Cohort Data Research Articles

Non-health-targeted promotions and step counts of smartphone-based mall walking program users

Abstract Background The COVID-19 pandemic changed lifestyles and raised concerns regarding physical inactivity among adults. Mobile health interventions for physical activity may be a potential solution. However, the effects may diminish over time. This study investigated whether incorporating non-health-targeted promotions into an existing mobile health-walking program could stimulate users to walk. Methods We used nationwide cohort data of smartphone users participating in a shopping mall walking program in Japan. We focused on existing users registered in the program until October 31, 2022. A Japanese anime tie-in promotion was conducted by the shopping mall company from December 3 to 25, 2022, offering additional rewards alongside the regular program. We collected step count records of existing users 1 month before and after (November 1 to December 2, 2022, and December 26, 2022 to January 31, 2023, respectively), and during the promotion period. Propensity score matching was applied to ensure balance in the baseline characteristics of existing users in terms of gender, age, and pre-promotion program participation frequency. Next, we analyzed the association between participation in the promotion program and the average daily step counts during and after the promotional period using mixed effects models for repeated measures, while adjusting for the same covariates. Results Among the 18,156 users included in the study, 13,386 (73.7%) were women, with a mean (SD) age of 45.2 (12.7) years, and a mean (SD) pre-promotion program participation frequency of 9.7 (9.6) per month. During the promotion period, the participants walked 87 (95% CI: 50-125) more steps per day than non-participants, after adjusting for covariates. No clear association was observed 1 month post-promotion. Conclusions These findings indicate that non-health-targeted promotions may be short-term motivators for existing app users to walk. Ongoing monitoring is necessary to assess the long-term impact. Key messages • Mobile health intervention effects may diminish over time. • A non-health-related promotion could stimulate existing mall walking program app users to increase their daily step count temporarily.

The effects of hypothetical psychological interventions on alcohol use in European young adults

Abstract Background Low psychosocial well-being (PWB) and high emotion-driven impulsiveness (EDI) are associated with alcohol. Yet, it is unclear whether a hypothetical intervention targeting one or the other in adolescence might be more effective in reducing alcohol consumption (AC) in young adulthood. Therefore, we aimed to compare the separate causal effects of PWB and EDI in adolescence on AC in young adulthood. Methods We included 505 European young adults from the IDEFICS/I.Family cohort (mean age: 20.2 years; age range: 18.2-23.5 years) who did not drink alcohol at study entry. AC was operationalized as the amount of weekly consumed alcoholic beverages (mean: 4.2 drinks per week; range: 0.3-70 drinks per week). EDI was assessed using the negative urgency subscale from the UPPS-P Impulsive Behaviour Scale. PWB was assessed using the KINDLR Health-Related Quality of Life Questionnaire. Following the principles of target trial emulation, we estimated, separately, the average causal effects of PWB and EDI on AC accounting for relevant confounders and applying a semi-parametric doubly robust method (targeted maximum likelihood estimation). We stratified the results by sex and parental education. Results If all adolescents, hypothetically, had high levels of PWB, compared to low levels, we estimated a decrease in the average amount of alcoholic beverages in young adulthood by 0.1 drinks per week [95%-confidence interval: -2.3; 2.1]. Furthermore, if all adolescents had low levels of EDI, compared to high levels, we estimated an increase in alcoholic beverages in young adulthood by 1.5 drinks per week [0.1; 2.9]. Different effects for sex and parental education groups were found. Conclusions Hypothetical interventions targeting PWB in adolescents were not found to have effects on reducing AC in young adulthood. Interventions targeting EDI, however, would lead to an increase in AC. This may be due to unmeasured confounding and the missing distinction between drinking motives. Key messages • We demonstrate that causal inference methods, compared to traditional ones, improve the robustness of estimated effect measures and address important sources of bias in European cohort data. • To inform public health interventions on reducing alcohol consumption, future research should investigate different drinking motives, e.g. alleviating negative emotions or enhancing positive emotions.

