Safety and Tolerability of Suprachoroidal Axitinib Injectable Suspension, for Neovascular Age-related Macular Degeneration; Phase I/IIa Open-Label, Dose-Escalation Trial.

Purpose: To evaluate the safety and tolerability of a single dose of axitinib injectable suspension (CLS-AX), a pan-anti-VEGF tyrosine kinase inhibitor (TKI), administered via suprachoroidal injection in patients with neovascular age-related macular degeneration (nAMD). Design: Phase I/IIa, open-label, sequential dose escalation. Participants: Anti-VEGF treatment-experienced patients with active subfoveal choroidal neovascularization secondary to nAMD. Methods: The study included 4 cohorts (0.03, 0.10, 0.50, and 1.0 mg) of approximately 5 patients each enrolled in a dose-escalating fashion. Enrolled patients received intravitreal aflibercept (2 mg) followed by a single unilateral dose of CLS-AX 1 month later. All patients were followed monthly for 3 months with the option of an additional 3 months of extended follow-up for cohorts 2 to 4. End points included systemic and ocular safety and tolerability, visual acuity, retinal thickness, and need for aflibercept therapy. Main Outcome Measures: The number of patients reporting treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), changes in ophthalmic examinations, and the number of patients qualifying for additional therapy for nAMD based on protocol-defined criteria. Results: OASIS enrolled 27 patients with nAMD with mean age of 81 years, mean duration of nAMD diagnosis of 54 months, and between 5 and 90 prior anti-VEGF treatments. Twenty-six patients completed through 3 months, with 14 entering and completing the 3-month extension. No SAEs, drug-related TEAEs, or TEAEs leading to discontinuation were observed after CLS-AX administration; there were no adverse events related to ocular inflammation, vasculitis, intraocular pressure, or dispersion of drug into the vitreous or anterior chamber. Through 6 months, stable mean best-corrected visual acuity and stable mean central subfield thickness (CST) were observed, suggestive of TKI biologic effect. No aflibercept therapy was administered up to 3 months in 58% (15/26) of patients who completed 3 months of follow-up in OASIS. In the Extension, 57% (8/14) of patients went up to 6 months without receiving aflibercept therapy. Conclusions: Up to 1.0 mg CLS-AX, a highly potent TKI targeted to the suprachoroidal space (SCS) via the SCS Microinjector, was well tolerated, with stable mean visual acuity and mean CST. A majority of patients followed for 6 months did not require aflibercept therapy. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

A heterogeneous continuous age-structured model of mumps with vaccine.

In classical mumps models, individuals are generally assumed to be uniformly mixed (homogeneous), ignoring population heterogeneity (preference, activity, etc.). Age is the key to catching mixed patterns in developing mathematical models for mumps. A continuous heterogeneous age-structured model for mumps with vaccines has been developed in this paper. The stability of age-structured models is a difficult question. An explicit formula of R 0 was defined for the various mixing modes (isolation, proportional and heterogeneous mixing) with or without the vaccine. The results show that the endemic steady state is unique and locally stable if R 0 > 1 without any additional conditions. A number of numerical examples are given to support the theory.

Evaluating the Efficacy of Immune Checkpoint Inhibitors in Elderly Patients: A Systematic Review and Meta-analysis.

In this chapter, we outline the steps for designing and conducting a rigorous systematic review and meta-analysis, focusing on the efficacy of immune checkpoint inhibitors (ICIs) in elderly patients. ICIs have improved survival rates in advanced cancers, yet their effectiveness in older populations remains unclear. We detail the essential processes involved in both systematic reviews and meta-analyses. We can evaluate the efficacy of ICIs in elderly patients with advanced cancer, examining outcomes such as overall survival and progression-free survival.

Comparison between Spectral-Domain and Swept-Source OCT Angiography for the Measurement of Persistent Hypertransmission Defects in Age-Related Macular Degeneration.

