Twenty-year changes of adolescent mental health and substance use: a Finnish population-based time-trend study.

This time-trend study assesses changes in mental health and substance use among Finnish adolescents from 1998 to 2018. Representative samples of adolescents (N = 6,600) aged 13-16 years participated in school-based, almost identical cross-sectional studies in 1998 (n = 1,446), 2008 (n = 2,009), 2014 (n = 1,800) and 2018 (n = 1,345), respectively. The Strengths and Difficulties Questionnaire was used to assess mental health. When comparing mental health in the clinical range between 1998 and 2018, the main finding was the significant increase of emotional symptoms among females. The percentage of females in the clinical range increased from 17.5 to 30.1% during the twenty-year period. When psychopathology measures were analyzed as continuous variables, the finding of increased emotional problems was confirmed. The study clearly illustrates a linear trend, with a consistent increase in emotional problems among females and decrease in substance use among both genders. An alarming finding of steady increase of self-reported emotional problems indicates the importance of early detection and evidence-based interventions for adolescent with anxiety and depression to prevent adversities associated with these disorders.

Leprosy in Spain: A Descriptive Study of Admissions at Fontilles Sanatorium between 1909 and 2020.

BACKGROUND: The study aimed to characterize patients with leprosy admitted to Fontilles throughout the 20th and 21st centuries, focusing on differences across three periods (I, II, and III). It also explored variables linked to patient survival. METHODS: This was a retrospective descriptive study analyzing the medical records of Fontilles patients from 1909 to 2020. It assessed 26 clinical, sociodemographic, and temporal variables (n = 2652). RESULTS: Most patients were male, single, multibacillary (MB), and farmers, from Andalusia and the Valencian Community. The origin of patients shifted over time towards being mostly foreign-born in period III. More than a half were previously admitted and had family members with leprosy. While leprosy reactions decreased over time, neurological symptoms were increasingly diagnosed. The age at onset, admission, and death increased progressively over time. The survival of patients with leprosy at Fontilles depended on the age at admission and the period. CONCLUSIONS: Improved knowledge, services, and awareness regarding leprosy led to increased age at onset and more favorable outcomes. The prolonged time between symptom onset and diagnosis indicates that leprosy is still a neglected disease. Although MB forms are more severe, leprosy classification did not significantly impact the survival rates of patients at Fontilles.

Trends of mortality from epilepsy in the United States, 1979-2021.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Trends in severe postpartum haemorrhage among nulliparous women with spontaneous onset of labour: A population-based cohort study.

OBJECTIVE: To investigate the incidence of severe postpartum haemorrhage among nulliparous women with a spontaneous onset of labour at term from 2000 to 2020. DESIGN: Population-based cohort study. SETTING: National, using the Medical Birth Registry of Norway. POPULATION: Women (n = 330 244) who gave birth to their first singleton child in a cephalic presentation after a spontaneous onset of labour at term. METHODS: Cross-tabulations and regression analysis with generalised linear models were used to assess time trends and adjust for potential confounding factors. We also stratified the analyses by maternal age groups, obstetric interventions, mode of delivery and institution size. Time trends were analysed using periods of 5 or 6 years as a unit, and the period from 2000 to 2004 was used as the reference. MAIN OUTCOME MEASURES: Severe postpartum haemorrhage (PPH) was defined as blood loss of >1500 mL within 24 h and/or in combination with blood transfusion. RESULTS: Severe PPH occurred in 7601/330 244 (2.30%) women. The incidence increased from 1.24% in 2000-2004 to 3.83% in 2015-2020 (adjusted relative risk, aRR 2.90; 95% CI 2.70-3.12). Changes in maternal characteristics or obstetric interventions did not explain the increase, and we found similar increases across institutions of all sizes. CONCLUSIONS: The incidence of severe PPH among nulliparous women increased almost threefold over 21 years. The current high incidence warrants urgent efforts to assess unknown risk factors, the health care provided and health system factors that may contribute to the increase, to inform improvements in care.

Chronic Pancreatitis in a Large Developing Country: Temporal Trends of Over 64,000 Hospitalizations from 2009 to 2019.