Inequalities in preterm birth by deprivation and ethnicity: A national cohort study in England

Abstract Background Preterm birth has decreased in the UK; however, the extent of inequalities remains unclear. This study aimed to quantify socioeconomic and ethnic inequalities in preterm birth rates using routinely collected maternity data in England. Methods Retrospective analysis of cohort data from the NHS England Hospital Episode Statistics (HES). All women aged 13-55 with a singleton livebirth (April 2018 to March 2021) at 24-42 weeks were included. Multivariate Poisson regression was used to estimate the rate of preterm birth (livebirth between 24 + 0 and 36 + 6 weeks’) for each ethnic and deprivation postcode group, these were compared to white women from the least deprived 20% of areas. We iteratively developed the model, adjusting for covariates associated with preterm birth. A post-hoc calculation identified the rate of preterm birth for each ethnic group at each level of deprivation. Results We identified 1,111,045 livebirths between April 2018 and March 2021. The rate of preterm birth increased with socioeconomic deprivation and was highest at 7.1% per 100 livebirths (95%CI:7.00-7.20) in women living in the 20% most deprived areas, compared to 5.6% (95%CI:5.50-5.74) in women in the 20% least deprived areas. White women had the lowest preterm birth rate at 6.5% (95%CI:6.47-6.58) and South Asian women had the highest rate at 6.9% (95%CI:6.76-7.04) (Table 2). The rate of preterm birth increased according to increased area-level deprivation across all ethnic groups. In areas of high deprivation, the preterm birth rate was similar across ethnic groups. Whereas in less deprived areas, there were marked inequalities between ethnic groups. Conclusions Inequalities in preterm birth remain, despite overall decreases in preterm birth. We found area deprivation and individual ethnicity interact to increase the risk of preterm birth in marginalized communities. Interventions need to holistically consider the structural and socioenvironmental determinants of preterm birth. Key messages • Area deprivation and ethnicity remain key drivers of inequalities in preterm birth, despite overall decreases in preterm birth. • To reduce inequalities tailored prevention strategies are needed to address socioenvironmental and structural determinants of preterm birth in high deprivation areas and minoritized ethnicity groups.

Determinants of Length of Stay for Medical Inpatients Using Survival Analysis

With the increase in insured patients and an aging population, managing the length of stay (LOS) for inpatients has become crucial for controlling medical costs. Analyzing the factors influencing LOS is necessary for effective management. Previous studies often used multiple or logistic regression analyses, which have limitations such as unmet assumptions and the inability to handle time-dependent variables. To address these issues, this study applied survival analysis to examine the factors affecting LOS using the National Health Insurance Service (NHIS) sample cohort data from 2016 to 2019, covering over 4 million records. We used Kaplan–Meier survival estimation to assess LOS probabilities based on sociodemographic, patient, health checkup, and institutional characteristics. Additionally, the Cox proportional hazards model controlled for confounding factors, providing more robust validation. Key findings include the influence of age, gender, type of insurance, and hospital type on LOS. For instance, older patients and medical aid recipients had longer LOS, while general hospitals showed shorter stays. This study is the first in Korea to use survival analysis with a large cohort database to identify LOS determinants. The results provide valuable insights for shaping healthcare policies aimed at optimizing inpatient care and managing hospital resources more efficiently.

High-resolution subtyping of fibroblasts in gastric cancer reveals diversity among fibroblast subsets and an association between the MFAP5-fibroblast subset and immunotherapy.