Purpose: Spectral-domain OCT angiography (SD-OCTA) scans were tested in an algorithm developed for use with swept-source OCT angiography (SS-OCTA) scans to determine if SD-OCTA scans yielded similar results for the detection and measurement of persistent choroidal hypertransmission defects (hyperTDs). Design: Retrospective study. Participants: Forty pairs of scans from 32 patients with late-stage nonexudative age-related macular degeneration (AMD). Methods: Patients underwent both SD-OCTA and SS-OCTA imaging at the same visit using the 6 × 6 mm OCTA scan patterns. Using a semiautomatic algorithm that helped with outlining the hyperTDs, 2 graders independently validated persistent hyperTDs, which are defined as having a greatest linear dimension ≥250 µm on the en face images generated using a slab extending from 64 to 400 µm beneath Bruch's membrane. The number of lesions and square root (sqrt) total area of the hyperTDs were obtained from the algorithm using each imaging method. Main Outcome Measures: The mean sqrt area measurements and the number of hyperTDs were compared. Results: The number of lesions and sqrt total area of the hyperTDs were highly concordant between the 2 instruments (rc = 0.969 and rc = 0.999, respectively). The mean number of hyperTDs was 4.3 ± 3.1 for SD-OCTA scans and 4.5 ± 3.3 for SS-OCTA scans (P = 0.06). The mean sqrt total area measurements were 1.16 ± 0.64 mm for the SD-OCTA scans and 1.17 ± 0.65 mm for the SS-OCTA scans (P < 0.001). Because of the small standard error of the differences, the mean difference between the scans was statistically significant but not clinically significant. Conclusions: Spectral-domain OCTA scans provide similar results to SS-OCTA scans when used to obtain the number and area measurements of persistent hyperTDs through a semiautomated algorithm previously developed for SS-OCTA. This facilitates the detection of atrophy with a more widely available scan pattern and the longitudinal study of early to late-stage AMD. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Exposición a temperaturas extremas y su efecto en la gestación en un departamento de Colombia / Exposure to extreme temperatures and its effect on pregnancy in a department of Colombia

Introducción: Diversas investigaciones han establecido la relación entre temperatura y duración del embarazo, la exposición a temperaturas altas durante el embarazo plantea interrogantes en especial el papel que esta juega frente a los partos prematuros y partos de bajo peso, es indispensable determinar si las temperaturas altas o bajas tienen un comportamiento protector o de riesgo sobre el feto durante la gestación en regiones tropicales. Objetivo: describir la relación entre la exposición a temperaturas altas y bajas durante el embarazo y su efecto en la edad gestacional y peso al momento del parto en los recién nacidos del departamento del Guaviare-Colombia. Metodología: Estudio tipo observacional, analítico, retrospectivo de corte transversal que busco determinar la relación entre exposición a temperaturas altas y bajas durante el embarazo y su efecto en la edad gestacional y peso al momento del parto en los recién nacidos, el universo estuvo conformado por 10.137 nacidos vivos, de los cuales 9.932 cumplieron los criterios de inclusión. Se determinó Odds Ratio para estimar la asociación entre las variables. Resultados: Dentro de la semana de retraso 3 el estar expuesto a temperaturas máximas percentil 90 es un factor protector para la ganancia ponderal de peso OR < 1, la exposición a temperaturas mínimas percentil 10 se asoció como factor protector para el parto prematuro en la semana de retraso 1 y 2 OR < 1.Conclusión: A pesar del beneficio de las altas y bajas temperaturas durante el embarazo en la ganancia ponderal de peso y disminución del parto prematuro, es recomendable prevenir la exposición a temperaturas extremas durante el periodo de gestación[AU]

Introduction: Various investigations have established the relationship between temperature and duration of pregnancy. Exposure to high temperatures during pregnancy raises questions, especially the role it plays in premature births and low-weight births. It is essential to determine whether high temperatures or low have a protective or risky behavior on the fetus during pregnancy in tropical regions.Objective: to describe the relationship between exposure to high and low temperatures during pregnancy and its effect on gestational age and weight at the time of delivery in newborns in the department of Guaviare-Colombia.Methodology:Observational, analytical, retrospective cross-sectional study that sought to determine the relationship between exposure to high and low temperatures during pregnancy and its effect on gestational age and weight at the time of delivery in newborns. The universe was made up of 10,137 births. alive, of which 9,932 met the inclusion criteria. Odds Ratio was determined to estimate the association between the variables.Results:Within the 3rd week of delay, being exposed to maximum temperatures at the 90th percentile is a protective factor for weight gain OR < 1, exposure to minimum temperatures at the 10th percentile was associated as a protective factor for premature birth in the week. of delay 1 and 2 OR < 1. Conclusion: Despite the benefit of high and low temperatures during pregnancy in weight gain and reduction in premature birth, it is advisable to prevent exposure to extreme temperatures during the gestation period[AU]

Introdução: Várias investigações estabeleceram a relação entre temperatura e duração da gravidez. A exposição a altas temperaturas durante a gravidez levanta questões, especialmente o papel que desempenha nos partos prematuros e nos nascimentos de baixo peso. É essencial determinar se as temperaturas altas ou baixas têm um comportamento protetor ou de risco para o feto durante a gravidez em regiões tropicais. Objetivo:descrever a relação entre a exposição a altas e baixas temperaturas durante a gravidez e seu efeito na idade gestacional e no peso no momento do parto em recém-nascidos no departamento de Guaviare-Colômbia. Metodologia: Estudo observacional, analítico, retrospectivo e transversal que buscou determinar a relação entre a exposição a altas e baixas temperaturas durante a gravidez e seu efeito na idade gestacional e no peso no momento do parto em recém-nascidos. O universo foi composto por 10.137 nascimentos. vivos, dos quais 9.932 preencheram os critérios de inclusão. O Odds Ratio foi determinado para estimar a associação entre as variáveis. Resultados:Na 3ª semana de atraso, a exposição a temperaturas máximas no percentil 90 é fator de proteção para ganho de peso OR < 1, a exposição a temperaturas mínimas no percentil 10 foi associada como fator de proteção para parto prematuro na semana. de atraso 1 e 2 OR < 1.Conclusão:Apesar do benefício das altas e baixas temperaturas durante a gravidez no ganho de peso e redução do parto prematuro, é aconselhável evitar a exposição a temperaturas extremas durante o período de gestação[AU]