BACKGROUND/OBJECTIVES: Chronic pancreatitis (CP) is a progressive inflammatory disorder associated with marked morbidity and mortality and frequently requires hospitalization. This study aimed to investigate the time trends and geographical distribution of hospital admissions, the lethality rate of CP across Brazil, and the potential relationship with social indicators and associated risk factors. METHODS: Data were retrospectively obtained from the Brazilian Public Health System Registry between January 2009 and December 2019. The prevalence and lethality rates of CP per 100,000 inhabitants in each municipality were estimated from hospitalizations to in-hospital deaths and classified by age, sex, and demographic features. RESULTS: During the study period, 64,609 admissions were retrieved, and most of the patients were males (63.54%). Hospitalization decreased by nearly half (-54.68%) in both sexes. CP rates in males were higher in all age groups. The greatest reduction in admissions (- 64%) was also noted in patients ≥ 70y. CP In-hospital lethality remained stable (5-6%) and similar for males and females. Patients ≥ 70y showed the highest lethality. The greatest increase in CP lethality rates (+ 10%) was observed in municipalities integrated into metropolises, which was mainly driven by small-sized municipalities (+ 124%). CONCLUSIONS: CP hospitalizations decrease in both urban and rural areas, particularly in the North, Northeast, and Central-West regions, and in those above 70 years of age, but are not correlated with lethality rates in the South. This suggests ongoing changes in the environmental and socioeconomic factors in Brazil.

Time trend analysis of rare cancer incidence 2011-2018: Nationwide population-based cancer registries in Japan.

Rare cancers collectively account for a significant proportion of the overall cancer burden in Japan. We aimed to describe and examine the incidence of each rare cancer and the temporal changes using the internationally agreed rare cancer classification. Cancer cases registered in regional population-based cancer registries from 2011 to 2015 and the National Cancer Registry (NCR) from 2016 to 2018 were classified into 18 families, 68 Tier-1 cancer groupings, and 216 single cancer entities based on the RARECAREnet list. Crude incidence rates and age-standardized incidence rates (ASR) were calculated for Tier-1 and Tier-2 cancers. The annual percent change and the 95% and 99% confidence limits for annual ASR for each of the 68 Tier-1 cancers were estimated using the log-linear regression of the weighted least squares method. The differences in ASRs between 2011 and 2018 were evaluated as an absolute change. A total of 5,640,879 cases were classified into Tier-1 and Tier-2 cancers. The ASRs of 18 out of 52 Tier-1 cancers in the rare cancer families increased, whereas the ASR for epithelial tumors of gallbladder decreased. The ASRs of 6 out of the 16 Tier-1 cancers in the common cancer families increased, whereas those of epithelial tumors of stomach and liver decreased. There was no significant change in the incidence of the other 40 Tier-1 cancers. The incidence of several cancers increased due to the dissemination of diagnostic concepts, improved diagnostic techniques, changes in coding practice, and the initiation of the NCR.

Mortality trend of ischemic heart disease (2008-2022): A retrospective analysis of epidemiological data.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Incidence, mortality and survival rates of lip, oral cavity and salivary glands cancers in Singapore: A half-century time trend analysis (1968-2017).

OBJECTIVES: To examine trends in incidence and mortality and evaluate overall survival (OS) of oral cancer in Singapore between 1968 and 2017. METHODS: All diagnosed oral cancers by anatomical sites and population size were extracted from the Singapore Cancer Registry and the Department of Statistics Singapore. The trend of age-standardized incidence rate (ASIR) and mortality rate (ASMR) (per 100 000 person-years) of the lip, oral cavity and salivary gland cancers were evaluated by Prais-Winsten regressions for each ethnicity and gender. Kaplan-Meier curves were performed to evaluate the OS by anatomical sites in each age group by ethnicity and sex. RESULTS: Overall, 49, 3494 and 1066 people were diagnosed, and 28, 2310 and 476 died from lip, oral cavity and salivary gland cancers, respectively. The oral cavity cancer ASIR and ASMR reduced from 3.07 (1968-1972) to 2.01(2008-2012) and from 2.06 (1978-1982) to 1.21 (2013-2017) per 100 000 person-years, respectively, with both highest in Indians throughout the whole period. Male:Female ratio ranged from 3.43 (1973-1977) to 1.75 (2013-2017) and from 3.41 (1978-1982) to 2.40 (2013-2017) for ASIR and ASMR, respectively. However, both salivary gland cancer ASIR and ASMR increased from 0.50 (1968-1972) to 0.80 (2008-2012) and from 0.18 (1968-1982) to 0.42 (1988-1992) per 100 000 person-years, respectively, with both higher in males since 1993. Oral cavity cancer ASIR decreased for males aged ≥60, and Indian females ≥25, but increased among Chinese females aged ≥60. Oral cavity cancer ASMR decreased among Chinese aged 25-59, and among Malay males and Indian females. Salivary gland cancer ASIR increased among Chinese males aged ≥60 and Malay males aged 25-59; while ASMR increased among Chinese males aged ≥60. The median OS for oral cavity, lip and salivary gland cancers were 3.0, 9.3 and 18.1 years, respectively, with females surviving longer than males. CONCLUSIONS: Singapore has experienced a decline in the incidence and mortality of lip, oral cancer, an increase in in the incidence and mortality of salivary gland cancer, with an increase in the median overall survival rate. Monitoring the magnitude of oral cancer burden and the demographic, and temporal variations is necessary for tailoring health planning and setting priorities for future clinical care and research.

