Analysis of Nonconcurrent Controls in Adaptive Platform Trials: Separating Randomized and Nonrandomized Information.

Adaptive platform trials allow treatments to be added or dropped during the study, meaning that the control arm may be active for longer than the experimental arms. This leads to nonconcurrent controls, which provide nonrandomized information that may increase efficiency but may introduce bias from temporal confounding and other factors. Various methods have been proposed to control confounding from nonconcurrent controls, based on adjusting for time period. We demonstrate that time adjustment is insufficient to prevent bias in some circumstances where nonconcurrent controls are present in adaptive platform trials, and we propose a more general analytical framework that accounts for nonconcurrent controls in such circumstances. We begin by defining nonconcurrent controls using the concept of a concurrently randomized cohort, which is a subgroup of participants all subject to the same randomized design. We then use cohort adjustment rather than time adjustment. Due to flexibilities in platform trials, more than one randomized design may be in force at any time, meaning that cohort-adjusted and time-adjusted analyses may be quite different. Using simulation studies, we demonstrate that time-adjusted analyses may be biased while cohort-adjusted analyses remove this bias. We also demonstrate that the cohort-adjusted analysis may be interpreted as a synthesis of randomized and indirect comparisons analogous to mixed treatment comparisons in network meta-analysis. This allows the use of network meta-analysis methodology to separate the randomized and nonrandomized components and to assess their consistency. Whenever nonconcurrent controls are used in platform trials, the separate randomized and indirect contributions to the treatment effect should be presented.

Down syndrome and associated atrioventricular septal defects in a nationwide Norwegian cohort: Prevalence, time trends, and outcomes.

INTRODUCTION: The prevalence of Down syndrome (DS) is approximately 1 per 1000 births and is influenced by increasing maternal age over the last few decades. DS is strongly associated with congenital heart defects (CHDs), especially atrioventricular septal defect (AVSD). Our objectives were to investigate the prevalence of live-born infants with DS having a severe CHD in the Norwegian population over the last 20 years and compare outcomes in infants with AVSD with and without DS. MATERIAL AND METHODS: Information on all births from January 1, 2000 to December 31, 2019 was obtained from the Medical Birth Registry of Norway. We also obtained data on all infants with severe CHDs in Norway registered in Oslo University Hospital's Clinical Registry for Congenital Heart Defects during 2000-2019 and accessed individual-level patient data from the electronic hospital records of selected cases. Infants with AVSD and DS were compared to infants with AVSD without chromosomal defects. Crude and adjusted odds ratios (ORs) of infant mortality and need for surgery during the first year of life, with associated 95% confidence intervals (CIs), were estimated by logistic regression. RESULTS: A total of 1 177 926 infants were live-born in Norway during the study period. Among these, 1456 (0.1%) had DS. The prevalence of infants with DS having a severe CHDs was relatively stable, with a mean of 17 cases per year. The most common CHD associated with DS was AVSD (44.4%). Infants with AVSD and DS were more likely to have cardiac intervention during their first year of life compared to infants with AVSD without chromosomal defects (adjusted OR [aOR]: 2.52; 95% CI 1.27, 4.98). However, we observed no difference in infant mortality during first year of life between the two groups (aOR: 1.08; 95% CI 0.43, 2.70). CONCLUSIONS: The prevalence of live-born infants with severe CHDs and DS has been stable in Norway across 20 years. Infants with AVSD and DS did not have higher risk of mortality during their first year of life compared to infants with AVSD without chromosomal defects, despite a higher risk of operative intervention.

Time trends in incidence of postpartum depression and depression in women of reproductive age.

