Death Rate Research Articles

EFFECT OF DAPAGLIFLOZIN ON CARDIOVASCULAR OUTCOMES IN HFREF PATIENTS: IMPACT OF DIABETES MELLITUS TYPE 2 STATUS

Dapagliflozin has shown promise in the treatment of heart failure with reduced ejection fraction (HFrEF), but its effects in patients with and without diabetes remain unclear. Objective: This study aimed to assess the effects of dapagliflozin in HFrEF patients, both with and without diabetes. Methods: From January to July 2023, a six-month case-control study was conducted in the cardiology department of a Tertiary Care Hospital in Peshawar, Pakistan. All patients received an additional dose of dapagliflozin (10 mg) alongside their usual treatment plans. The primary outcome was a composite of heart failure exacerbation or cardiovascular death. Data analysis was performed using SPSS version 22. Results: Patients with diabetes mellitus type 2 (DMT2) exhibited a higher rate of cardiovascular death (22%) and hospitalization for heart failure (14.4%) compared to those without diabetes. The hospitalisation rate for heart failure was also higher in the DMT2 group (12.21%) than in the non-diabetic group (8.6%). Over the trial period, cardiovascular death occurred in 12.44% of patients with DMT2 compared to 7.30% in those without DMT2. Patients with diabetes experienced a significantly higher number of first and recurrent hospitalizations for heart failure and cardiovascular death compared to those without diabetes (32.45% vs. 19.20%, p=0.021). Conclusion: Dapagliflozin therapy in HFrEF patients demonstrated varying effects between those with and without diabetes. The study underscores the importance of personalised management strategies considering comorbid medical conditions. Despite dapagliflozin treatment, patients with both heart failure and diabetes continued to experience cardiovascular complications, highlighting the need for individualised treatment plans that account for a patient's complete medical profile.

Outcomes of Pregnancies in Women with Congenital Heart Disease: A Study in a Tertiary Care Hospital in Bangladesh

Background: Pregnancies in individuals with congenital heart disease (CHD) frequently pose complex challenges. The presence of CHD elevates the risks not only for the expectant mother but also for the well-being of the developing fetus. Additionally, careful monitoring and specialized medical care are crucial throughout the pregnancy to ensure the best possible outcomes for both. Objective: This study was aimed to assess the outcomes of pregnancies in women with congenital heart disease. Methods: This was a cross-sectional observational study that was conducted in the Combined Military Hospital (CMH), Dhaka, Bangladesh from January 2020 to December 2021. A total 30 pregnant women with congenital heart disease were enrolled through purposive sampling. All the demographic and clinical information was recorded. Data were processed, analyzed, and disseminated by using MS Office tools. Results: Among participants, Lower Segment Cesarean Section (LSCS) was the most common delivery (43.3%), followed by vaginal delivery (36.7%). Instrumental delivery, specifically through outlet forceps, was found in 6.7% of cases. Pregnancy termination occurred in 6.7% due to inevitable abortion and 3.3% for medical reasons, resulting in one maternal death (3.3%). Perinatal outcomes included 90% live births and 81.5% with Apgar scores ≥9. Neonatal Intensive Care Unit (NICU) admission was required for 33.3%, with a 3.3% perinatal death rate. Conclusions: In pregnant women with congenital heart diseases, common delivery modes are Lower Segment Cesarean Section (LSCS) and vaginal delivery. Termination and maternal fatality rates are low. Perinatal outcomes are generally positive, with most births resulting in live infants with Apgar scores ≥9 and high newborn survival rates, although some require Neonatal Intensive Care Unit (NICU) admission. J Rang Med Col. March 2024; Vol. 9, No. 1: 50-54

Using the Lagrange Interpolation Polynomial Method to calculate the prevalence of coronavirus disease 2019 (COVID-19) in Turkey