Sex-specific trends in incidence of first myocardial infarction among people with and without diabetes between 1985 and 2016 in a German region.

BACKGROUND: The reduction of myocardial infarction (MI) and narrowing the gap between the populations with and without diabetes are important goals of diabetes care. We analyzed time trends for sex-specific incidence rates (IR) of first MI (both non-fatal MI and fatal MI) as well as separately for first non-fatal MI and fatal MI in the population with and without diabetes. METHODS: Using data from the KORA myocardial infarction registry (Augsburg, Germany), we estimated age-adjusted IR in people with and without diabetes, corresponding relative risks (RR), and time trends from 1985 to 2016 using Poisson regression. RESULTS: There were 19,683 people with first MI (34% fatal MI, 71% men, 30% with diabetes) between 1985 and 2016. In the entire study population, the IR of first MI decreased from 359 (95% CI: 345-374) to 236 (226-245) per 100,000 person years. In men with diabetes, IR decreased only in 2013-2016. This was due to first non-fatal MI, where IR in men with diabetes increased until 2009-2012, and slightly decreased in 2013-2016. Overall, fatal MI declined stronger than first non-fatal MI corresponding to IRs. The RR of first MI substantially increased among men from 1.40 (1.22-1.61) in 1985-1988 to 2.60 (2.26-2.99) in 1997-2000 and moderately decreased in 2013-2016: RR: 1.75 (1.47-2.09). Among women no consistent time trend for RR was observed. Time trends for RR were similar regarding first non-fatal MI and fatal MI. CONCLUSIONS: Over the study period, we found a decreased incidence of first MI and fatal MI in the entire study population. The initial increase of first non-fatal MI in men with diabetes needs further research. The gap between populations with and without diabetes remained.

Modifiable risk factors of inequalities in hypertension: analysis of 100 million health checkups recipients.

Inequalities in health behaviors are thought to contribute to inequalities in hypertension. This study examined the extent to which modifiable mediating factors explain income inequalities in hypertension. This repeated cross-sectional study used data from National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) from 2009 to 2015. Those aged between 40 and 74 were enrollees in the Specific Health Checkups. Hypertension was defined as systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90, or the use of antihypertensive medication. The mediating effects of exercise, obesity, smoking, and alcohol drinking on the association between income, as an indicator of SES, and hypertension were determined by the Karlson-Holm-Breen (KHB) method. The mean age of the 68,684,025 men and 59,118,221 women was 54.7 (SD = 9.6) and 56.7 (SD = 10.0) years, respectively. Prevalence of hypertension was higher in the lowest income group (48.6% for men, 40.2% for women) than in the highest income group (33.3% for men, 21.5% for women). Inequalities tended to increase over time. Inequalities were larger among those who did not use antihypertensive medication. Modifiable risks explained 10.6% of the association between income and hypertension for men and 15.1% for women. In men, drinking and obesity explained 8.8% and 5.5% of the inequalities in hypertension, respectively. In women, obesity explained 18.8%. Exercise increased the proportion mediated over time. Smoking explained 5.5% among women taking antihypertensive medication. There were health inequalities in hypertension among Japanese adults, and the modifiable risk factors partially explained the inequalities.

Lead, cadmium, and mercury blood levels in schoolchildren in southern Sweden: Time trends over the last decades.

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.

