 2017 showed that familiarity with the diagnostic term has grown substantially. 54.0% of respondents now connected the term bipolar disorder with a mental illness. [ABSTRACT FROM AUTHOR]

Run order considerations for two-level full and fractional factorial designs have been studied in depth, but are lacking for Plackett and Burman designs. We look at the level change problems in Plackett and Burman designs. When a systematic run order is appropriate (as opposed to the conventional random run order), minimizing level changes implies the minimization of experiment costs. We thus aim to find optimal run orders with respect to minimizing level changes. It is shown that level changes are a constant for saturated Plackett and Burman designs. Methods for obtaining the minimum/maximum level changes are given. Tables with example run orders for the cases where N = 12 and N = 20 are tabulated for practical uses. By finding minimum level change designs, we also produce maximum level change designs and such results can be directly extended to Trend Robust designs. [ABSTRACT FROM AUTHOR]

Background: Over the past few decades, the incidence of thyroid cancer has dramatically increased in many countries. This increase was mainly seen in papillary cancer. The role of diagnostic practices and the effects of other risk factors were suggested to explain this increase. We provide a descriptive analysis in terms of changes in incidence, geographical distribution, and survival to check the relevance of assumptions about the increase. Methods: A detailed analysis of changes in incidence recorded in French cancer registries between 1982 and 2010 was performed taking into account age, period, and birth cohort. The geographical distribution of the incidence in the 2006-2010 period was estimated from the standardized incidence ratios. The net survival was estimated to evaluate the effects of sex, age, and period of diagnosis in patients diagnosed between 1989 and 2004 and followed-up until 2013. Results: The incidence of papillary cancer has increased sharply over the 1982-2010 period; the average annual rate of increase was 7.8% in men and 7.2% in women. The increase has slowed in the recent period in people aged less than 50 at the time of diagnosis. It has also slowed in the cohorts born 1945 and after. There was a strong geographic disparity in incidence between areas covered by cancer registries. Finally, the net survival was very high; the 10-year net survival was 96% and improved progressively from 82% in patients diagnosed between 1989 and 1993 to 95% in those diagnosed between 1999 and 2004. Conclusion: The increased incidence results most probably from the effect of medical practice, although other risk factors seem also involved, but to a lesser extent. The increase seems to have slowed down in the recent years, especially in the youngest age groups. This observation suggests a recent trend towards saturation of the effects of medical practices in post-1945 cohorts associated with an effect of the gradual dissemination of the recommendations relative to the management of thyroid nodules. [ABSTRACT FROM AUTHOR]

Detecting statistically significant trends in incidence with cancer registries data not only depends on the size of their covered population but also on the levels of incidence rates, duration of diagnostic period and type of temporal variation. We simulated sample sizes of newly diagnosed cases based on a variety of plausible levels of cancer rates and scenarios of changing trends over a period of about 30 years. Each simulated set of cases was then analysed with joinpoint regression models. The power was derived as the relative frequency of the simulation runs where the p -value of the coefficient was less than 0.05 under the alternative model. In case of a decreasing trend with no change of direction (join), an Annual Percentage Change ( APC ) of 1% for an average rate of 10 per 100,000 is detectable in populations of half a million inhabitants or more with a nominal power of 80%. In a model with one joinpoint followed by an increasing trend, the minimum detectable APC increases, and an APC of about 2%, can be detected only with populations of at least 2 million. For analyses requiring a larger sample size than the actual covered population, alternative organisational strategies should be considered, such as an extension of population coverage or data pooling and merging from registries with comparable data. (i.e. when heterogeneity across merging registries is low or acceptable for the specific study question). [ABSTRACT FROM AUTHOR]