Gastric cancer (GC) remains a global health threat due to frequent treatment failures caused by primary or acquired resistance. Although cancer-associated fibroblasts (CAFs) have been implicated in this process, it is still unclear which specific subtype(s) of CAFs hinder T-cell infiltration and promote resistance to immunotherapy. We analyzed the GC fibroblast atlas in detail by combining 63,955 single cells from 14 scRNA-seq datasets. We also performed RNA-seq data in a local GC cohort and examined 13 bulk RNA-seq datasets to understand the biological and clinical roles of different CAF subsets. Additionally, we conducted in vitro experiments to study the role of specific proteins in GC development. We identified a total of 17 fibroblast subsets in gastric cancer, nine of which did not fit into the existing CAFs classification. These subsets exhibited significant heterogeneity in distribution and biological characteristics (metabolism, cell-cell interactions, differentiation state), as well as clinical functions such as prognosis and response to immunotherapy. In particular, cluster 6 stood out for its high expression of MFAP5, CFD, and PI16; it was found to be negatively associated with both overall survival and response to immunotherapy in GC. This association was linked to an immunosuppressive microenvironment characterized by an increase in M2 macrophages but higher levels of T cell dysfunction and exclusion-a feature shared by tumors expressing MFAP5. Furthermore, the addition of human recombinant MFAP5 promoted proliferation and migration of HGC-27 cells by inducing the MFAP5/NOTCH1/HEY1 signaling pathway. We introduce a high-resolution GC fibroblast atlas. The 17 identified fibroblast clusters provide valuable opportunities for gaining deeper biological insights into the relationship between fibroblasts and GC development. Particularly, cluster 6 and its specific marker MFAP5 could serve as prognostic factors in GC and form a foundation for personalized therapeutic combinations to address primary resistance to ICIs.

Digital Phenotyping of Mental and Physical Conditions: Remote Monitoring of Patients Through RADAR-Base Platform.

The use of digital biomarkers through remote patient monitoring offers valuable and timely insights into a patient's condition, including aspects such as disease progression and treatment response. This serves as a complementary resource to traditional health care settings leveraging mobile technology to improve scale and lower latency, cost, and burden. Smartphones with embedded and connected sensors have immense potential for improving health care through various apps and mobile health (mHealth) platforms. This capability could enable the development of reliable digital biomarkers from long-term longitudinal data collected remotely from patients. We built an open-source platform, RADAR-base, to support large-scale data collection in remote monitoring studies. RADAR-base is a modern remote data collection platform built around Confluent's Apache Kafka to support scalability, extensibility, security, privacy, and quality of data. It provides support for study design and setup and active (eg, patient-reported outcome measures) and passive (eg, phone sensors, wearable devices, and Internet of Things) remote data collection capabilities with feature generation (eg, behavioral, environmental, and physiological markers). The back end enables secure data transmission and scalable solutions for data storage, management, and data access. The platform has been used to successfully collect longitudinal data for various cohorts in a number of disease areas including multiple sclerosis, depression, epilepsy, attention-deficit/hyperactivity disorder, Alzheimer disease, autism, and lung diseases. Digital biomarkers developed through collected data are providing useful insights into different diseases. RADAR-base offers a contemporary, open-source solution driven by the community for remotely monitoring, collecting data, and digitally characterizing both physical and mental health conditions. Clinicians have the ability to enhance their insight through the use of digital biomarkers, enabling improved prevention, personalization, and early intervention in the context of disease management.

Genetic Prediction Modeling in Large Cohort Studies via Boosting Targeted Loss Functions.

Polygenic risk scores (PRS) aim to predict a trait from genetic information, relying on common genetic variants with low to medium effect sizes. As genotype data are high-dimensional in nature, it is crucial to develop methods that can be applied to large-scale data (large and large ). Many PRS tools aggregate univariate summary statistics from genome-wide association studies into a single score. Recent advancements allow simultaneous modeling of variant effects from individual-level genotype data. In this context, we introduced snpboost, an algorithm that applies statistical boosting on individual-level genotype data to estimate PRS via multivariable regression models. By processing variants iteratively in batches, snpboost can deal with large-scale cohort data. Having solved the technical obstacles due to data dimensionality, the methodological scope can now be broadened-focusing on key objectives for the clinical application of PRS. Similar to most methods in this context, snpboost has, so far, been restricted to quantitative and binary traits. Now, we incorporate more advanced alternatives-targeted to the particular aim and outcome. Adapting the loss function extends the snpboost framework to further data situations such as time-to-event and count data. Furthermore, alternative loss functions for continuous outcomes allow us to focus not only on the mean of the conditional distribution but also on other aspects that may be more helpful in the risk stratification of individual patients and can quantify prediction uncertainty, for example, median or quantile regression. This work enhances PRS fitting across multiple model classes previously unfeasible for this data type.

Bringing the group back in: Social class and resistance in adolescent smoking.