Prevalence and Cost of Antipsychotic Prescribing, within the Context of Psycholeptic Prescribing, in the Irish Setting.

Psycholeptic and specifically antipsychotic prescribing is increasing worldwide each year. This study aims to investigate the prevalence and cost of antipsychotic prescribing, within the wider frame of psycholeptic prescribing, in the Irish context. Quantitative analysis of a dataset from the Primary Care Reimbursement Service relating to cost and prescribing frequency of ATC Class N05 psycholeptic drugs from January 2020-August 2022 inclusive was conducted using Microsoft® Excel® for Microsoft 365 MSO (Version 2311) and STATA 18. Descriptive statistics and time-trend regression analysis were used to investigate the prescribing prevalence of psycholeptics and antipsychotics licensed for use in the Republic of Ireland, and the total cost per funding scheme. The prevalence of psycholeptic prescribing increased yearly from 2020-2022, peaking at 328,572 prescriptions in December 2020 with a total cost of psycholeptic drugs to the State in 2021 of €57,886,250, which was 0.5% of an increase on 2020. Over the 32-month time period, the average monthly cost of psycholeptic drugs was €4,436,469 on the General Medical Services (GMS) scheme and €369,154 on the Drug Payment Scheme (DPS). In 2021, quetiapine, olanzapine, and risperidone were the most prescribed antipsychotics, accounting for 66.58% of antipsychotics prescribed on the GMS scheme. This study identified the large expenditure on psycholeptics and antipsychotics in Ireland, with a higher proportion of the Irish healthcare budget spent on antipsychotics than that of the UK and the USA. The development of Irish antipsychotic prescribing guidelines may allow for structured, cost-effective prescribing.

Concentrations of 45 Per- and Polyfluoroalkyl Substances in North American River Otters (Lontra canadensis) from West Virginia, USA.

North American river otters (Lontra canadensis) are top predators in riverine ecosystems and are vulnerable to per- and polyfluoroalkyl substance (PFAS) exposure. Little is known about the magnitude of exposure and tissue distribution of PFAS in river otters. We measured 45 PFAS in various tissues of 42 river otters collected from several watersheds in the state of West Virginia, USA. The median concentrations of ∑All (sum concentration of 45 PFAS) varied among tissues in the following decreasing order: liver (931 ng/g wet weight) > bile > pancreas > lung > kidney > blood > brain > muscle. Perfluoroalkylsulfonates (PFSAs) were the predominant compounds accounting for 58-75% of the total concentrations, followed by perfluoroalkyl carboxylates (PFCAs; 21-35%). 8:2 fluorotelomer sulfonate (8:2 FTS), 10:2 FTS, and 6:2 chlorinated polyfluoroalkyl ether sulfonate were frequently found in the liver (50-90%) and bile (96-100%), whereas hexafluoropropylene oxide dimer acid (HFPO-DA) was rarely found. The hepatic concentrations of ∑All in river otters collected downstream of a fluoropolymer production facility located along the Ohio River were 2-fold higher than those in other watersheds. The median whole body burden of ∑All was calculated to be 1580 µg. PFOS and perfluorooctanoic acid (PFOA) concentrations in whole blood of some river otters exceeded the human toxicity reference values, which warrant further studies.

Body dissatisfaction and dieting among Finnish adolescents: a 20-year population-based time-trend study.

Body image has an important role in the health and development of adolescents. Body dissatisfaction and dieting can become chronic and continue into adulthood. There is a lack of recent, comprehensive studies on ongoing trends on body dissatisfaction. This study assessed time-trend changes in self-reported body dissatisfaction and dieting among Finnish adolescents at four assessment points. Representative samples of adolescents (N = 6660) aged 13-16 years participated in school-based, cross-sectional studies in 1998 (N = 1458), 2008 (N = 2044), 2014 (N = 1809), and 2018 (N = 1349), respectively. The studies were similar in design, methodology, and geographical recruitment areas. Body dissatisfaction and dieting were assessed with a questionnaire including items derived from the DSM-IV criteria for anorexia and bulimia nervosa. From 1998 to 2018, dieting and fears related to gaining weight decreased among females. Body dissatisfaction reduced among females, and their wishes to become thinner became less prevalent. Consuming large amounts of food at one time consistently decreased among females and males and there were no changes in the rates of willful vomiting. The number of females in the 90th percentile with the most severe symptoms decreased. The results indicate that body dissatisfaction and disturbed dieting improved among females during the 20-year study. Despite these positive developments, the overall level of symptoms among females remained substantial, indicating that females have much higher levels of body dissatisfaction and dieting than males.