BACKGROUND: Little is known about the time trends of postpartum depression (PPD) and whether they differ from time trends of depression among women in general. METHODS: Using Danish health registers, we identified a postpartum population from all women who had a liveborn child from 2000-2022. We sampled a background population by matching five women for each delivery on age and date of childbirth. Depression and PPD were measured as incident depression diagnosis or redeemed antidepressant prescription within 180 days from childbirth/matching. We described incidence rates from 2000-2022 using Poisson regression with a restricted cubic spline. RESULTS: The study population included 1,133,947 postpartum women (669,101 unique), matched to 5,669,735 women (1,165,505 unique). Overall IR per 10,000 person-years of diagnoses was 34.3 (95% CI: 32.8-35.9) for PPD and 18.9 (95% CI: 18.3-19.4) for depression. Both IRs increased similarly over time in the main analyses, but more pronounced for PPD in primiparous and older mothers. Correspondingly, IR for prescriptions was 135.7 (95% CI: 132.7-138.8) for PPD and 209.8 (95% CI: 208.1-211.5) for depression, and both groups had fluctuating time trends. LIMITATIONS: Depression measures were based on women who actively sought and received treatment, expectedly underestimating true disease incidence. CONCLUSIONS: Incidence rates of PPD and depression diagnoses increased over time, especially for PPD among primiparous and older mothers. These findings could suggest either increased vulnerability or increased awareness and detection over time in these groups. Fluctuating trends overserved from prescriptions could likely be driven by external factors and not a reflection of disease trends.

Epidemiologic Trends in Maxillofacial Trauma Surgery in Germany-Insights from the National DRG Database 2005-2022.

Background: Maxillofacial trauma (MFT) caused by falls, interpersonal violence or traffic accidents leading to fractures of different facial regions, including the midface and the mandible, are common clinical conditions requiring open reduction and internal fixation. The aim of this study was to analyze the incidence and time trends in MFT-associated surgeries regarding different facial regions in the German healthcare system over time. Materials and methods: Nationwide data regarding the national diagnosis-related group (DRG) inpatient billing system was received from the German Federal Statistical Office for the years 2005-2022. We estimated the age-gender standardized incidence of MFT-associated procedures classified by the Operation and Procedure Classification System (OPS) and evaluated age- and gender-adjusted time trends using Poisson regression analysis. Results: The total standardized incidence rate of MFT-associated procedures in the observational period 2005-2022 was 25.1 (♀13.3; ♂37.5) per 100,000 person-years within a slight significant annual decrease of 0.5%. A significant increase in the incidence of MFT-related procedures within the observational period was found in older adults from 60 to 79 years (+55.1%; ♀+54.8%; ♂+56.3%) and elderly patients over 80 years (+66.7%; ♀+59.1%; ♂+85.1%). Other significant trends are decreases in MFT-related procedures performed in children from 0-14 years (-28.1%; ♀-30.3%; ♂-27.3%) and young adults between 15 and 35 years (-20.4%; ♀-7.3%; ♂-22.5%). Conclusions: MFT-associated surgery is a persisting challenge in the German healthcare system. There is an ongoing transition in MFT-associated surgeries from younger to older patients beyond the scope of demographic change, highlighting the increasing importance of interdisciplinary treatment of patients with pre-existing conditions in maxillofacial surgery. Implementation of injury prevention measures might be beneficial in this population.

Characteristics of children with a psychiatric disorder in 1999, 2004 and 2017: an analysis of the national child mental health surveys of England.

BACKGROUND: While research has described the profile of children with poor mental health, little is known about whether this profile and their needs have changed over time. Our aim was to investigate whether levels of difficulties and functional impact faced by children with a psychiatric disorder have changed over time, and whether sociodemographic and family correlates have changed. METHODS: Samples were three national probability surveys undertaken in England in 1999, 2004 and 2017 including children aged 5-15 years. Psychiatric disorders were assessed using the Development and Well-Being Assessment (DAWBA), a standardised multi-informant diagnostic tool based on the tenth International Classification of Diseases (ICD-10). The impact and difficulties of having a disorder (emotional, behavioural or hyperkinetic) were compared over time using total difficulty and impact scores from the Strengths and Difficulties Questionnaire (SDQ). Analyses explored the impact of having any disorder, as well as for each disorder separately. Regression analyses compared associations between disorders and sociodemographic factors over time. RESULTS: Parent- and adolescent-reported total SDQ difficulty and impact scores increased between 1999 and 2017 for children and adolescents with disorders. No differences were noted when using teacher ratings. No differences in total SDQ difficulty score were found for children without a disorder. Comparison of sociodemographic correlates across the surveys over time revealed that ethnic minority status, living in rented accommodation and being in the lowest income quintile had a weaker association with disorder in 2017 compared to 1999. CONCLUSIONS: Our study reveals a concerning trend; children with a disorder in 2017 experienced more severe difficulties and greater impact on functioning at school, home and in their daily lives, compared to children with a disorder in earlier decades. Research is needed to identify and understand factors that may explain the changing nature and level of need among children with a disorder.