The goal of this paper is to look into a numerical approximation for the spread of the coronavirus disease 2019 (COVID-19) in Turkey. From March 11th to November 30th, all data is examined one by one for this purpose. The Lagrange interpolation method does not require evenly spaced x values. On the other hand, it is usually preferable to look for the closest value in the table and then use the lowest-order interpolation that is consistent with the functional form of the data. Using this method, a function for monthly and general data on the number of COVID-19 disease deaths and cases infected with the disease is obtained. Matlab programming is used to obtain Lagrange interpolation polynomials. Simulations for month by month and general data are obtained using Lagrange interpolation polynomial. The rate of spread of disease and death numbers is obtained by taking the first derivative of this function. Monthly and general tables are constructed for this propagation rate data. Peak point of the disease and different change values ​​are determined from the information in these simulations. The rates of death and spread of the disease by months are compared. As a result of this comparison, it can be seen in which months the rate of spread of disease and death increases and decreases. Monthly increase and decrease values ​​can be seen from the Figure 3-Figure 6. For example, a relative decrease can be observed in April and May

Epidemiological, Clinical and Therapeutic Aspects of Neuropaediatric Emergencies in Children Aged 1 Month to 15 Years in the Paediatric Emergency Department of CHU-Gabriel Toure

Introduction: Paediatric neurological emergencies are a major public health problem worldwide, in Africa and in Mali. Despite the scale and complexity of paediatric neurological emergencies, there is little data in the literature in Africa and particularly in Mali on these neurological disorders in paediatrics. Aim: The aim of our study was to examine the epidemiological, clinical and therapeutic aspects of neuropaediatric emergencies in children aged between 1 month and 15 years in the paediatric department of the CHU-Gabriel Touré in 2021. Patients and Methods: This was a cross-sectional study conducted over a twelve-month period (01 January to 31 January 2021) in children aged 1 month to 15 years hospitalised in the paediatric emergency department for a neurological emergency. Results: The frequency of hospitalization was 18.35%. The age group 12 to 60 months accounted for 43.7%. The sex ratio was 1.44. Convulsion was the most frequent reason for hospitalisation (49.3%). Delayed psychomotor development was noted in 4%. Around 3% of the children had not been vaccinated. On clinical neurological examination, the signs observed were : Altered consciousness (88.3%), convulsion (61%), and axial hypotonia (29%). Focal convulsions accounted for 59%, and 45.7% were febrile. The main diagnoses were neuromalaria, hyperpyretic convulsion and meningitis (68.3%, 7% and 6.3% respectively). The death rate within the first 24 hours was 48%. The average length of hospitalisation was 5.03 +/-4.5 days, with extremes of 1 and 21 days. Conclusion: Neuropaediatric emergencies are a major paediatric health problem. They are frequent and contribute substantially to infant and child mortality in our context.

Cytokine profiling in 128 patients with transient abnormal myelopoiesis: a report from the JPLSG TAM-10 trial

AbstractTransient abnormal myelopoiesis (TAM) occurs in 10% of neonates with Down syndrome (DS). Although most patients show spontaneous resolution of TAM, early death occurs in ∼20% of cases. Therefore, new biomarkers are needed to predict early death and determine therapeutic interventions. This study aimed to determine the association between clinical characteristics and cytokine levels in patients with TAM. A total of 128 patients with DS with TAM enrolled in the TAM-10 study conducted by the Japanese Pediatric Leukemia/Lymphoma Study Group were included in this study. Five cytokine levels (interleukin-1b [IL-1b], IL-1 receptor agonist, IL-6, IL-8, and IL-13) were significantly higher in patients with early death than in those with nonearly death. Cumulative incidence rates (CIRs) of early death were significantly associated with high levels of the 5 cytokines. Based on unsupervised consensus clustering, patients were classified into 3 cytokine groups: hot-1 (n = 37), hot-2 (n = 42), and cold (n = 49). The CIR of early death was significantly different between the cytokine groups (hot-1/2, n = 79; cold, n = 49; hot-1/2 CIR, 16.5% [95% confidence interval (CI), 7.9-24.2]; cold CIR, 2.0% [95% CI, 0.0-5.9]; P = .013). Furthermore, cytokine groups (hot-1/2 vs cold) were independent poor prognostic factors in the multivariable analysis for early death (hazard ratio, 19.25; 95% CI, 2.056-180.3; P = .010). These results provide valuable information that cytokine level measurement was useful in predicting early death in patients with TAM and might help to determine the need for therapeutic interventions.