In Finland, consumption of Baltic fatty fish may lead to high exposure to persistent organic pollutants (POPs), which might have hazardous health effects. Monitoring of POPs in Baltic fish enables the health authorities to keep dietary advice on fish consumption up to date. In this study, which is a compilation of analytical data from earlier studies, time trends and congener profiles of polychlorinated dioxins and furans (PCDD/Fs) and biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs) in Baltic herring are reported. Altogether 344 samples of Baltic herring from 1978-2009 were collected across the Finnish coast of the Baltic Sea. The chemical analysis was performed in an accredited testing laboratory with high resolution gas chromatography mass spectrometry. During the 31-year period, PCDD/F and PCB concentrations decreased on approximately 80%, from approximately 20 to 5pg/gfw, expressed as WHO2005 TEQ. The PBDE concentrations experienced a 4-10 fold increase during late 1980s-early 1990s, and declined to 1978s levels of approximately 2ng/gfw by 2009. The current concentrations of PCDD/Fs, PCBs and PBDEs in Baltic herring are relatively low, and mostly below EU maximum accepted levels, and are expected to continue decreasing. In the future, it may be possible to re-evaluate the consumption restrictions for this specific Baltic fatty fish. [ABSTRACT FROM AUTHOR]

Objective The examination of lung cancer by histology type is important for monitoring population trends that have implications for etiology and prevention, screening and clinical diagnosis, prognosis and treatment. We provide a comprehensive description of recent histologic lung cancer incidence rates and trends in the USA using combined population-based registry data for the entire nation. Materials and methods Histologic lung cancer incidence data was analyzed from CDC's National Program of Cancer Registries (NPCR) and the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) Program. Standardized rates and trends were calculated for men and women by age, race/ethnicity, and U.S. Census region. Rate ratios were examined for differences in rates between men and women, and annual percent change was calculated to quantify changes in incidence rates over time. Results Trend analysis demonstrate that overall rates have decreased, but incidence has remained stable for women aged 50 or older. Adenocarcinoma and squamous cell carcinoma were the two most common histologic subtypes. Adenocarcinoma rates continued to increase in men and women, and squamous cell rates increased in women only. All histologic subtype rates for white women exceeded rates for black women. Histologic rates for black men exceeded those for white men, except for small cell carcinoma. The incidence rate for Hispanics was nearly half the rate for blacks and whites. Conclusion The continuing rise in incidence of lung adenocarcinoma, the rise of squamous cell cancer in women, and differences by age, race, ethnicity and region points to the need to better understand factors acting in addition to, or in synergy with, cigarette smoking that may be contributing to observed differences in lung cancer histology. [ABSTRACT FROM AUTHOR]

Background/objectives Hemorrhagic stroke is a rare but serious complication after an acute myocardial infarction (AMI). The aims of our study were to establish the incidence, time trends and predictors of risk for hemorrhagic stroke within 30 days after an AMI in 1998-2008. Methods We collected data from the Register of Information and Knowledge about Swedish Heart Intensive Care Admissions (RIKS-HIA). All patients with a myocardial infarction 1998-2008 were included, n = 173,233. The data was merged with the National Patient Register in order to identify patients suffering a hemorrhagic stroke. To identify predictors of risk we used Cox models. Results Overall the incidence decreased from 0.2% (n = 94) in 1998-2000 to 0.1% (n = 41) in 2007-2008. In patients with ST-elevation myocardial infarction the corresponding incidences were 0.4% (n = 76) in 1998-2000 and 0.2% (n = 21) in 2007-2008, and after fibrin specific thrombolytic treatment 0.6% and 1.1%, respectively, with a peak of 1.4% during 2003-2004. In total 375 patients (0.22%) suffered a hemorrhagic stroke within 30 days of the AMI. The preferred method of reperfusion changed from thrombolysis to percutaneous coronary intervention (PCI). Older age (hazard ratio (HR) > 65- ≤ 75 vs ≤ 65 years 1.84, 95% confidence interval (CI) 1.38-2.45), thrombolysis (HR 6.84, 95% CI 5.51-8.48), history of hemorrhagic stroke (HR 12.52, CI 8.36-18.78) and prior hypertension (HR 1.52, CI 1.23-1.86) independently predicted hemorrhagic stroke within 30 days. Conclusions The rate of hemorrhagic stroke within 30 days of an AMI has decreased by 50% between 1998 and 2008. The main reason is the shift in reperfusion method from thrombolysis to PCI. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To analyse the hysterectomy rates (HR) temporal trends for gynecological benign conditions in Lombardy, Northern Italy. Study design: Since 1991, discharges from public or private hospitals have been registered in a standard form (Lombardy Region registry). Women aged ≥20 years, residing in Lombardy, who underwent hysterectomy for benign conditions, were included in the study. Admissions were codified according to the ICD-9 and ICD-10. HRs per 1000 women residing in Lombardy, of the same age class, were computed. Results: In 1996–2010, 143,045 hysterectomies were performed for benign indications. HR showed a declining trend (average annual percent change (AAPC) −2.9), mainly due to the falling number of total abdominal hysterectomies (AAPC −5.3). The most remarkable decrease was seen in women aged 45–54 years (HR 8.05 in 1996 and 4.83 in 2010). Leiomyoma was the most frequent indication in women aged <55 years, whereas in older patients it was uterine prolapse. Conclusions: In 1996–2010, the frequency of hysterectomy in Lombardy fell markedly. This study confirms the declining trend in abdominal hysterectomies observed in most developed countries, though the surgical approaches to hysterectomy differ in different countries. In particular, in Lombardy the proportion of laparoscopically assisted vaginal hysterectomies, though increasing, is low. [Copyright &y& Elsevier]