Cadmium Maximum Levels and Residue Situation in the German Wheat and Rye Harvest from 1975 to 2021.

For a better understanding of cadmium (Cd) accumulation over long time periods in cereals, Cd levels of the German wheat and rye harvest from 1975 to 2021 were analyzed. Overall, wheat had higher grain Cd concentrations than rye. Comparing mean values from different time periods showed that Cd levels in winter rye have stabilized, while Cd concentrations in winter wheat have decreased. Furthermore, Cd concentrations in almost all samples were below the newly introduced European Commission limits specifying the maximum permissible contaminant levels in foodstuffs (Cd in grains: rye 50 µg/kg FW; wheat 100 µg/kg FW). However, it is important to note that Cd is still ubiquitous in the German wheat and rye harvest. Although there has been a significant reduction in emissions and imissions for around 30 years, the extraordinarily long biological half-life and carcinogenicity of Cd still make it a relevant substance to food safety and human health.

Time trends in Alzheimer's disease mortality attributable to metabolic risks and smoking in China from 1990 to 2019: an age-period-cohort analysis.

Background: With the increase in the aging population worldwide, Alzheimer's disease has become a rapidly increasing public health concern. In the Global Burden of Disease Study 2019, there are three risk factors judged to have evidence for a causal link to Alzheimer's disease and other dementias: smoking, high body-mass index (HBMI), and high fasting plasma glucose (HFPG). Objective: This study aimed to analyze trends in AD mortality and the relevant burden across China from 1990 to 2019, as well as their correlation with age, period, and birth cohort. Methods: The data were extracted from the GBD 2019. Trends in AD mortality attributable to metabolic risks (HFPG and HBMI) and smoking were analyzed using Joinpoint regression. The age-period-cohort (APC) model was used to evaluate cohort and period effects. Results: From 1990 to 2019, the overall age-standardized mortality rate of AD increased, especially in women. There was an increase in AD mortality due to smoking in the net drift, and it was more significant in women (0.46, 95%CI = [0.09, 0.82]) than men (-0.03, 95%CI = [-0.11, 0.05]). For the cause of HFPG, the net drift values for men and women were 0.82% and 0.43%. For HBMI, the values were 3.14% and 2.76%, respectively, reflecting substantial increases in AD mortality. Conclusion: Time trends in AD mortality caused by metabolic risks and smoking in China from 1990 to 2019 have consistently increased. Therefore, it is necessary to prevent excessive weight gain and obesity during the later stages of life, especially for females.

Do Religiosity and Spirituality Differ in Their Relationship with Crystallized Intelligence? Evidence from the General Social Survey.

Negative associations of religiosity and intelligence are well established in psychological research. However, past studies have shown a substantial heterogeneity in reported effect strengths. Causes that may be able to explain the identified inconsistencies pertain to differing religiosity measurement modalities, participant ages, or possibly cohort effects due to changing societal values in terms of being religious. Moreover, little is known about intelligence associations with the religiosity-related yet distinct construct of spirituality. Here, we provide evidence for religiosity and crystallized intelligence, as well as spirituality and crystallized intelligence associations, in 14 cohorts from 1988 to 2022 (N = 35,093) in the General Social Survey data by means of primary data analyses and meta-analytical approaches. As expected, religiosity was non-trivially negatively associated (r = -0.13, p < .001), but spirituality showed no meaningful association with crystallized intelligence (r = 0.03, p < .001). Our results broadly generalized across age groups, cohorts, and analytical approaches, thus suggesting that religiosity and intelligence may possibly be functionally equivalent to a certain extent whilst spirituality represents a distinct construct that is not functionally equivalent.

Impact of the COVID-19 and War Migration on HIV/AIDS Epidemiology in Poland.