Absolute prevalence of tobacco smoking has fallen in recent decades but inequalities by socioeconomic position (SEP) persist. Adolescence is a critical period for smoking initiation and habits formed during this period likely continue into adulthood. Explanations for inequalities in adolescent smoking have tended to focus on individualistic theories based on differentials in knowledge and psychology. These have been criticised for their blindness to processes of social stratification and social context that influence smoking behaviours. Based on previous social theories, we put forward, and test empirically, two potential structural explanations for inequalities in smoking, using nationally representative longitudinal cohort data on 6039 Irish young people aged 9-18years. Descriptive analyses confirmed the adverse SEP gradient in smoking prevalence as well as SEP gradients in variables representing individual-level characteristics and structural-level explanations. Despite lower self-esteem being associated with a higher likelihood of smoking, there was no significant indirect pathway between SEP and smoking via self-esteem. Path analyses found that differentials in exposure to parental smoking and levels of oppositional values mediate the relationship between SEP and smoking. Our results favour structural and group-based explanations for inequalities, that is, the 'smoking exposure' and 'social resistance' models, over explanations based on individual psychology.

Social inequalities in child mental health trajectories: a longitudinal study using birth cohort data 12 countries

BackgroundSocial inequalities in child mental health are an important public health concern. Whilst previous studies have examined inequalities at a single time point, very few have used repeated measures outcome data to describe how these inequalities emerge. Our aims were to describe social inequalities in child internalising and externalising problems across multiple countries and to explore how these inequalities change as children age.MethodsWe used longitudinal data from eight birth cohorts containing participants from twelve countries (Australia, Belgium, Denmark, France, Germany, Greece, Italy, Netherlands, Poland, Norway, Spain and the United Kingdom). The number of included children in each cohort ranged from N = 584 (Greece) to N = 73,042 (Norway), with a total sample of N = 149,604. Child socio‐economic circumstances (SEC) were measured using self‐reported maternal education at birth. Child mental health outcomes were internalising and externalising problems measured using either the Strengths and Difficulties Questionnaire or the Child Behavior Checklist. The number of data collection waves in each cohort ranged from two to seven, with the mean child age ranging from two to eighteen years old. We modelled the slope index of inequality (SII) using sex‐stratified multi‐level models.ResultsFor almost all cohorts, at the earliest age of measurement children born into more deprived SECs had higher internalising and externalising scores than children born to less deprived SECs. For example, in Norway at age 2 years, boys born to mothers of lower education had an estimated 0.3 (95% CI 0.3, 0.4) standard deviation higher levels of internalising problems (SII) compared to children born to mothers with high education. The exceptions were for boys in Australia (age 2) and both sexes in Greece (age 6), where we observed minimal social inequalities. In UK, Denmark and Netherlands inequalities decreased as children aged, however for other countries (France, Norway, Australia and Crete) inequalities were heterogeneous depending on child sex and outcome. For all countries except France inequalities remained at the oldest point of measurement.ConclusionsSocial inequalities in internalising and externalising problems were evident across a range of EU countries, with inequalities emerging early and generally persisting throughout childhood.

Disease progression associated cytokines in COVID-19 patients with deteriorating and recovering health conditions.

Understanding the immune response to COVID-19 is challenging due to its high variability among individuals. To identify differentially expressed cytokines between the deteriorating and recovering phases, we analyzed the Electronic Health Records (EHR) and cytokine profile data in a COVID-19 cohort of 444 infected patients and 145 non-infected healthy individuals. We categorized each patient's progression into Deterioration Phase (DP) and Recovery Phase (RP) using longitudinal neutrophil, lymphocyte and lactate dehydrogenase levels. A random forest model was built using healthy and severe patients to compute the contribution of each cytokine toward disease progression using Shapley Additive Explanations (SHAP). SHAP values were used for supervised clustering to identify DP and RP-related samples and their associated cytokines. The identified clusters effectively discriminated DP and RP samples, suggesting that the cytokine profiles differed between deteriorating and recovering health conditions. Especially, CXCL10, GDF15, PTX3, and TNFSF10 were differentially expressed between the DP and RP samples, which are involved in the JAK-STAT, NF- B, and MAPK signaling pathways contributing to the inflammatory response. Collectively, we characterized the immune response in terms of disease progression of COVID-19 with deteriorating and recovering health conditions.