Intravitreal faricimab for treatment naïve patients with neovascular age-related macular degeneration: a real-world prospective study.

BACKGROUND: Intravitreal faricimab, a bispecific antibody targeting both angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A), was recently introduced for the treatment of neovascular age-related macular degeneration (nAMD), diabetic macular oedema and cystoid macular oedema secondary to retinal vein occlusion. The aim of our study was to assess the efficacy, safety and durability of intravitreal faricimab in a real-world cohort of treatment-naïve patients with nAMD. METHODS: Single-centre, prospective cohort study of 21 eyes from 19 treatment-naïve nAMD patients who were treated with intravitreal faricimab from October 2022 to April 2024. Patients underwent a loading dose (LD) of 4 monthly faricimab injections followed by a treat-and-extend regimen. Primary outcomes included best-corrected visual acuity (BCVA) and structural parameters from spectral-domain optical coherence tomography (SD-OCT). Secondary outcomes included the proportion of eyes achieving a dry macula, maximal fluid-free interval and intended interval at last follow-up. RESULTS: The study included 21 eyes of 19 patients (mean age 83.1 years). After LD, 93.3% of eyes achieved a dry macular SD-OCT scan within a median time of 8 weeks. At the first extension, 53% of eyes remained dry, while 47% showed fluid recurrence. Long-term analysis (n = 14) revealed significant reductions in macular volume (MV), central subfield thickness (CST), and pigment epithelial detachment (PED) height over a median follow-up of 64.9 weeks, with sustained visual and anatomical improvements. Median BCVA, CST, and MV at the final follow-up were significantly improved from baseline (p < 0.01). The intended interval between injections was ≥ 12 weeks in 42.86% of eyes. No cases of intraocular inflammation were observed, although 10% experienced retinal pigment epithelial tears. CONCLUSIONS: Intravitreal faricimab demonstrated favourable efficacy, safety, and durability outcomes in a real-world cohort of treatment-naïve nAMD patients.

Reproductive factors and mammographic density within the International Consortium of Mammographic Density: A cross-sectional study.

BACKGROUND: Elevated mammographic density (MD) for a woman's age and body mass index (BMI) is an established breast cancer risk factor. The relationship of parity, age at first birth, and breastfeeding with MD is less clear. We examined the associations of these factors with MD within the International Consortium of Mammographic Density (ICMD). METHODS: ICMD is a consortium of 27 studies with pooled individual-level epidemiological and MD data from 11,755 women without breast cancer aged 35-85 years from 22 countries, capturing 40 country-& ethnicity-specific population groups. MD was measured using the area-based tool Cumulus. Meta-analyses across population groups and pooled analyses were used to examine linear regression associations of square-root (√) transformed MD measures (percent MD (PMD), dense area (DA), and non-dense area (NDA)) with parity, age at first birth, ever/never breastfed and lifetime breastfeeding duration. Models were adjusted for age at mammogram, age at menarche, BMI, menopausal status, use of hormone replacement therapy, calibration method, mammogram view and reader, and parity and age at first birth when not the association of interest. RESULTS: Among 10,988 women included in these analyses, 90.1% (n = 9,895) were parous, of whom 13% (n = 1,286) had ≥ five births. The mean age at first birth was 24.3 years (Standard deviation = 5.1). Increasing parity (per birth) was inversely associated with √PMD (ß: - 0.05, 95% confidence interval (CI): - 0.07, - 0.03) and √DA (ß: - 0.08, 95% CI: - 0.12, - 0.05) with this trend evident until at least nine births. Women who were older at first birth (per five-year increase) had higher √PMD (ß:0.06, 95% CI:0.03, 0.10) and √DA (ß:0.06, 95% CI:0.02, 0.10), and lower √NDA (ß: - 0.06, 95% CI: - 0.11, - 0.01). In stratified analyses, this association was only evident in women who were post-menopausal at MD assessment. Among parous women, no associations were found between ever/never breastfed or lifetime breastfeeding duration (per six-month increase) and √MD. CONCLUSIONS: Associations with higher parity and older age at first birth with √MD were consistent with the direction of their respective associations with breast cancer risk. Further research is needed to understand reproductive factor-related differences in the composition of breast tissue and their associations with breast cancer risk.