Abstract: Background: Testicular cancer mainly affects White Caucasian populations, accounts for 1% of all male cancers, and is frequently the most common malignancy among young adult men. In light of the escalating rates of testicular cancer incidence in Europe, and in support of future planning to ensure optimal care of patients with what can be a curable disease, we predict the future burden in 40 European countries around 2025. Methods: Current observed trends were extrapolated with the NORDPRED model to estimate the future burden of testicular cancer in the context of changes in risk versus changes in demographics. Findings: Despite substantial heterogeneity in the rates, the vast majority of European countries will see an increasing burden over the next two decades. We estimate there will be 23,000 new cases of testicular cancer annually in Europe by 2025, a rise of 24% from 2005. Some of the most rapid increases in testicular cancer are observed in Croatia, Slovenia, Italy and Spain, and a transition is underway, whereby recent attenuations and declines in rates in certain high-risk countries in Northern Europe contrast with the increasing trends and escalating burden in Southern Europe. According to our estimates for 2025, around one in 100 men will be diagnosed with the disease annually in the highest risk countries of Europe (Croatia, Slovenia and Norway). Interpretation: Elucidating the key determinants of testicular cancer and the equitable provision of optimal care for patients across Europe are priorities given the steady rise in the number of patients by 2025, and an absence of primary prevention opportunities. Funding: None. [Copyright &y& Elsevier]

Highlights: [•] In the open sea, PCB sediment concentrations significantly decreased from 1991 to 2010. [•] In the estuary, no significant decrease of the PCB sediment concentrations was found. [•] Indirect secondary inputs are the main sources of PCBs in our study area. [ABSTRACT FROM AUTHOR]

Abstract: Polychlorinated dibenzo-p-dioxin/furans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs) were measured in 954 and 539 human serum samples obtained, respectively, from incinerator workers and residents living near and far from municipal solid waste incinerators (MSWIs) during a 10-year period from 2001 to 2011 in Seoul, Korea. The mean toxic equivalent (TEQ) concentrations of PCDD/Fs and DL-PCBs were 9.29 and 5.39pgTEQ/g lipid, respectively. All populations exhibited similar concentrations and profiles, and 2,3,4,7,8-PeCDF, 1,2,3,7,8-PeCDD, and PCB126 were identified as major contributors to TEQs. However, the levels of PCDD/Fs and DL-PCBs were found to have positive associations with age when considering stratified age groups and showed a slight trend toward reduction. Differences in concentrations of these compounds among age groups slightly but continuously decreased from 2001 to 2011. The measured PCDD/F levels were compared to the predicted concentrations by using a single-compartment pharmacokinetic model on the basis of the daily intake of PCDD/Fs. The predicted concentration was 5.24pgTEQ/g lipid, which was approximately half of the measured concentration, reflecting the present exposures. These results suggest that current data on the levels of PCDD/Fs in foodstuffs might be useful to predict the future levels of dioxins in humans, which are expected to decline with time. [Copyright &y& Elsevier]