Comparisons of energy metabolism and personality traits before and after angling in crucian carp (Carassius auratus)

Catch and release has become a very popular fish conservation strategy and fisheries management tool. The physiological and behavioral changes in individuals who experience catch and release may be adaptive. These individuals may exhibit more cautious bait use or hook avoidance behavior when faced with lures again. Here, our study was conducted on crucian carp (Carassius auratus) to compare energy metabolism and personality (e.g. activity) before and after angling for three bouts of repeated angling. Our study showed that the standard metabolic rate, maximum metabolic rate, aerobic scope and factorial aerobic scope were all lower after three bouts of repeated angling, and the metabolic rates were greater before angling than after angling in the first two bouts of angling. In addition, the total magnitude of excess postexercise oxygen consumption after repeated angling also showed a decreasing trend as the number of angled bouts increased. The percentage of time spent moving increased after three bouts of repeated angling, but there were no changes in either individual swimming speed or total distance traveled. Our results suggest that repeated angling causes a high death rate and decreases the aerobic/anaerobic metabolic capacity of crucian carp, which may reduce their metabolic potential for other physiological functions, such as locomotion, growth and digestion. Future studies should continue to focus on the effects of fishing on the physiology, behavior, and population dynamics of fish.

Abstract PO2-23-12: Innovative Metastatic Breast Cancer Therapy, CBT300, Reverses Drug and Immune Resistance

Abstract For many patients with metastatic breast cancer (MBC), their disease is treatable but incurable. Although the rate of death from MBC has significantly decreased over the last 10 years due to early detection and new treatment options, MBC still accounts for over 40,000 deaths each year in the US that has been consistent for the past 30 years. Recently, it is estimated that 90% of those deaths were due to drug resistant recurrent disease. Nearly 45% of MBC deaths can be attributed to a subpopulation of patients with metastatic triple negative breast cancer (mTNBC). Despite MBC’s initial sensitivity to chemotherapy, it often recurs at greater than 40% in stage I-III patients and greater than 80% in stage IV patients which have a dismal 5-year survival of 12%. African American women have a 40% greater incidence of death from MBC despite a 4% lower risk of diagnosis. Unfortunately, current therapies do little to reduce drug resistance and death for recurrent drug resistant MBC. Currently, the only therapies approved by the FDA for recurrent TNBC patients are Keytruda plus chemotherapy and an Antibody Drug Conjugate (ADC) called Sacituzumab Govitecan. Keytruda (anti-PD-L1) is an immune checkpoint inhibitor(ICI) given with chemotherapy (nab-paclitaxel, paclitaxel, or gemcitabine plus carboplatin). The second recently approved therapy, Sacituzumab Govitecan (SG), is composed of an antibody to human trophoblast cell-surface antigen 2 (Trpo-2) coupled to SN-38 (topoisomerase I inhibitor). Although these results are very encouraging, the 80% of TNBC patients that either do not have high positive PD-L1 tumors, or don’t respond to these therapies and become drug resistant suggests that most patients with TNBC will have recurrent disease with little or no hope for survival. For contrast, our novel MBC therapy, CBT300, targets cell surface GRP78 that has been found in over 95% of MBC and in 93% of TNBC tumors. We can now show that inhibition of cell surface GRP78 can a) induce apoptosis of drug resistant TNBC cells in vitro and in vivo, b) eliminate drug resistance showing synergistic effects with chemotherapy in vitro and in vivo, c) decrease amount of chemotherapy in combination with CBT300 and d) reduce immune suppression. Recent publications show that GRP78 is found on many types of tumor cell surfaces but not on normal cell surfaces. In fact, tumor cell surface GRP78 (csGRP78) is important for many aspects of MBC development, including cell survival, proliferation, chemoresistance, angiogenesis, metastasis formation, immune suppression, and stem cell formation. Recently, it has been shown that increased cell surface GRP78 expression in TNBC patients was significantly associated with later stage, increased distant metastasis, increased aggressiveness, shorter disease-free survival, and decreased overall survival. In studies to help understand how cell surface GRP78 causes MBC progression and drug resistance, we discovered a novel GRP78 binding transmembrane protein on TNBC cells called Receptor Tyrosine Kinase Orphan Receptor-1 (ROR1). Using the GRP78 binding domain from ROR1 and a human Fc IgG1 domain, we created a biologic fusion protein that is a potent and cell surface specific GRP78 inhibitor, CBT300. We now show that CBT300’s elimination of cell surface GRP78 destabilizes and removes oncofetal proteins ROR1, Cripto-1, and checkpoint protein PD-L1 from tumor cell surfaces resulting in reversal of chemoresistance, reduction in immune suppression, inhibition of stem cell phenotype and increased tumor cell apoptosis. Since ROR1, Cripto-1 and PD-L1 are three of the major redundant pathways for tumor drug resistance, immune suppression and stem cell formation, the ability to inhibit all these pathways with CBT300, a single safe and very efficacious therapy, is very innovative and could be a significant advance for the treatment of MBC. Citation Format: Elizabeth Stolarik, Jorryn Zelek, Mariah Thigpen, Anita Davidson, Donald Davidson. Innovative Metastatic Breast Cancer Therapy, CBT300, Reverses Drug and Immune Resistance [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-23-12.

