Cervical cancer incidence in Denmark: Disentangling determinants of time trend.

Cervical cancer is a preventable disease. Nevertheless, stagnation has been seen in incidence rates also in countries with well-functioning healthcare. On this basis, we investigated associations between control interventions and changes in cervical cancer incidence in Denmark from 2009 to 2022. Data on human papillomavirus (HPV)-vaccination were retrieved from Staten's Serum Institute; on screening recommendations from Danish Health Authority, on screening performance from Danish Quality Database for Cervical Screening; and on cervical cancer incidence from Nordcan and Danish Cancer Register. We reported coverage with HPV vaccination (1+ dose); coverage with cervical cell samples; number of women with primary HPV tests; proportion of non-normal cell samples without timely follow-up; number of conizations; and cervical cancer incidence rates. In 2022, all women aged ≤29 had been offered childhood HPV vaccination with coverage of 80%-90%. By 2020-2022, the cervical cancer incidence rate in women aged 20-29 was 3 per 100,000; at level of disease elimination. In 2017, women aged 70+ were offered a one-time HPV screening, and by 2020-2022, the old-age peak in cervical cancer incidence had largely disappeared. From 2009 to 2022, proportion of non-normal cell samples without timely follow-up decreased from 20% to 10%, and conventional cytology was largely replaced by SurePath liquid-based cytology; these factors could explain the steady decrease in cervical cancer incidence rate. Implementation of primary HPV screening in women aged 30-59 in 2021 was reflected in a, probably temporary, increase in the 2022 cervical cancer incidence rate. In conclusion, combined interventions with childhood HPV vaccination; one-time HPV screening of elderly women; and better management of screening broke previous stagnation in cervical cancer incidence rate.

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.

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.

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.

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.

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.

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.

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.

The incidence of childhood-onset type 1 diabetes, time trends and association with the population composition in Sweden: a 40 year follow-up.

AIMS/HYPOTHESIS: During the 1980s and 1990s, the incidence of childhood-onset type 1 diabetes more than doubled in Sweden, followed by a plateau. In the present 40 year follow-up, we investigated if the incidence remained stable and whether this could be explained by increased migration from countries reporting lower incidences. METHODS: We used 23,143 incident cases of childhood-onset type 1 diabetes reported between 1978 and 2019 to the nationwide, population-based Swedish Childhood Diabetes Registry and population data from Statistics Sweden. Generalised additive models and ANOVA were applied to analyse the effects of onset age, sex, time trends and parental country of birth and interaction effects between these factors. RESULTS: The flattening of the incidence increase seems to remain over the period 2005-2019. When comparing the incidence of type 1 diabetes for all children in Sweden with that for children with both parents born in Sweden, the trends were parallel but at a higher level for the latter. A comparison of the incidence trends between individuals with Swedish backgrounds (high diabetes trait) and Asian backgrounds (low diabetes trait) showed that the Asian subpopulation had a stable increase in incidence over time. CONCLUSIONS/INTERPRETATION: In Sweden, the increase in incidence of childhood-onset type 1 diabetes in the late 20th century has been approaching a more stable albeit high level over the last two decades. Increased immigration from countries with lower incidences of childhood-onset type 1 diabetes does not provide a complete explanation for the observed levelling off.

Trends and future projections of cervical cancer-related outcomes in Japan: What happens if the HPV vaccine program is not implemented?

Contrary to other developed countries, in Japan, recent years have seen increases in cervical cancer incidence and mortality among young people. However, the human papillomavirus (HPV) vaccine program, a key measure for avoiding cervical cancer, has been virtually suspended. Temporal changes in cervical cancer profiles in this unique situation have not been fully investigated epidemiologically. Our study aimed to determine the current status and future trends of the incidence and mortality of cervical cancer and precancerous lesions in Japan. Mortality rates of cervical cancer during 1975 to 2016 and incidence rates of cervical cancer and cervical intraepithelial neoplasia (CIN) 3 during 1975 to 2013 were examined using vital statistics and population-based cancer registry data in Japan. Bayesian age-period-cohort analyses were performed to analyze temporal changes of the three cervical cancer-related outcomes. We also calculated projections to 2028 for the three outcomes, assuming that HPV vaccination coverage and screening rates in Japan would be maintained at the current level after the resumption of the national vaccination program. The risk of occurrence of the three outcomes showed similar changes by birth cohort, peaking in the mid-1890s to 1900s birth cohorts, declining sharply in the 1940s birth cohort, and persistently increasing in the 1950s and later birth cohorts. Projections to 2028 show increases in cervical cancer incidence and mortality in the 30 to 69 age group, with a particular increase in CIN3 incidence in the 25 to 49 age group, if HPV vaccine programs and screening are not effectively implemented. These findings revealed an increasing cervical disease burden among reproductive age females in Japan.