Identification of Gene Signatures Associated with COVID-19 across Children, Adolescents, and Adults in the Nasopharynx and Peripheral Blood by Using a Machine Learning Approach.

BACKGROUND: Significant variations in immune profiles across different age groups manifest distinct clinical symptoms and prognoses in Coronavirus Disease 2019 (COVID-19) patients. Predominantly, severe COVID-19 cases that require hospitalization occur in the elderly, with the risk of severe illness escalating with age among young adults, children, and adolescents. OBJECTIVE: This study aimed to delineate the unique immune characteristics of COVID-19 across various age groups and evaluate the feasibility of detecting COVID-19-induced immune alterations through peripheral blood analysis. METHODS: By employing a machine learning approach, we analyzed gene expression data from nasopharyngeal and peripheral blood samples of COVID-19 patients across different age brackets. Nasopharyngeal data reflected the immune response to COVID-19 in the upper respiratory tract, while peripheral blood samples provided insights into the overall immune system status. Both datasets encompassed COVID-19 patients and healthy controls, with patients divided into children, adolescents, and adult age groups. The analysis included the expression levels of 62,703 genes per patient. Then, 9 feature-sequencing methods (least absolute shrinkage and selection operator, light gradient boosting machine, Monte Carlo feature selection, random forest, ridge regression, adaptive boosting, categorical boosting, extremely randomized trees, and extreme gradient boosting) were employed to evaluate the association of the genes with COVID-19. Key genes were then utilized to develop efficient classification models. RESULTS: The findings identified specific markers: insulin-like growth factor binding protein 3 (downregulated in the peripheral blood of COVID-19 patients), interferon alpha-inducible protein 27 (upregulated), and SERPING1 (upregulated in nasopharyngeal tissues). In addition, fibulin-2 was downregulated in adolescent patients, but upregulated in the other groups, while epoxide hydrolase 3 was upregulated in healthy controls, but downregulated in children and adolescents. CONCLUSION: This study offers valuable insights into the local and systemic immune responses of COVID-19 patients across age groups, aiding in identifying potential therapeutic targets and formulating personalized treatment strategies.

Burden of gastrointestinal cancers among working-age population over past thirty years in China.

BACKGROUND: Although gastrointestinal (GI) cancers have been becoming a great public health concern in China, there is currently a lack of comprehensive literature on the overall burden and changing trends of GI cancers in the working-age population. AIM: To assess the burden of GI cancers and to examine the overall, age- and gender-specific trends among the working-age population in China from 1990 to 2019. METHODS: Data were extracted from the Global Burden of Disease Study 2019. The burden of GI cancers was indicated by incidence, mortality, disability-adjusted life-years (DALYs), age-standardized incidence rate (ASIR), age-standardized mortality rate, and age-standardized DALYs rate. Trends in the burden of GI cancers from 1990 to 2019 were examined using annual percent change and average annual percent change with Joinpoint regression models. RESULTS: For overall GI cancers, a declining trend was observed in the ASIR, age-standardized mortality rate, and age-standardized DALYs rate, with reductions of 0.74%, 2.23%, and 2.22%, respectively, from 1999 to 2019 in the Chinese working-age population. However, an increasing trend was observed in the ASIR for overall GI cancers from 2016-2019. The number of either incident cases, mortality cases, and DALYs was higher for colon/rectum cancer and liver cancer in younger participants but lower for esophageal, gallbladder, biliary tract, pancreatic, and stomach cancer among older subjects. Moreover, sex disparity in the GI cancers burden was also examined over 30 years. CONCLUSION: The total burden of GI cancers remained heavy among the working-age population in China, although declining trends were observed from 1999 to 2019. Disparities in the GI cancers burden existed between sexes, age groups, and cancer types. Population-based precision prevention strategies are needed to tackle GI cancers among working-age individuals, considering the age, sex, and cancer type disparities in China.

The multiple faces of autoimmune Addison's disease in children.

Primary adrenal insufficiency (PAI) is a rare medical condition, characterized by a deficiency in adrenal hormones. Although rare, PAI is a life-threatening disease requiring prompt recognition and treatment. However, symptoms of PAI are often non-specific and diagnosis can be challenging, causing frequent diagnostic delays. In adults, autoimmunity is the most common cause of PAI in industrialized countries, whereas in children, the most frequent etiology is represented by congenital defects of steroidogenesis and, in particular, by congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. A few recent case series from different countries have reported that autoimmunity is the second most common etiology of PAI in the pediatric age group. However, data on autoimmune PAI in children are still scant and the exact epidemiology, clinical manifestations, and long-term outcomes of this condition have yet to be defined. The scope of this review is to summarize the current knowledge on the etiology, presentation, and treatment of autoimmune PAI in childhood and to increase physicians' awareness of the signs that should raise an early suspicion of this condition.