Mortality from the 1944–1945 famine in Java, Indonesia

AbstractThis article examines the human toll of the 1944–1945 famine in Java, Indonesia's main island. It estimates birth and death rates for the Indonesian population in Java during 1941–1951. Using the net population loss method, the article approximates a net loss of 3.3 million people during the 1942–1945 Japanese occupation period. This includes 1.8 million excess deaths; 0.7 million during 1944 and 1.1 million during 1945. The remainder are 1.4 million missing births in 1944 and 1945, associated with the malnutrition of women of childbearing ages and physical separation of wives from husbands recruited by Japanese authorities for forced labour.

FREQUENCY OF EARLY STENT THROMBOSIS (ACUTE AND SUBACUTE) IN PATIENTS PRESENTING WITH ACUTE ST ELEVATION MYOCARDIAL INFARCTION (STEMI) UNDERGOING PRIMARY PERCUTANEOUS CORONARY INTERVENTION (PCI)

Sudden cardiac stent thrombosis (ST) is a severe clinical risk that can lead to high fatality rates. However, data are scarce on the prevalence of early ST events following ‘primary percutaneous coronary intervention’ (pPCI) and the characteristics that predict it, particularly among Pakistani patients. Objective: The objective is to determine possible indicators and evaluate ‘the frequency of acute and sub-acute stent thrombosis’ (ST) after ‘primary percutaneous coronary intervention’ (PCI). Methods: Five hundred individuals who had undergone primary PCI were enrolled from July 2022 to December 2023. Telephone follow-up assessments were used to gather information on 30-day results, including death rates, recurrence of symptoms, and episodes of ST. ‘ST was classified as acute’ (occurring ‘during the procedure’) or ‘sub-acute’ (‘occurring within 30 days post-procedure) using standardised criteria established by the ‘Academic Research Consortium. Results: In this study, 500 patients were enrolled, primarily male (80.4%, 362 patients). ‘Stent thrombosis’ (either acute or sub-acute) was observed in 6.8% of patients, with 10.1% (4) classified as definite ST and the remaining 91.9% (34) as probable ST. Male patients were more prevalent among those who developed ST, along with a higher incidence of hypertension, diabetes, reduced left ventricular ejection fraction (LVEF) pre-PCI, and higher Killip Class. Patients with ST experienced a higher in-hospital mortality rate compared to those without ST, with a p-value of 0.02. Notably, ‘Killip Class’ (‘III-IV’) emerged as ‘an independent ST predictor in this patient cohort. These findings underscore the importance of risk assessment and vigilant management, particularly in patients presenting with higher Killip Class and other associated risk factors, to mitigate ST occurrence and adverse outcomes following primary PCI. Conclusion: Early stent thrombosis (ST) appears relatively common in patients undergoing primary PCI. Those with diabetes and hypertension face an elevated risk of ST, while patients presenting in ‘Killip Class III-IV’ demonstrate an ‘independent predictive’ factor for early ST.