Potential impact of time trend of whole grain intake on burden of major cancers in China.

Numerous studies have revealed associations between high intake of whole grains and reduced risk of various cancers. Yet, in recent decades, the traditional Chinese diets have been challenged by reduction in whole grains and increase in refined grains. To assess the impact of this dietary transition on cancer prevention, we analyzed the time trend of whole grain intake using nationally representative sampling data of over 15 thousand individuals from the China Health and Nutrition Survey. We applied the comparative risk assessment method to estimate the population attributable fraction of cancers due to insufficient whole grain intake from 1997 to 2011 and projected the trend of whole grain intake and the associated burden of cancers to 2035. We found a significant decrease of approximately 59% of whole grain intake in the Chinese population from 1997 to 2011. Compared with 1997, insufficient intake of whole grains was responsible for 9940 more cases of breast cancer, 12,903 more cases of colorectal cancer and 434 more cases of pancreatic cancer in 2011. Our projections suggest that if every Chinese would consume 125 g whole grain per day as recommended by the latest Chinese Dietary Guidelines, 0.63% bladder cancer, 8.98% breast cancer, 15.85% colorectal cancer, 3.86% esophageal cancer, 2.52% liver cancer and 2.22% pancreatic cancer (totaling 186,659 incident cases) could theoretically be averted by 2035. Even if everyone maintained the 2011 whole grain intake level, an estimated 8.38% of cancer events could still be prevented by 2035.

Fluorine Mass Balance, including Total Fluorine, Extractable Organic Fluorine, Oxidizable Precursors, and Target Per- and Polyfluoroalkyl Substances, in Pooled Human Serum from the Tromsø Population in 1986, 2007, and 2015.

Of the thousands of per- and polyfluoroalkyl substances (PFAS) known to exist, only a small fraction (≤1%) are commonly monitored in humans. This discrepancy has led to concerns that human exposure may be underestimated. Here, we address this problem by applying a comprehensive fluorine mass balance (FMB) approach, including total fluorine (TF), extractable organic fluorine (EOF), total oxidizable precursors (TOP), and selected target PFAS, to human serum samples collected over a period of 28 years (1986, 2007, and 2015) in Tromsø, Norway. While concentrations of TF did not change between sampling years, EOF was significantly higher in 1986 compared to 2007 and 2015. The ∑12PFAS concentrations were highest in 2007 compared to 1986 and 2015, and unidentified EOF (UEOF) decreased from 1986 (46%) to 2007 (10%) and then increased in 2015 (37%). While TF and EOF were not influenced by sex, women had higher UEOF compared to men, opposite to target PFAS. This is the first FMB in human serum to include TOP, and it suggests that precursors with >4 perfluorinated carbon atoms make a minor contribution to EOF (0-4%). Additional tools are therefore needed to identify substances contributing to the UEOF in human serum.

The Role of Functional Urban Areas in the Spread of COVID-19 Omicron (Northern Spain).

This study focuses on the space-time patterns of the COVID-19 Omicron wave at a regional scale, using municipal data. We analyze the Basque Country and Cantabria, two adjacent regions in the north of Spain, which between them numbered 491,816 confirmed cases in their 358 municipalities from 15th November 2021 to 31st March 2022. The study seeks to determine the role of functional urban areas (FUAs) in the spread of the Omicron variant of the virus, using ESRI Technology (ArcGIS Pro) and applying intelligence location methods such as 3D-bins and emerging hot spots. Those methods help identify trends and types of problem area, such as hot spots, at municipal level. The results demonstrate that FUAs do not contain an over-concentration of COVID-19 cases, as their location coefficient is under 1.0 in relation to population. Nevertheless, FUAs do have an important role as drivers of spread in the upward curve of the Omicron wave. Significant hot spot patterns are found in 85.0% of FUA area, where 98.9% of FUA cases occur. The distribution of cases shows a spatially stationary linear correlation linked to demographically progressive areas (densely populated, young profile, and with more children per woman) which are well connected by highways and railroads. Based on this research, the proposed GIS methodology can be adapted to other case studies. Considering geo-prevention and WHO Health in All Policies approaches, the research findings reveal spatial patterns that can help policymakers in tackling the pandemic in future waves as society learns to live with the virus.

Prevalence, trends, and individual patterns of long-term antidepressant medication use in the adult Swiss general population.