Social anxiety in Finnish adolescents from 2013 to 2021: change from pre-COVID-19 to COVID-19 era, and mid-pandemic correlates.

PURPOSE: Social anxiety disorder (SAD) is prevalent in adolescents. Increase in levels of general anxiety since 2010's has been observed in young people. Little is known of time trends in symptoms of social anxiety during 2010's, of pre- to during-COVID-19 era changes, or of associations between social anxiety symptoms and pandemic severity, distance education, and COVID-19-related experiences in young people. METHODS: We examined social anxiety symptoms, their temporal changes, and their associations with COVID-19 related factors in a sample of 450 000 13-to-20-year-old Finns in 2013-2021. Data from nationwide School Health Promotion study was used. Social anxiety symptoms were assessed with the Mini-SPIN using cut-off score ≥ 6 as indicator of high social anxiety. Multivariate logistic regression analyses were used, controlling for gender, age, family SES, and symptoms of general anxiety and depression. RESULTS: High-level social anxiety symptoms increased markedly from 2013/2015 to 2021 among both sexes. A steeper increase was found among females. In 2021, 47% of females self-reported high social anxiety, a two-fold increase relative to 2013/2015. No association between regional COVID-19 incidence and change in social anxiety symptoms was found. No clear associations between time spent in distance education and social anxiety symptoms were found. Fears of getting infected or transmitting coronavirus, and reports of not getting needed support for schoolwork during distance education were all associated with high social anxiety. CONCLUSION: Prevalence of high social anxiety in young people aged 13-20 has increased considerably from 2013 to 2021, especially among girls. During COVID-19 pandemic, socially anxious young people report a need for educational support and suffer from infection-related fears.

Sensitization to ethylenediamine dihydrochloride in patients with contact dermatitis in northeastern Italy from 1996 to 2021.

BACKGROUND: Ethylenediamine dihydrochloride is a versatile aliphatic amine found in numerous medications and industrial compounds and is a known sensitiser. The sensitization prevalence is affected by geographical and socio-cultural factors. OBJECTIVES: The objectives are to analyse the temporal trend of sensitization to ethylenediamine dihydrochloride in northeastern Italy and to investigate associations with occupations. METHODS: Between 1996 and 2021, 30 629 patients with suspected allergic contact dermatitis were patch tested with the Triveneto baseline series. Individual characteristics were collected through a standardised questionnaire. RESULTS: The overall prevalence of ethylenediamine dihydrochloride sensitization was 1.29% with percentages similar in both sexes. We observed a significant decreasing trend over time (p < 0.001), yielding a sensitization prevalence <1% in recent years. Among departments, residence in Pordenone area was protective for sensitization. No significant associations were observed with specific occupations. We found significant associations between ethylenediamine dihydrochloride sensitization and being 26-35 years old (odds ratio [OR], 1.47; 95% confidence interval [CI]: 1.05-2.08), and sensitization for many haptens, such as paraben mix (OR, 5.3; 95% CI: 3.3-8.5), epoxy resin (OR, 5.1; 95% CI: 3.0-8.7), neomycin sulphate and mercaptobenzothiazole. CONCLUSIONS: Our study showed a downward time trend of ethylenediamine dihydrochloride sensitization in northeastern Italian population and pointed to an update of the Triveneto baseline series.

Factors determining contamination and time trends in cyclic and linear siloxanes in sediments from an industrialized lake in Korea.

Siloxanes, widely used in various consumer and industrial products, are emerging concerns of contaminants. Despite this, limited studies have been conducted on contamination and time trends on siloxanes in coastal environments. In the present study, four cyclic and 15 linear siloxanes were measured in sediments collected from an artificial saltwater lake in Korea during 2001-2016 to investigate contamination, time trends, and ecotoxicological concerns. Cyclic siloxanes were detected in all sediment samples, whereas linear siloxanes were not frequently detected. The highest siloxane concentrations were observed in creeks passing through various industrial complexes, indicating that industrial activities predominantly contributed to siloxane contamination in coastal environments. Decamethylcyclopentasiloxane (D5) and dodecylcyclohexasiloxane (D6) were predominant siloxanes in sediments over the last two decades. Siloxane concentrations significantly increased in creek sediments from 2008 to 2016, whereas those in inshore and offshore regions significantly decreased due to a strong dilution effect by the operation of tidal power plant. This suggests that consumption patterns and coastal development activities are crucial factors determining the contamination and time trends in the sedimentary siloxanes. The sedimentary concentrations of octamethylcyclotetrasiloxane (D4) and D5 exceeded several thresholds, raising the potentials for ecological risks to aquatic organisms.