The burden of alcohol-related cardiovascular complications in young and middle-aged adults: rising burden of atrial fibrillation and hypertensive heart disease

Background and Aims The burden of alcohol-related complications is high and rising. However, there are notable deficiencies in comprehensive epidemiological study focusing on cardiovascular complications from alcohol, especially among young and middle-aged adults. We thus aimed to determine the burden of these conditions in young and middle-aged adults globally. Methods and Results We used data from the Global Burden of Disease Study 2019 and analysed the mortality and disability-adjusted life years of alcohol-associated cardiovascular complications in young and middle-aged adults. The findings were classified by sex, region, country, and Sociodemographic Index (SDI). The highest age-standardized death rates (ASDR) were observed in stroke 0.84 (95% UI 0.60–1.09), followed by alcoholic cardiomyopathy 0.57 (95% UI 0.47–0.66) per 100,000 population. The overall burden of alcohol-associated cardiovascular complications decreased globally but increased in atrial fibrillation and hypertensive heart disease. Regionally, most regions underwent a decrease in ASDR, but an increase was observed in Southeast Asia (+2.82%), Western Pacific (+1.48%), low-middle (+1.81%), and middle SDI (+0.75%) countries. Nevertheless, the ASDR and ASDALYs were highest in Europe. Conclusions The impact of alcohol-associated atrial fibrillation and hypertensive heart disease has increased over the last decades. Regarding region, the burden in Europe and the rising burden in Asia, require immediate public health policy to lessen these cardiovascular complications from alcohol in young and middle-aged adults.

Abstract PO5-09-09: Incidence of Breast Cancer in Hispanic Women Across the US: A Focus on Texas