Shared Genetic Architecture and Causal Relationship between Serum 25-Hydroxyvitamin D and Bone Mineral Density.

Despite the well-established regulatory role of vitamin D in maintaining bone health, little is known about the shared genetics and causality of the association between serum 25-hydroxyvitamin D (25OHD) and bone mineral density (BMD). Leveraging individual-level data from the UK Biobank (UKB) cohort and summary-level data from the genome-wide association studies (GWASs) conducted on European individuals for serum 25OHD (N = 417,580) and estimated heel BMD (eBMD, N = 426,824), we systematically elucidated the shared genetic architecture underlying serum 25OHD and eBMD through a comprehensive genome-wide cross-trait design. Despite a lack of global genetic correlation (rg = -0.001, P = 0.95), a significant local signal was discovered at 5p11-5q11.9. Two-sample Mendelian randomization (MR) indicated no causal association in the overall population (β = 0.003, 95% CI = -0.04∼0.03, P = 0.93), while positive causal effects were observed in males (β = 0.005, 95% CI = 0.00∼0.01, P = 0.03) and the elderly (β = 0.009, 95% CI = 0.00∼0.02, P = 0.01) according to one-sample MR. A total of 49 pleiotropic SNPs, with 4 novel SNPs (rs1077151, rs79873740, rs12150353, and rs4760401), were identified, and a total of 95 gene-tissue pairs exhibited overlap, predominantly enriched in the nervous, digestive, exo-/endocrine and cardiovascular systems. Protein-protein interaction analysis identified RPS9 and RPL7A as hub genes. This study illuminates the potential health benefits of enhancing serum 25OHD levels to mitigate the risk of osteoporosis among males and the elderly. It also unveils a shared genetic basis between serum 25OHD and eBMD, offering valuable insights into the intricate biological pathways.

Identifying pathogenic variants in rare pediatric neurological diseases using exome sequencing.

Variant annotations are crucial for efficient identification of pathogenic variants. In this study, we retrospectively analyzed the utility of four annotation tools (allele frequency, ClinVar, SpliceAI, and Phenomatcher) in identifying 271 pathogenic single nucleotide and small insertion/deletion variants (SNVs/small indels). Although variant filtering based on allele frequency is essential for narrowing down on candidate variants, we found that 13 de novo pathogenic variants in autosomal dominant or X-linked dominant genes are registered in gnomADv4.0 or 54KJPN, with an allele frequency of less than 0.001%, suggesting that very rare variants in large cohort data can be pathogenic de novo variants. Notably, 38.4% candidate SNVs/small indels are registered in the ClinVar database as pathogenic or likely pathogenic, which highlights the significance of this database. SpliceAI can detect candidate variants affecting RNA splicing, leading to the identification of four variants located 11 to 50bp away from the exon-intron boundary. Prioritization of candidate genes by proband phenotype using the PhenoMatcher module revealed that approximately 95% of the candidate genes had a maximum PhenoMatch score ≥ 0.6, suggesting the utility of phenotype-based variant prioritization. Our results suggest that a combination of multiple annotation tools and appropriate evaluation can improve the diagnosis of rare diseases.

Clinical and dental predictors of preterm birth using machine learning methods: the MOHEPI study.

Preterm birth (PTB) is one of the most common and serious complications of pregnancy, leading to mortality and severe morbidities that can impact lifelong health. PTB could be associated with various maternal medical condition and dental status including periodontitis. The purpose of this study was to identify major predictors of PTB among clinical and dental variables using machine learning methods. Prospective cohort data were obtained from 60 women who delivered singleton births via cesarean section (30 PTB, 30 full-term birth [FTB]). Dependent variables were PTB and spontaneous PTB (SPTB). 15 independent variables (10 clinical and 5 dental factors) were selected for inclusion in the machine learning analysis. Random forest (RF) variable importance was used to identify the major predictors of PTB and SPTB. Shapley additive explanation (SHAP) values were calculated to analyze the directions of the associations between the predictors and PTB/SPTB. Major predictors of PTB identified by RF variable importance included pre-pregnancy body mass index (BMI), modified gingival index (MGI), preeclampsia, decayed missing filled teeth (DMFT) index, and maternal age as in top five rankings. SHAP values revealed positive correlations between PTB/SPTB and its major predictors such as premature rupture of the membranes, pre-pregnancy BMI, maternal age, and MGI. The positive correlations between these predictors and PTB emphasize the need for integrated medical and dental care during pregnancy. Future research should focus on validating these predictors in larger populations and exploring interventions to mitigate these risk factors.