Objectives: This study analyzed trends in HIV/AIDS in Poland over the time period of 2009-2021 and the potential impact of COVID-19 and the migration of war refugees from Ukraine. Methods: Long-term trends were assessed by joinpoint regression using data from Polish HIV/AIDS registries. The HIV/AIDS burden was also compared before and during the pandemic and refugee migration. Results: In 2009-2021, the upward tendency in the rate of new HIV infections until 2017 and decrease after 2017 was accompanied by a downward trend in new HIV/AIDS diagnoses and mortality. From the pandemic's beginning until March 2022, rates of new HIV/AIDS diagnoses dramatically decreased to later increase to pre-pandemic levels, which partially coincided with the wave of migration of refugees from Ukraine. Conclusions: Long-term analysis of HIV/AIDS in Poland showed a downward trend in new HIV/AIDS diagnoses and related mortality in 2009-2021. While the pandemic has reduced the number of detected HIV/AIDS cases, a subsequent increase in new HIV diagnoses in 2022 may be related to lifting the COVID-19 restrictions and war refugees' migration. These observations have implications for the WHO European Region, seeking to end AIDS as a public health problem by 2030.

Sex ratio at birth across 100 years in Sweden and risk of cardiovascular disease and all-cause mortality - a national register study.

The human sex ratio at birth (SRB) undergoes temporary changes around a mean proportion of 0.51 male births. SRB has been well studied for historical, geographical, and secular trends, but until now not linked to health outcomes in the total population, e.g. for cardiovascular disease (CVD) or mortality during follow-up of birth cohorts. We used linkage analysis based on national registers in Sweden that cover all births from 1900 to 2016. SRB at birth was calculated by every 10-year birth cohort in all survivors living in 1997 for a follow-up analysis of risk of CVD and mortality with data from national registers. When the highest quartile of SRB was used as reference, a slightly increased risk of fatal CVD (HR 1.03 (95% confidence intervals, CI): 1.02-1.04), non-fatal CVD (HR 1.01; 95%CI: 1.01-1.02) and mortality (HR 1.02; 95%CI, 1.01-1.03) was found after full adjustments in men belonging to the lowest SRB quartile. A similar pattern was also found for fatal CHD in women. in the lowest SBR quartile compared to the highest, HR 1.03 (95%CI: 1.02-1.05). In conclusion, in birth cohorts with a relatively lower than expected number of males born, long-term adverse health effects were observed with slightly increased cardiovascular risk and total mortality at the population level. This could indicate that men belonging to so-called "culled cohorts" in a developed country during the 20th century are characterized by a slightly increased risk that could reflect negative early life influences and environmental exposures in pregnant women resulting in selective loss of male embryos or fetuses. In a public health perspective SRB could be of some importance to monitor as an aspect of birth statistics linked to relatively minor population health effects.

Potential asthma risk factors do not account for global asthma symptom prevalence patterns and time trends in children and adolescents.

Background: The International Study of Asthma and Allergies in Childhood (ISAAC) and the Global Asthma Network (GAN) conducted a series of global asthma prevalence surveys, between 1990 and 2020, in adolescents aged 13-14 and children aged 6-7 years. We used them to assess whether potential asthma risk factors explain global asthma symptom prevalence trends over this period. Method: We fitted mixed-effects linear regression models to estimate associations between centre-level risk factor prevalence and both the mid-point asthma symptom prevalence and the change per decade. We also estimated the 2019 asthma symptom prevalence across all included centres. Results: For adolescents, across 50 centres in 26 countries there was weak evidence that decreasing asthma prevalence over time was associated with regular fast-food consumption and frequent television viewing. However, frequent television viewing, along with heavy truck traffic, were associated with higher prevalence of asthma symptoms at the study mid-point. For children, across 41 centres in 21 countries, no risk factors were associated with time trends in asthma symptom prevalence, but truck traffic and paracetamol in the first year of life were associated with higher mid-point prevalence.We estimated the 2019 asthma symptom prevalence, across a total of 124 centres, to be 12.8% (11.4%, 14.2%) with little evidence of a difference by age. Low-income countries had lower prevalence (children 5.2% [2.5%, 7.8%], adolescents 5.3% [2.8%, 7.8%]), than lower-middle-, upper-middle- and high-income countries (all approximately 14-15%). Including risk factors in the models did not change the estimates. Conclusion: Potential asthma risk factors do not seem to explain the global prevalence patterns or time trends. Country income accounts for some of the differences, but the unexplained variation is very high.

Trends in socioeconomic inequalities in life expectancy and lifespan variation in Chile.