Perinatal mortality among term births: Informing decisions about singleton early term births in Western Australia.

BACKGROUND: To minimise the risk of perinatal mortality, clinicians and expectant mothers must understand the risks and benefits associated with continuing the pregnancy. OBJECTIVES: Report the gestation-specific risk of perinatal mortality at term. METHODS: Population-based cohort study using linked health data to identify all singleton births at gestations 37-41 weeks, in Western Australia (WA) from 2009 to 2019. Lifetable analysis was used to combine the risk of each type of perinatal mortality and calculate the cumulative risk of perinatal mortality, termed the perinatal risk index (PRI). Rates of antepartum and intrapartum stillbirth and neonatal death, as well as the PRI, were examined for each gestational week at term by non-Aboriginal and Aboriginal ethnicity. For non-Aboriginal women, rates were also examined by time-period (pre- vs. post-WA Preterm Birth Prevention Initiative (the Initiative) rollout), primiparity, and obstetric risk. RESULTS: There were 332,084 singleton term births, including 60 perinatal deaths to Aboriginal mothers (3.2 deaths per 1000 births to Aboriginal mothers) and 399 perinatal deaths to non-Aboriginal mothers (1.3 deaths per 1000 births to non-Aboriginal mothers). For non-Aboriginal women, the PRI was at its lowest (PRI 0.80, 95% CI 0.61, 1.00) at 39 weeks gestation. For Aboriginal women, it was at its lowest at 38 weeks (PRI 2.43, 95% CI 0.48, 4.39) with similar risk at 39 weeks (PRI 2.68, 95% CI 1.22, 4.14). The PRI increased steadily after 39 weeks gestation. The risk of perinatal mortality was higher among Aboriginal women. The gestation-specific perinatal mortality rates were similar by the time-period, primiparity and obstetric risk. CONCLUSIONS: The gestational ages at term associated with the lowest risk of perinatal mortality reinforce that the recommendation not to deliver before 39 weeks without medical indication is applicable to both Aboriginal and non-Aboriginal women giving birth in WA. There was no increase in the perinatal mortality rate associated with the introduction of the Initiative.

Evaluating the updated LATE-NC staging criteria using data from NACC.

INTRODUCTION: Limbic-predominant age-related TAR DNA-binding protein of 43 kDa encephalopathy neuropathologic change (LATE-NC) staging criteria were updated in 2023. We evaluated this updated staging using National Alzheimer's Coordinating Center data. METHODS: We examined associations of LATE-NC stages with cognition and other neuropathologic changes (NCs), and with cognition while accounting for other NCs, using multilevel regression models. RESULTS: Of 1352 participants, 502 (37%) had LATE-NC (23% stage 1a, 6% stage 1b, 58% stage 2, 13% stage 3). LATE-NC stages were associated with cognition, hippocampal sclerosis of aging (HS-A), Alzheimer's disease NC (ADNC), Lewy bodies (LBs), and hippocampal atrophy. While stage 1b was associated with cognition and HS-A consistent with other stages, it was not associated with ADNC or LBs. All LATE-NC stages remained significantly associated with worse cognition when accounting for other NCs. DISCUSSION: The updated LATE-NC staging criteria capture variations in early TDP-43 pathology spread which are consequential for cognition and associations with other NCs. HIGHLIGHTS: We applied the updated limbic-predominant age-related TAR DNA-binding protein of 43 kDa encephalopathy neuropathologic change (LATE-NC) staging criteria to data from the National Alzheimer's Coordinating Center. LATE-NC stage 1b was identified in 22% of participants with stage 1. In contrast to other LATE-NC stages, stage 1b was not associated with Alzheimer's disease neuropathologic change (ADNC) or Lewy bodies. Stages 1a and 1b were significantly associated with dementia and memory impairment. Stages 1b+ were more strongly tied to dementia than all other neuropathologic changes except high likelihood ADNC.

Socio-demographic and other factors contributing to excessive leisure screen time in preadolescent children.

OBJECTIVES: Excessive screen use in early school age is associated with worsened health habits and negative child development in later age. We aimed to assess the time spent on modern and traditional screen-based devices and examine its associations with socio-demographic characteristics. METHODS: This population-based cross-sectional observation study was conducted in Czechia, Slovakia and Finland between April and June 2021. Participants (N = 1,915) were parents/caregivers of children attending elementary school grades 1 to 3, selected by stratified random sampling. Children's daily leisure screen time (LST) based on parental reports was the main outcome. Descriptive statistics, mean comparison and linear regression analysis were used for the analysis. RESULTS: The average daily LST was found to be as high as 3.5 hours and significantly associated with most socio-demographic variables. Eighty percent of children exceeded the threshold of two hours of LST per day, which was formerly introduced by the American Academy of Pediatrics. The most important predictor of LST in children was having their screen-based device(s) for their exclusive personal use (EPU). Linear regression with all predictors assessed together confirmed the significant effect of the screen-based devices' EPU, the child's sex and grade, the child's birth order and the parent's education, even when controlled for media parenting practices. CONCLUSIONS: Given the widespread availability of smartphones for exclusive personal use among young children, the regulation of EPU and the reinforcement of effective media parenting practices, particularly in families with lower education and income, are critical public health strategies to mitigate the negative impact of excessive screen time on child development and overall well-being.