Abstract Introduction Breast cancer (BC) is one of the most common cancers affecting the female population in the United States, particularly among the Hispanic community. According to the CDC, the incidence rate of new breast cancer cases in Hispanic women is 95.6 per 100,000 annually, and the mortality rate is 13.7 per 100,000 women annually. Texas is home to one of the largest Hispanic communities in the US. By analyzing the prevalence, mortality, and access to healthcare services in Texas, we can shed light on the unique aspects of breast cancer within the Hispanic population. Overall, this study will provide valuable insights and identify potential avenues for reducing disparities and improving healthcare outcomes for Hispanic women affected by breast cancer. Materials and methods This study used comparative data from State Cancer Profiles on the CDC and NIH databases. The database was used to generate an overall comparison of breast cancer in Hispanic women across different US states. Comparison factors analyzed include incidence, mortality, insurance, and screening efforts. Significant differences were noted especially in Texas. Graphs and quantitative data for comparison factors were generated. This data is from 2015-2019 unless noted. Results The incidence of breast cancer in Hispanic women in Texas (TX) is 93.5 (Age-Adjusted Incidence Rate-cases per 100,000) with a CI of (92.2-94.8). The incidence of BC in Hispanic women in the US averages 99.0 with a CI of 98.7-99.9. From the incidence data, Hispanic women in Texas have a lower overall incidence of BC compared to the rest of the Hispanic females in the US. When analyzing the mortality rate, Hispanic women in TX have an Age-Adjusted Death Rate (deaths per 100,000) of 15.2 (CI of 14.7-15.8). In the US, Hispanic women have an Age-Adjusted Death Rate (deaths per 100,000) of 13.0 (CI of 13.4-13.9). To analyze preventative measures, a graph reporting mammogram use in 2020 by state was gathered. In TX 2020, the estimated age-adjusted prevalence of mammograms among Hispanic females from 50-74 years old was 75.0% (CI of 67.0%-81.7%). Nationally, the age-adjusted prevalence among Hispanic females 50-74 years who reported mammogram screening in 2 years was 79.7% (CI of 76.6 – 82.4). As for Texas insurance rates in 2020, Hispanic women under 65 years old, 27.4 % reported being uninsured. In comparison, other ethnicities such as African American (non-Hispanic) women, 16.5% reported to be uninsured, and white (non-Hispanic) women in Texas 11.8 % reported to be uninsured. Additionally, to further analyze if the lack of preventative measures was causing women to have a higher mortality rate, the instance of late-stage diagnosis of BC in Texan Hispanic women was analyzed. The age-adjusted incidence rate of late-stage breast cancer in Hispanic women was reported to be 33.4 (CI of 32.6-34.2) and the national incidence of late-stage BC in Hispanic women is 35.0 (CI of 35.1-35.8). Conclusion Even with Texas having one of the largest Hispanic communities, Hispanic women with breast cancer in Texas are faced with obstacles that lead to an increase in their mortality rate. As seen in the results, Hispanic women have less incidence of BC (including late stage) than their equivalent across the US but Hispanic women in TX have higher mortality rates in comparison. This is additionally accompanied by a decrease in insured women and a decrease in the utilization of cancer screenings. Lack of access to affordable healthcare and lack of regulatory cancer screenings cause Hispanic women to meet their premature death. Further analysis of the effects of affordable health care or further molecular investigation of this population is encouraged to research to fully conclude the reason behind this population's disparities. Citation Format: Catalina Esguerra, Kemely Santos Barbosa, Roy Khalife, Anthony Magliocco. Incidence of Breast Cancer in Hispanic Women Across the US: A Focus on Texas [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-09-09.

Abstract PO1-16-11: Real-world features and outcomes of young advanced breast cancer (ABC) patients (pts) from RegistEM (GEICAM/2014-03) study