Background: Socioeconomic disparities in life expectancy are well-documented in various contexts, including Chile. However, there is a lack of research examining trends in life expectancy inequalities and lifespan variation over time. Addressing these gaps can provide crucial insights into the dynamics of health inequalities. Methods: This study utilizes data from census records, population surveys, and death certificates to compare the life expectancy and the lifespan variation at age 26 of individuals according to their rank in the distribution of years of education within their own birth cohort. The analysis spans three periods (1991, 2002, and 2017) and focuses on two educational groups: individuals in the first (lowest) quintile and tenth (highest) decile of educational attainment. Changes in life expectancy are disaggregated by major causes of death to elucidate their contributions to overall trends. Results: Consistent with existing literature, our findings confirm that individuals with lower education levels experience lower life expectancy and higher lifespan variation compared to their more educated counterparts. Notably, by 2017, life expectancy for individuals in the lowest quintile of education has caught up with that of the top decile in 1991, albeit with contrasting trends between genders. Among women, the gap has reduced, while it has increased for males. Moreover, lifespan variation decreased (increased) over time for individuals in the tenth decile (first quintile). The leading causes of death that explain the increase in life expectancy in women and men in the tenth decile as well as women in the first quintile are cardiovascular, cancer, respiratory and digestive diseases. In the case of males in the first quintile, few gains have been made in life expectancy resulting from cancer and a negative contribution is associated with digestive conditions. Conclusions: This study underscores persistent socioeconomic disparities in life expectancy in Chile, emphasizing the importance of ongoing monitoring of health inequalities across different demographic segments. The gender-specific and educational gradient trends highlight areas for targeted interventions aimed at reducing health disparities and improving overall population health outcomes. Further research is warranted to delve into specific causes of death driving life expectancy differentials and to inform evidence-based policy interventions.

Temporal Trends in Urinary Diversion among Patients Undergoing Radical Cystectomy Between 1986 and 2022: Experience at the University Medical Center Mainz with 2224 Cases.

BACKGROUND: Analysis of temporal trends of urinary diversion (UD) and identification of predictive factors for continent urinary diversion (CUD) in patients with bladder cancer (BC) is scarce and data on large cohorts are missing. We aimed to describe longitudinal temporal trends and predictive factors for UD among patients with BC receiving radical cystectomy (RC). PATIENTS AND METHODS: We retrospectively analysed institutional data collected from patients undergoing RC from 1986 to 2022 to describe changes in patients' characteristics and UD. Primary end points were patients' characteristics associated with type of UD. Logistic regression analysis was used to determine predictive factors for CUD. RESULTS: In total, 2224 patients (77.16% male, 22.84% female) with a mean age of 66 years [standard deviation (SD), 10.64 years] were included. We observed an increase in mean age from 59.86 (10.8) years (1986-1990) to 69.85 (9.99) years (2016-2022) (p < 0.001). The proportion of CUD gradually declined from 43.72% (94/215; 1986-1990) to 18.38% (86/468; 2016-2022). Patients who were male [odds ratio (OR): 1.92, 95% confidence interval (CI): 1.43-2.57, p < 0.001), younger (OR: 0.88, 95% CI: 0.87-0.89, p < 0.001) and had no hydronephrosis prior to RC (OR: 2.2, 95% CI: 1.66-2.92, p < 0.001) were more likely to receive CUD. CONCLUSIONS: We report the largest European single-center cohort of UD after RC, demonstrating a significant shift from CUD to IUD, accompanied by an increasing age. Finally, our data mirrors the development and extensive experience with the Mainz Pouch-I in the 1980's and 1990's together with other colon pouches.

Time trends of the association of body mass index with mortality in 3.5 million young Swedish adults.

PURPOSE: We investigated time trends of the obesity-mortality association, accounting for age, sex, and cause-specific deaths. METHODS: We analysed pooled nationwide data in Sweden for 3,472,310 individuals aged 17-39 years at baseline in 1963-2016. Cox regression and flexible parametric survival models investigated BMI-mortality associations in sub-groups of sex and baseline calendar years (men: <1975, 1975-1985, ≥1985 and women: <1985, 1985-1994, ≥1995). RESULTS: Comparing men with obesity vs. normal weight, all-cause and "other-cause" mortality associations decreased over periods; HR (95% CI) 1.92 (1.83-2.01) and 1.70 (1.58-1.82) for all-cause and 1.72 (1.58-1.87) and 1.40 (1.28-1.53) for "other-cause" mortality in <1975 and ≥1985, but increased for CVD mortality; HR 2.71 (2.51-2.94) and 3.91 (3.37-4.53). Higher age at death before 1975 coincided with more obesity-related deaths at higher ages. Furthermore, the all-cause mortality association for different ages in men showed no clear differences between periods (p-interaction=0.09), suggesting no calendar effect after accounting for attained age. Similar, but less pronounced, results were observed in women. Associations with cancer mortality showed no clear trends in men or in women. CONCLUSIONS: Accounting for differences in age and death causes between calendar periods when investigating BMI-mortality time trends may avoid misinterpreting the risks associated with obesity over time.