MIDAS-2: an enhanced Bayesian platform design for immunotherapy combinations with subgroup efficacy exploration.

Although immunotherapy combinations have revolutionised cancer treatment, the rapid screening of effective and optimal therapies from large numbers of candidate combinations, as well as exploring subgroup efficacy, remains challenging. This necessitates innovative, integrated, and efficient trial designs. In this study, we extend the MIDAS design to include subgroup exploration and propose an enhanced Bayesian information borrowing platform design called MIDAS-2. MIDAS-2 enables quick and continuous screening of promising combination strategies and exploration of their subgroup effects within a unified platform design framework. We use a regression model to characterize the efficacy pattern in subgroups. Information borrowing is applied through Bayesian hierarchical modelling to improve trial efficiency considering the limited sample size in subgroups. Time trend calibration is also employed to avoid potential baseline drifts. Simulation results demonstrate that MIDAS-2 yields high probabilities for identifying the effective drug combinations as well as promising subgroups, facilitating appropriate selection of the best treatments for each subgroup. The proposed design is robust against small time trend drifts, and the type I error is successfully controlled after calibration when a large drift is expected. Overall, MIDAS-2 provides an adaptive drug screening and subgroup exploring framework to accelerate immunotherapy development in an efficient, accurate, and integrated fashion.

Increasing exposure to the UV filters octocrylene and 2-ethylhexyl salicylate in Germany from 1996 to 2020: Human biomonitoring in 24-h urine samples of the German Environmental Specimen Bank (ESB).

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.

Prevalence and experience of dental caries among Singaporean schoolchildren: A time-trend analysis from 2007 to 2019.

OBJECTIVES: This study aimed to describe caries prevalence and experience trends of permanent teeth among Singapore schoolchildren between 2007 and 2019. METHODS: Anonymized records of all 6-year-old Primary 1 (P1), 11-year-old Primary 6 (P6) and 14-year-old Secondary 3 (S3) before the start of each school year were extracted from the Integrated Dental Electronic Assessment System (IDEAS) by school level, ethnicity and sex. Prais-Winsten regression was used to assess trends of mean decayed, missing and filled teeth (DMFT) and caries prevalence (% DMFT > 0) among the schoolchildren by school level, with reported Average Annual Percentage Change (AAPC) together with respective 95% confidence interval (CI). RESULTS: In total, 519 471 P1, 566 573 P6 and 548 138 S3 were included during the above period, and the majority were comprised of Chinese children (P1: 67.2%, P6: 68.8% and S3: 71.0%, respectively). Overall, the prevalence of caries dropped from 6.9% in 2007 to 3.5% in 2019 among P1, from 34.5% in 2009 to 20.3% in 2019 among P6 and from 41.5% in 2007 to 33.5% in 2019 among S3 schoolchildren. The mean DMFT reduced from 0.11 to 0.05 among P1, 0.72 to 0.35 among P6 and 1.05 to 0.76 among S3 schoolchildren during the same period. Caries prevalence and mean DMFT were consistently higher among girls. On average, caries prevalence decreased 5% per year in P1 (AAPC -5.0 [95% CI: -6.1, -3.9]) and P6 (AAPC -4.9 [95% CI: -5.7, -4.1]) and 2% among S3 (AAPC -2.0 [95% CI: -3.5, -0.4]) schoolchildren. Caries prevalence decreased approximately 4% ~ 5% annually among P1 and P6 schoolchildren regardless of ethnicity. The average decrease in caries prevalence was lower (about 2%) among all ethnicities at S3 school level. CONCLUSION: Dental caries in permanent dentition of Singaporean schoolchildren had decreased from 2007 to 2019. However, the decrease observed among primary school students was more than double that among secondary schoolchildren.