Temporal Trends in Racial and Gender Disparities of Early Onset Colorectal Cancer in the United States: An Analysis of the CDC WONDER Database.

BACKGROUND: The mortality rates of early-onset colorectal cancer (EOCRC) have surged globally over the past two decades. While the underlying reasons remain largely unknown, understanding its epidemiology is crucial to address this escalating trend. This study aimed to identify disparities potentially influencing these rates, enhancing risk assessment tools, and highlighting areas necessitating further research. METHODS: Using the CDC Wide-Ranging Online Data for Epidemiologic Research (WONDER) database, this study assessed EOCRC mortality data from 2012 to 2020. Individuals under 50 years who succumbed to EOCRC were identified through the International Classification of Diseases, Tenth Revision (ICD-10) codes. Data interpretation and representation were performed using R 4.2.2 software. RESULTS: Between 2012 and 2020, EOCRC mortality rates fluctuated marginally between 1.7 and 1.8 per 100,000. Male mortality rates increased from 1.9 to 2.0 per 100,000, while female rates varied between 1.5 and 1.6 per 100,000. Significant variations were observed across age groups, with the 40-49 years category experiencing an increase from 6.34 (2012) to 6.94 (2020) per 100,000. Racial category-based data revealed the highest mortality rates among African Americans. Geographically, Mississippi and Alabama exhibited elevated mortality rates. Age-adjusted mortality rate (AAMR) assessments indicated a marked decline for both genders from 2012 to 2020, with consistently higher rates for men. CONCLUSION: The findings highlight the evolving landscape of EOCRC mortality, revealing significant gender, age, and racial disparities. These results underscore the urgent need for tailored health strategies and intensified research efforts targeting these disparities.

Age Is Just a Number? The Impact of Age on Abdominoplasty Outcomes: A Single Surgeon Experience.

BACKGROUND: Abdominoplasty is among the most popular aesthetic procedures in plastic surgery worldwide. Common indications include prior massive weight loss, surgical or not, with remaining skin excess and post-pregnancy women looking to restore their youthful abdominal contour. Aging of the worldwide population results in a greater number of older patients interested in aesthetic procedures. Identifying the impact of age on abdominoplasty outcomes is crucial in ensuring the safety of care and determining sub-optimal patients that might not benefit from the procedure. MATERIALS AND METHODS: Medical records of all abdominoplasty patients operated by the senior author were screened for appropriate patients. Patients were excluded from the study if the mandatory follow-up time was not met or in instances of incomplete medical records. Patients were further stratified into 5 age groups based on age and compared using pre-operative, intra-operative and post-operative characteristics. Further regression analysis was performed to estimate the risk of complications for each individual age group, in an unadjusted and adjusted model. RESULTS: Six hundred and seventy-three patients were included in the study. Statistically significant differences were noted between the groups in respect smokers, prior bariatric surgery, and hypertension, diabetes mellitus and dyslipidemia (p values <0.01). Seroma rates, were greatest in the oldest age group (P value = 0.039). Odds ratio of 3.3 was calculated for seroma development in patients aged greater than 60. In a multivariate analysis, the risk diminished and was found to be statistically insignificant. CONCLUSION: Abdominoplasty is a safe procedure in all age groups. Increased rates of specific complications must be assessed in relation to potential confounders that exist between different age groups. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Secondary Analysis Assesses Dietary Diversity Changes among Maya Guatemalan Women Post-Nutrition Interventions.

OBJECTIVES: This study aimed to evaluate the change in the Dietary Diversity (DD) Index of Maya women of reproductive age living in rural areas of the Western Highlands of Guatemala after nutrition, health, and agroecology interventions. METHODS: This is a secondary analysis study on DD from two matched groups from three villages in the Lake Atitlan area in the department of Sololá. The first cohort was recruited in 2017 (sample of n = 77). The second cohort was recruited in 2020 (sample of n = 61). Both were followed until 2021. The program provided various resources for assistance for food production and home improvements (sessions from 2018 to 2022). Agroecology sessions were conducted in the test farm. Due to the COVID-19, adjustments were made to continue the education and training sessions. RESULTS: Both cohort samples had a statistically significant increase in participants who consumed at least 15 g from five groups of foods (2017: p = .00002; 2020: p = .045). There was a statistically significant increase in mean food groups consumed daily (2017: p < .00001; 2020: p = .005). CONCLUSIONS FOR PRACTICE: Implementing interventions that include nutrition, health, and agroecology practices in the long term has demonstrated a statistically significant increase in the Dietary Diversity Index of Maya women in their reproductive years living in rural villages in the Western Highlands.