Distinct genetic signals at the FGF21 locus complicate studies of FGF21's role in diet regulation using human cohort data

ObjectivesExperimental and genetic studies suggest that fibroblast growth factor 21 (FGF21) modulates macronutrient and alcohol preferences, but evidence of such regulation in humans remains scarce. To address this gap in translation, we aimed to map the relationships between plasma FGF21 levels, FGF21 genetic variation and habitual macronutrient intake in a large human population. MethodsWe fine-mapped and performed colocalization of the FGF21 genetic region in GWAS summary statistics of plasma FGF21 levels and macronutrient intake. UK Biobank data were used to investigate the associations between FGF21 genetic variants, plasma FGF21 protein levels, and macronutrient intake (including alcohol) assessed with repeated 24-hour recalls. One- and two-sample mendelian randomization were performed to estimate the effects of plasma FGF21 on macronutrient intake. ResultsWe show that the main macronutrient-associated variant rs838133 and the FGF21 cis-pQTL rs838131, both in the FGF21 gene, are distinct genetic signals. Effect directions also suggest that the influence of FGF21 variation on macronutrient intake appear more complex than by direct mediation through plasma FGF21. Only when considering this complexity at FGF21, is plasma FGF21 estimated to reduce alcohol and increase protein and fat intake using mendelian randomization. Importantly, plasma FGF21 levels also appear markedly elevated by primarily high alcohol and low protein intake. ConclusionsThese findings support the feedback diet-regulatory mechanism of FGF21 in humans, but highlights the need for mechanistic characterization of the complex FGF21 genetic region.

The association between integrating echocardiography use in the management of septic shock patients and outcomes in the intensive care unit: a systematic review and meta-analysis.

Septic shock in critically ill patients can increases morbidity and mortality. We aimed to study the effect on outcomes when integrating point of care (POC) echocardiography in the management of septic shock patients in the Intensive Care Unit (ICU) who are being treated according to the Surviving Sepsis Campaign (SSC) guidelines. An electronic search of MEDLINE through PubMed, clinical trials.gov and google scholar was conducted for the period from January 1990-January 2024 to identify studies of septic shock adult and pediatric patients in the ICU managed according to SSC guidelines with or without POC echocardiography. Three reviewers extracted data independent of each other. Cochrane collaboration tool was used for bias assessment. Random effect meta-analysis used to pool data. A total of 1701 articles identified. Seven studies included in the final report with a total of 3885 patients. POC echocardiography guided septic shock management was associated with lower in-hospital and 28-day mortality (sOR = 0.82 [95%CI: 0.71-0.95], p = 0.01), more frequent initiation of inotropic support (sOR = 2.42 [95%CI 1.92-3.03], p < 0.0001) and shorter time to achieve lactate clearance (SMD = - 0.87h [95%CI - 1.23h to - 0.51h], p < 0.0001). Summary estimates did not achieve significance for effect of POC echocardiography on 24-h fluid intake (SMD = - 2.11ml [95%CI - 5.93ml to 1.72ml], p = 0.28) on mechanical ventilation-free days (SMD = 0.03days [95%CI - 0.04 to 0.10], p = 0.94). Shock reversal time analysis was less meaningful due to the small number of studies reporting outcome. POC echocardiography guided management in septic shock patients in the ICU can lead to a decrease in mortality, increase in initiation of inotropic support, and a decrease in lactate clearance time. Larger cohort studies and data collection and analysis are needed for further understanding and optimizing standardization of protocols for POC echocardiography use in septic shock patients in the ICU.

From a solitary blood-derived biomarker to combined biomarkers of sarcopenia: Experiences from the Korean Frailty and Aging Cohort Study.