A decade of data and hundreds of analytes: Legacy and emerging chemicals in North American herring gull plasma.

Between 2010 and 2021, 199 herring gull serum samples were collected from Lake Michigan, Lake Huron, and Lake Erie, including two Areas of Concern: Saginaw Bay and the River Raisin. They were analyzed for 21 polybrominated diphenyl ether congeners, 10 non-PBDE flame retardants, 85 polychlorinated biphenyls, 17 legacy organochlorine pesticides, and 36 per- and polyfluoroalkyl substances. Σ36PFAS, Σ85PCB, Σ21PBDE, and Σ17Pesticide concentrations comprised 41-74%, 17-50%, 3-4%, and 5-9% of the total concentration, respectively. Median concentrations of the chemical groups ranged from 81.5 to 129 ng/g ww for PFAS, 26.3-158 ng/g ww for PCBs, 4.26-8.89 ng/g ww for PBDEs, and 8.08-23.0 ng/g ww for pesticides. The regional concentrations of all four classes of compounds are significantly decreasing when sites are combined with halving times of 11.3 ± 4.8, 8.2 ± 4.3, 5.9 ± 3.1, and 8.3 ± 4.2 years for the Penta-BDE mixture, ΣDDTs, Σ85PCBs and Σ36PFAS, respectively. These results suggest that, while PFAS has emerged as the dominant group of chemicals in the plasma, legacy pollutants continue to represent a threat to herring gulls and wildlife in the Great Lakes basin. PCBs were the largest contributors to the chemical load in plasma of birds whose colonies are located near the River Raisin, and continue to pose a threat to herring gulls within the two Areas of Concern.

Time trends in proximal humeral fractures from 1944 to 2020 - A cohort study in Malmö, Sweden.

BACKGROUND: Most studies infer increasing incidence of proximal humeral fractures (PHF) from the 1950´s until the 1990´s. Recent time trends are less clear. OBJECTIVES: Our primary objective was to identify time trends in the age- and sex-adjusted adult incidence of PHF in Malmö, Sweden, from year 1944 until 2020. Our secondary objectives were to describe the variation in incidence according to age, the monthly distribution, and to compare data from the two most recent decades with earlier. STUDY DESIGN AND METHODS: Malmö has one emergency hospital where acute fractures are treated. We identified PHF in adult patients (≥ 18 years) by reviewing relevant radiology examinations during 17 sample years from year 1944 to 2020. We used jointpoint analyses to estimate time trends. RESULTS: We identified 3 031 PHF during the study period (3 231 161 person years), 73% were sustained by women with mean age of 69 years (mean age in men 59). Joinpoint analyses indicated an increase in the age- and sex-adjusted incidence of PHF from year 1944 (52 per 100 000 person years) until 1977 (120 per 100 000) and thereafter a decrease until 2020 (85 per 100 000). A seasonal variation with more fractures during winter months, was apparent in earlier but not recent decades. CONCLUSIONS: The age- and sex-adjusted incidence of PHF increased in Malmö, Sweden, from the 1940´s until year 1977 and thereafter decreased until 2020. More fractures were seen during winter months in earlier but not recent decades.

Epidemiology of acute lymphoblastic leukaemia in Sardinia, Italy: Age, sex, and environmental correlates.