Neonatal outcomes after in utero exposure to antipsychotics: a systematic review and meta-analysis.

Adverse neonatal outcomes following in utero antipsychotic exposure remain unclear. This systematic review and meta-analysis aimed to investigate associations between in utero first- and second-generation antipsychotic exposure and various neonatal outcomes. The primary outcome was small for gestational age. Secondary outcomes included other birth weight-related measures, prematurity and neonatal outcomes. MEDLINE, EMBASE, CENTRAL, ICTRP, and ClinicalTrials.gov were searched for on 8th July 2023. Two reviewers independently selected studies reporting associations between exposure and neonatal outcomes (all designs were eligible, no language or time restriction) and extracted data. ROBINS-I was used for risk of bias assessment. Meta-analyses were performed. Measures of association were odds ratios and mean differences. Thirty-one observational studies were included. Regarding small for gestational age < 10th percentile, meta-analysis was only performed for second-generation antipsychotics and showed no evidence for an association (OR 1.31 [95%CI 0.83; 2.07]; I²=46%; phet=0.13, n = 4 studies). First-generation antipsychotics were associated with an increased risk of small for gestational age < 3rd percentile (OR 1.37 [95%CI 1.02; 1.83]; I²=60%; phet=0.04, n = 5) and a lower mean birthweight (MD -135 g [95%CI -203; -66]; I²=53%; phet=0.07, n = 5). Second-generation antipsychotics were associated with large for gestational age > 97th percentile (OR 1.56 [95%CI 1.31; 1.87]; I²=4%; phet=0.37, n = 4) and Apgar score < 7 (OR 1.64 [95%CI 1.09; 2.47]; I²=47%; phet=0.13, n = 4). Both types of antipsychotics were associated with increased risks of preterm birth and neonatal hospitalization. Despite potential confounding in the studies, this systematic review and meta-analysis showed that newborns of mothers using antipsychotics during pregnancy are potentially at risk of adverse neonatal outcomes. Data sources: MEDLINE, EMBASE, CENTRAL, ICTRP, ClinicalTrials.gov. Prospero Registration Number CRD42023401805.

Hypertension in India: a gender-based study of prevalence and associated risk factors.

BACKGROUND: Hypertension, a major non-communicable disease, is responsible for a significant number of global deaths, including approximately 17.9 million yearly. The Global Burden of Disease 2019 (GBD 2019) estimates that 19% of global deaths are attributed to elevated blood pressure. India, with a population of over 1.4 billion, is facing a serious challenge in combating this silent killer. This study aims to analyze the gender-based prevalence of hypertension in India and explore its associated risk factors using data from the fifth National Family Health Survey (NFHS-5). METHODS: NFHS-5 collected data from 636,699 households across all states and union territories. The study includes standardized blood pressure measurements for 17,08,241 individuals aged 15 and above. The data were analyzed using Stata, employing descriptive statistics for the assessment of the prevalence and binary logistic regression to identify predictors of hypertension. RESULTS: The study found the overall prevalence of hypertension in India to be 22.6%, with men (24.1%) having a higher prevalence than women (21.2%). Prevalence increased with age, reaching 48.4% in individuals aged 60 and above. Urban residents had a slightly higher prevalence (25%) than rural residents (21.4%), indicating the rapid spread of hypertension across all populations. Regional variations were observed, with the highest prevalence in Sikkim (37.9%) and the lowest in Rajasthan (16.5%). Increasing age, urban residence, belonging to certain religions (Muslim and other than Hindu or Muslim), and being classified as Scheduled Tribes (ST) were associated with a higher likelihood of hypertension. Conversely, belonging to Scheduled Castes (SC) or Other Backward Classes (OBC), being currently unmarried, and having higher education were associated with a lower likelihood of hypertension. Wealth index analysis revealed that those in the richest quintile were more likely to have hypertension. Behavioural risk factors, such as alcohol consumption, overweight, obesity, increased waist circumference, and high blood glucose levels, are positively associated with hypertension. CONCLUSION: Hypertension is a significant health burden in India, affecting both men and women. Age is the strongest non-modifiable predictor for both men and women. However, ageing women have higher odds of hypertension than ageing men, and this distinction becomes much more evident in their older ages. Obese women, based on BMI, have higher odds of hypertension than men. However, hypertension prevalence is slightly higher among men who are overweight or obese compared to women. BMI, waist circumference, random glucose level, alcohol use, and education level emerged as major predictors. Health education and awareness campaigns are critical to control the growing burden of hypertension in India. Policymakers must focus on preventive measures, targeting lifestyle changes and improved healthcare access for both men and women. By addressing these risk factors, India can make significant progress in controlling hypertension and reducing its impact on public health.