PURPOSE: Antidepressant use has increased in many European countries, mostly driven by longer treatment duration. The aim of this study was to provide prevalence rates of long-term users of antidepressants for the Swiss population over the last decade and to investigate associated factors for longer use. METHODS: We examined the prevalence rates of individuals with at least one prescription for antidepressants using longitudinal health claims data for 2013 to 2021. We defined short- (< one year), medium- (one-two years), and long-term users (> two years) for 2015 to 2019. We applied a binary logistic regression model to investigate the effects of population (gender, age, area of living, language, health insurance plan, and nursing home) and treatment characteristics (psychiatric or psychotherapeutic care) on long-term compared to short- and medium-term users in 2019. RESULTS: In 2021, 9% of the Swiss population (n = 770,698) received at least one antidepressant prescription, which remained stable since 2013. In 2019, the proportion of long-term users was 57.4%, with steady increase since 2015. The proportion of medium- and short-term users has decreased. Older age, being a woman, living in an urban area, living in a nursing home, being enrolled in a standard care plan, and receiving psychiatric or psychotherapeutic care were factors positively associated with being a long-term user. CONCLUSION: The proportion of long-term users in Switzerland is high and steadily increasing. Given the ongoing debate about the confounding effects of relapse and withdrawal, more research is needed to investigate longer use of antidepressants that could indicate overprescribing.

Feed as a source of polybrominated diphenyl ethers (PBDEs).

One of the most important routes for human exposure to polybrominated diphenyl ethers (PBDEs) is the ingestion of contaminated food. Food of animal origin safety is strongly related to feed quality. The aim of the study was the assessment of feeds and feed materials quality associated with ten PBDE congeners (BDE-28, 47, 49, 99, 100, 138, 153, 154, 183 and 209) contamination. The quality of 207 feed samples divided into eight categories (277/2012/EU) was checked using the gas chromatography-high resolution mass spectrometry (GC-HRMS). At least one congener was identified in 73% of the samples. All investigated fish oil, animal fat, and feed for fish were contaminated, and 80% of plant-origin feed samples were free of PBDEs. The highest median content of ∑10PBDE was found in fish oils (2260 ng kg-1) followed by fishmeal (530 ng kg-1). The lowest median was found in mineral feed additives, plant materials excluding vegetable oil and compound feed. BDE-209 was the most frequently detected congener (56%). All congeners except BDE-138 and BDE-183 were detected in 100% of the fish oil samples. Except for BDE-209, the congener detection frequencies did not exceed 20% in compound feed, feed of plant origin, and vegetable oils. Excluding BDE-209, similar congener profiles were found for fish oils, fishmeal and feed for fish, with BDE-47 in the highest concentration, followed by BDE-49 and BDE-100. Another pattern appeared in animal fat, with a higher median concentration of BDE-99 than BDE-47. Time-trend analysis of PBDE concentrations in fishmeal (n = 75) showed a 63% decrease in ∑10PBDE (p = 0.077) and a 50% decrease in the ∑9PBDE (p = 0.008) between 2017 and 2021. It proves the international legislation implemented to reduce PBDE environmental levels has been effective.

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 demand for ophthalmic pathology: time trends in a laboratory with nationwide coverage.

PURPOSE: To report the time trends in basic patient characteristics and the number of specimens received at a national referral center for ophthalmic pathology. METHODS: Data on patient sex, age at surgical resection and geographical location of the referring unit were obtained for all specimens received at the St. Erik Ophthalmic Pathology laboratory, Stockholm, Sweden, between January 1st, 1959, and December 31st, 2021. RESULTS: A total of 33 057 specimens had been received, of which 14 560 (44%) came from men and 18 477 (56%) from women (for 20 patients, the sex was not specified). The average annual percent change (AAPC) in the number specimens received was + 10.5%, whereas the Swedish population increased with 0.5% per year. Patients became older throughout the period, with an average yearly increase of patient age at surgery of 0.3 years (AAPC 0.2%). Overall, women were three years older than men at surgery (59.4 versus 56.4 years, P < 0.0001) The number of specimens increased with patient age from the first to the 8th decade, after which it decreased to zero in the 11th decade. The largest portion of patients had undergone their surgery in one of the hospitals or clinics in the capital region, with four of the five largest sources corresponding to the most populous counties in the country. CONCLUSIONS: During six decades, the growth in number of specimens sent to our national referral center for ophthalmic pathology has greatly outpaced the growth of the population, indicating an increasing demand for subspecialized services. Throughout the period, patients have become older, and a higher number of specimens have been submitted from female patients.