Using a database of 1974-2003 incident cases of haematological malignancies, we explored the time trend, geographic spread and socio-economic and environmental correlates of ALL incidence in Sardinia, Italy, by sex and age. The age- and sex-standardized (World population) ALL incidence rate was 2.0 per 100,000 (95% CI 1.8 - 2.1) and showed variable trend patterns by sex and age. In the total population, ALL incidence showed an annual per cent change of -1.4% (95% CI -0.59 - -3.34) over the study period, with a knot separating a downward slope in 1974-1996 from an increase in 1996-2003. ALL incidence replicated such pattern in women but not men, whose incidence did not substantially vary over the study period (APC = -2.57%, 95% CI -5.45 - 0.26). Among women, the spatial analysis suggested a clustering of ALL in the southwestern part of the region, whilst only a commune had a high posterior probability of a high ALL incidence among men. Three unrelated communes showed a high posterior probability of ALL at age ≤ 24; only the most populated urban centre showed excess cases at age ≥ 25 years. There was no correlation between the geographic spread of ALL at ages ≤ 24 and ≥ 25 years (p = 0.082). Urban residence was a risk factor for the younger age group. Residences near industrial settlements and in the most populated urban centre were risk factors for subjects aged ≥ 25 years. Our findings suggest age-related differences in ALL aetiology.

Time trends and regional variations in prices of anticancer medicines in China.

Introduction: High prices, as a main factor, contributed to the lack of adequate access to essential anticancer medicines, especially for patients in developing countries. The Chinese Government has introduced a series of policies to control the prices of medicines during the last decade, but the effect on anticancer medicine is not yet clear. Methods: To evaluate the time trends and regional variation in the price of essential anticancer medicines in China, we used the procurement data of anticancer medicines from 2015 to 2022. We selected 29 anticancer medicines from the 2018 Chinese National Essential Medicines List. To measure the cost of a medicine, we used defined daily dose cost -the cost per defined daily doses. At national level, we focused on the price changes over time and compared the price between medicine categories. At provincial level, we assessed price variation among provinces over time. Results: For prices at the national level, all 6 targeted medicines exhibited a continuous decrease trend in price. Out of 23 non-targeted medicines, 4 (17·39%) experienced continuous increases in prices, and 9 (39·13%) showed price decreases from 2015 to 2019 and then an upward trend during 2019-2022; Of the remaining non-targeted medicines, 7 (30·43%) had continuous price decreases and 3 (13.04%) had price increases followed by decreases. For prices at the provincial level, provincial price variation became smaller for almost all targeted medicines, except rituximab; for 11 out of 23 non-targeted medicines, provincial price variations became larger. During the study period, the proportion of price-increased medicines in each province was geographically correlated, and no significant relationship between prices and GDP per capita was observed for both targeted and non-targeted anticancer medicines. Conclusion: The prices and regional disparity of most targeted anticancer medicines were decreasing, while for nearly half of the non-targeted anticancer medicines, the prices were increasing and the regional disparity became wider, which may lead to compromised access to these essential anticancer medicines and raise inequity health outcome among regions.

Unveiling sex-based geographical disparities in myelodysplastic syndrome mortality trends in Spain (1999-2022).

AIM: To comprehensively analyze trends in myelodysplastic neoplasm (MDS) mortality across Spain (1999-2022), examining sex and regional differences. METHODS: We analyzed nationwide death records and population data, calculating age-standardized mortality rates (ASMRs) and standardized mortality ratios (SMRs) stratified by sex and Autonomous Community (AC). Joinpoint regression identified significant shifts in trends. RESULTS: Across Spain, MDS mortality risk varied among men, with rates ranging from 1.08 to 4.38 per 100,000 across regions, while women's rates ranged from 1.23 to 2.02. Five regions had higher risks than the national average, while six had lower risks. Joinpoint analysis revealed three periods nationally: a decline until 2008, and an increase until 2017, followed by a significant decrease. Despite the overall stable national trend (-0.5% annual change), significant regional variations emerged. Andalusia stood out with a worrying increase in MDS mortality, while Aragon and Murcia demonstrated promising declines. Extremadura displayed a unique trajectory with an initial rise followed by stabilization, while Galicia exhibited a contrasting trend with an initial decline and subsequent increase. Notably, men consistently faced a higher risk of MDS mortality compared to women, with significant disparities across regions. Extremadura, in particular, showed a marked difference in risk between genders. CONCLUSION: MDS mortality trends in Spain are complex, and influenced by gender, region, and time. Further research is needed to understand regional disparities, recent national decline, and higher risk in specific demographics. Tailored interventions based on local factors and targeted research are crucial to address these complexities and improve patient outcomes.