Dihuangzicao Granules Regulate the AGE/RAGE/NF-κB Signaling Pathway to Inhibit Inflammation in Psoriatic Mice via Network Pharmacology and Experimental Validation.

AIM: Psoriasis is an immune-mediated skin disease that occurs worldwide and is characterized by high prevalence and chronicity. Psoriasis has a complex pathogenesis and is difficult to cure. Therefore, continuous exploration of the pathogenesis of psoriasis and the search for new drug treatment methods are crucial for improving treatment efficiency and reducing psychological damage to psoriasis patients. The active ingredients in Dihuang Zicao granules (DHZCG) can effectively treat psoriasis. Therefore, this study aimed to analyze the active ingredients of DHZCG and their potential mechanisms for treating psoriasis. METHODS: The effective components of DHZCG were screened via the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Genetic information for psoriasis was retrieved from the GeneCards, OMIM and DisGENET databases. Protein-Protein Interaction (PPI) analysis was performed, and component‒target‒disease networks were constructed. Important molecular biological processes and signaling pathways were screened via GO and KEGG analyses. Molecular docking of the active ingredients and key targets was performed via AutoDock Vina (1.1.2). A mouse model of psoriasis was established and divided into a control group, model group, low-dose DHZCG group (L-DHZCG), medium-dose DHZCG group (M-DHZCG), and high-dose DHZCG group (H-DHZCG). Hematoxylin and Eosin (HE) staining was performed to determine the pathological changes in the skin of each group of mice, and the Psoriasis Area Severity Index (PASI) score was used to assess skin damage. ELISA and RT‒ PCR were used to measure the levels of the inflammatory factors TNF-a, IL-17A, and IL-23 in the serum and skin tissue of the mice, respectively. Western blotting was used to analyze the expression of proteins related to the AGE/RAGE signaling pathway. Immunofluorescence was used to examine the expression of the inflammatory factor NF-kB. Immunohistochemistry was used to measure IL-1ß and TNF-a expression in skin tissues. RESULTS: Sixty genes associated with psoriasis treatment by DHZCG, including core genes encoding IL-6, TNF-a, AKT1, IL-1ß, TP53, NFKB1, BCL2, and MAPK3, were identified. Through the construction of a psoriasis mouse model, DHZCG treatment effectively reduced skin damage and significantly decreased the levels of the validated factors TNF-a, IL-17A, IL- 23, IL-1b, and NF-kB in the serum and damaged skin. Furthermore, the reduction in the levels of these inflammatory factors by DHZCG is associated with the downregulation of the AGE/RAGE signaling pathway. CONCLUSION: DHZCG reduces inflammation and alleviates psoriasis by downregulating the AGE/RAGE/NF-kB signaling pathway. This study is beneficial for providing a theoretical basis for the development of drugs for psoriasis and for offering personalized treatment strategies for the clinical management of psoriasis.

Reactivation of stable neovascular age-related macular degeneration following treat-and-extend regimen discontinuation.

BACKGROUND: To describe the incidence and pattern of reactivation of neovascular age-related macular degeneration (nAMD) following successful treatment with treat-and-extend intravitreal anti-vascular endothelial growth factor therapy. METHODS: Consecutive patients with treated nAMD who did not require further treatment over a 6-month period and who attended their 3-monthly optical coherence tomography monitoring clinic in Moorfields Eye Hospital from 1 November 2019 to 31 January 2020 were included. Patients with diagnoses of macular neovascularization other than AMD, and patients with incomplete data were excluded. Baseline demographics recorded were age, sex, race, laterality, cause of macular neovascularization, drug, number of injections, and duration of treatment. Date, setting, symptoms, and time to retreatment were collected among patients with disease reactivation. RESULTS: The medical records of 286 patients were included. Most patients were female (64.3%), white (68.18%), and were receiving aflibercept monotherapy (55.2%). Mean number of injections at baseline was 17.79 ± 11.74 (range 3-62) with a mean treatment duration of 39.47 ± 30.68 months (range 2-139). Reactivation of AMD was identified in 32.2% of cases with 87% of recurrences identified via scheduled visit. The most common symptom was blurring of vision in 44.6%, while 39.1% were asymptomatic. Mean time from baseline to retreatment was 29.37 ± 22.40 months (range 5-104), with 20.7%, 73.9% and 88.04% of these patients requiring retreatment within 1, 3, and 5 years, respectively. CONCLUSIONS: Despite prior treatment with no reactivation in 6 months, 32.2% reactivate, 73.9% of which within 3 years. A significant proportion, 39.1%, reactivated without symptoms necessitating regular monitoring in the first 5 years.