Sarcopenia is recognized as a complex and multifactorial disorder that includes nutritional deficiency, inactivity, proinflammatory status, hormonal changes, neurological degeneration, and metabolic disturbances. Its' pathogenesis is not fully understood. Therefore, identifying specific biomarkers of sarcopenia will help us understand its pathophysiology. The most frequently reported blood-derived biomarkers of sarcopenia are growth factors, neuromuscular junctions, endocrine systems, mitochondrial dysfunction, inflammation-mediated and redox processes, muscle protein turnover, blood metabolomics, and behavior-mediated biomarkers. Here, we address the implications of sarcopenia biomarkers based on our research experience with KFACS cohort data. It includes free testosterone, myostatin, fibroblast growth factor 21 (FGF-21), growth differentiation factor 15 (GDF-15), procollagen type III N-terminal peptide (P3NP), creatinine-based biomarkers, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), brain-derived neurotrophic factor (BDNF), metabolites (proline, alanine, tryptophan), and multi-biomarker risk score. We attempted to explain the paradoxical findings of myostatin and FGF-21 levels in relation to sarcopenia. GDF-15 levels were associated with sarcopenia prevalence but not its incidence. Plasma P3NP and BDNF levels may be biomarkers of muscle quality rather than quantity. Lower erythrocyte EPA and DHA levels were associated with slow gait speed, and erythrocyte EPA levels were associated with low handgrip strength. We developed a multi-biomarker risk score for sarcopenia and found that its accuracy in diagnosing sarcopenia was higher than that of any single biomarker.

Auer rod-positive acute leukemia with predominantly lymphoid immunophenotype: Report on 11 cases and review of literature.

Auer rods (AuRs) are prominent intracellular structures found almost exclusively in myeloid cell malignancies, such as acute myeloid leukemia (AML), chronic and juvenile myelomonocytic leukemia and myelodysplastic syndrome. Extremely rare AuRs have been reported in patients with acute lymphoblastic leukemia (ALL) or among ambiguous lineage leukemia patients with a dominantly lymphoblastic immunophenotype. We report diagnostic and follow-up data of an international cohort of 11 children suffering from leukemias with AuRs and with significant presence of T and myeloid markers, majority of whom categorized as early T-cell precursor (ETP, n=7); or T-ALL (ETP status unknown, n=2), ALAL (acute leukemia of ambiguous lineage, n=1), and AML reclassified from ALAL (n=1). We described other diagnostic details and treatment types and responses. Moreover, we summarize previously published data. Among the four patients who started and remained on ALL-type therapy, all were in the first complete remission, whereas both patients who started and remained on AML-type therapy relapsed and died. Of the patients who followed either a combined ALL/AML protocol (Interfant 06) or who switched from one of the two types of therapy to the other, one patient died, and the remaining four were in first complete remission at the most recent follow-up. We also searched for similar cases in the literature and found only three additional children with nonmyeloid leukemia and AuRs and 10 adults with this type of leukemia. Briefly, ALL- or combined ALL/AML-type therapy may be effective for treating AuR-positive leukemia patients with a lymphoid immunophenotype.

Major air pollution and climate policies in NYC and trends in NYC air quality 1998-2021.

Air pollution poses serious health risks to humans, with particular harm to children. To address the gap in understanding the efficacy of policies to reduce exposure to air pollution, we sought to assess the temporal relationship between the enactment of major air pollution and climate policies in NYC and trends in air quality during the period 1998-2021. We used previously available data from citywide monitoring and new data from the Columbia Center for Children's Environmental Health (CCCEH) longitudinal cohort studies of mothers and children living in communities in Northern Manhattan and the South Bronx. We utilized publicly available citywide air monitoring data for particulate matter (PM2.5) and nitrogen dioxide (NO2) from 2009 to 2021 from the New York City Community Air Survey (NYCCAS) database and CCCEH cohort data on residential exposure to PM2.5 and NO2 and personal exposure to polycyclic aromatic hydrocarbons (PAH) during pregnancies occurring from 1998-2016 and 1998-2021, respectively. We compared annual and overall reductions in PM2.5 and NO2 citywide and reductions in PAH concentrations in the cohort studies. As previously reported, annual average concentrations of pollutants in NYC dropped significantly over time. Between 1998 and 2021, PM2.5 and NO2 concentrations were reduced citywide by 37 and 31%, respectively. In our CCCEH cohorts, between 1998 and 2016, the annual average PM2.5 and NO2 concentrations also decreased significantly by 51 and 48%, respectively. Between 1998 and 2020, PAH concentrations decreased significantly by 66%. While it is not possible to link improved air quality to a single policy, our analysis provides evidence of a cumulative beneficial effect of clean air and climate policies enacted between 1998 and 2021 both city-wide and in our cohorts residing in communities that have been disproportionately affected by air pollution. There are important implications for health benefits, particularly for children, who are known to be especially vulnerable to these exposures. The results support further environmental and social policy changes to prevent the serious health impacts of air pollution from fossil fuel emissions.

The Comparison of Intravesical Therapy and Surgery as Treatment Options for Bladder Cancer (CISTO) study: Lessons learned about management and patient enrollment in a large, pragmatic, patient-centered trial.

The growth of patient and public involvement in clinical research highlights the paucity of literature on operational practices that ensure the success of large, patient-centered outcomes trials. The authors' objective was to identify tools launched by the Comparison of Intravesical Therapy and Surgery as Treatment Options for Bladder Cancer (CISTO) study team to determine their effectiveness in maximizing patient enrollment in this observational, pragmatic trial. The primary outcomes for this study were patient screening and enrollment across 36 CISTO study sites. The operational strategies included CISTOquestion email correspondence and All Sites Meetings, specifically poll performance data from meetings, and a nonanonymized feedback survey about the CISTO study's management practices. Effectiveness was measured using correlation analysis with patient cohort data, including screenings, enrollments, post-hoc exclusions, and the post-hoc exclusion rate. Average screenings and enrollment rose after the implementation of CISTOquestion in April 2021, with the average number of screenings rising from 7.42 to 26.8 patients per month and enrollment rising from 3.76 to 16 patients per month. Use of CISTOquestion was correlated strongly with increased patient screenings and enrollment across all study sites. Eighty-three percent of sites with above-average post-hoc exclusion rates (≥0.092) sent below the average number of CISTOquestion inquiries. Poll performance and survey data revealed that all survey respondents who used CISTOquestion found that it was a valuable and accessible resource. Of the several operational tools implemented within the CISTO study that aimed to improve patient enrollment, CISTOquestion, a centralized email for addressing eligibility questions, was most beneficial to overall patient accrual.

Reduction in the incidence of cognitive impairment and related costs through an innovative health awareness programme in rural Japan.

This study examined the impact of the Center of Healthy Aging Program (CHAP) on the cognitive function and economic burden associated with dementia. This observational study utilised Iwaki cohort data. We included participants with mini-mental state examination (MMSE) scores and categorised them into pre- and post-CHAP groups based on their year of entry into the cohort (before 2013 or after) (index year). We defined participants with suspected severe cognitive impairment and suspected mild cognitive impairment using their MMSE scores, with their incidence being the first observation meeting these definitions during the follow-up period. We compared the incidence rates between the pre- and post-CHAP groups using Cox proportional hazard analysis. Medical and caregiving costs were estimated based on the projected number of residents in Iwaki area with suspected mild cognitive impairment and sSCI during hypothetical 10 years of the CHAP implemented or not and compared. Of the 2,569 participants, 1716 and 853 were included in the pre- and post-CHAP groups, respectively. The incidence rate of suspected mild cognitive impairment was significantly lower in the post-CHAP group even after adjusted known factors associated with cognitive disorders. No cases of suspected severe cognitive impairment occurred in the post-CHAP group during the follow-up period. Estimated costs of JPY 1,628,450 (USD 11562.00 or EUR 10259.24, JPY 100 = USD 0.71 or EUR 0.63) and JPY 789,560 (USD 5605.88 or EUR 4974.23) per person per year were projected after 10 years with and without the CHAP, respectively. We demonstrated a reduction in the incidence rate of suspected mild cognitive impairment among residents who participated in the CHAP and a decrease in the medical and caregiving costs associated with suspected severe cognitive impairment.