Abstract Background: BC is the most incident cancer worldwide in < 40 years old (y) women. Increasing body mass index and changes in reproductive history contribute to the growing incidence of premenopausal BC. A higher proportion of luminal B-like and estrogen receptor negative (ER─) tumors, an increased risk of early relapse, and more unfavorable longer-term outcomes for young women with ER+ tumors when compared to older women, have been reported. In this analysis, we focus on age-specific BC characterization from a real-world population-based perspective. Methods: Pts were enrolled in the non-interventional and ambispective RegistEM study in ABC diagnosed between 2016 and 2019. We describe the features and outcomes of < 50 y pts at their initial BC diagnosis according to their BC subtype. BC subtypes were based on the most recent tumor tissue sample (distant metastasis, and in its absence, primary BC). Comparisons between < 40 and ≥ 50 y groups were performed. Results: Pts < 50 y represent 39% (n=685) of total pts with available data (n=1739, any age group) in the registry. By age, 12% (n=212) were < 40y, and 27% (n=473) 40-49y. At first BC diagnosis, 75% and 25% pts had early BC (EBC) and de novo metastatic BC (MBC), respectively. In EBC pts, stage II (50%) and III (28%) were the most frequent at diagnosis; invasive non-special type carcinoma was the predominant morphology, and grade 2 was the most common histological grade, but grade 3 was predominant in TN pts and HER2+ < 40y pts. The median time to recurrence was < 2y in TN pts, 3y in HER2+ pts, and 6y in luminal HER2─ pts. At ABC diagnosis, the median age was 47y, all pts were female but one, 98% white, and 60% premenopausal (94% were premenopausal at EBC diagnosis). A family history of BC and/or ovarian cancer was reported in 34% pts, and a hereditary-risk genetic test was performed in 39% (254 of 652) pts; 12% (n=30) had BRCA1/2 mutations, with a proportion higher in TN pts (9 of 33, 27%) vs. luminal HER2─ (21 of 183, 12%) and HER2+ (0 of 38) pts. Visceral disease was the most frequent in all subgroups, highlighting statistical differences (p=0.022) between age groups ( < 40y 55% vs. ≥50y 71%) only in TN pts. 60% had ≤ 2 locations involved, similarly in all subgroups. The presence of >2 metastatic locations was statistically higher in HER2+ pts ≥50y (54%) vs both < 40y (32%) and 40-49y (48%). Brain disease was more present at ABC diagnosis in TN (9%) and HER2+ (7%) than in luminal HER2─ (3%). Median no. of treatment lines (L) was 3 (range 0-11), and median follow-up 44 mo (95% CI: 41-44). 99% pts received 1L, the distribution of treatments by BC subtype within each age subgroup was similar; median duration of 1L was 21 months (mo) in luminal HER2─, 17 mo in HER2+, and 5 mo in TN pts. 68% of pts who received 1L, reached 2L. Duration of 2L dropped dramatically: 8 mo in luminal HER2─, 6 mo in HER2+, and 2 mo in TN pts. No differences between ≥50y and the rest of pts were observed in PFS for any treatment line. 49% pts had died at the database cut-off date (05-April-23), with no differences between age groups, but TN pts had the highest death rate (80%). Additional data according to BC subtypes and age groups are in the table. Conclusions: Luminal HER2─ was the predominant BC subtype in all age subgroups. Visceral disease was more prevalent in young TN pts compared to older pts. TNBC pts experienced a shorter median time to recurrence and the highest mortality rate regardless of age, compared to HER2+ and luminal HER2- pts, indicating the need for targeted interventions in this subgroup. Citation Format: Sara López-Tarruella, Angel Guerrero, Isabel Álvarez, Silvia Antolin Novoa, Ariadna Tibau, Josefina Cruz, César A Rodríguez, Purificación Martínez, J. Ignacio Chacón, María Hernández, Mireia Margelí, Encarna Adrover, Catalina Falo, Iria González, Álvaro Rodríguez-Lescure, María Marín, César Gómez, Juan de la Haba-Rodríguez, J. José Illaramendi, Raquel Andrés, Andrea Blasco, Mª José Escudero, Susana Bezares, Federico Rojo. Real-world features and outcomes of young advanced breast cancer (ABC) patients (pts) from RegistEM (GEICAM/2014-03) study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-16-11.

Preventable Premature Deaths from the Five Leading Causes of Death in Nonmetropolitan and Metropolitan Counties, United States, 2010-2022.

A 2019 report quantified the higher percentage of potentially excess (preventable) deaths in U.S. nonmetropolitan areas compared with metropolitan areas during 2010-2017. In that report, CDC compared national, regional, and state estimates of preventable premature deaths from the five leading causes of death in nonmetropolitan and metropolitan counties during 2010-2017. This report provides estimates of preventable premature deaths for additional years (2010-2022). 2010-2022. Mortality data for U.S. residents from the National Vital Statistics System were used to calculate preventable premature deaths from the five leading causes of death among persons aged <80 years. CDC's National Center for Health Statistics urban-rural classification scheme for counties was used to categorize the deaths according to the urban-rural county classification level of the decedent's county of residence (1: large central metropolitan [most urban], 2: large fringe metropolitan, 3: medium metropolitan, 4: small metropolitan, 5: micropolitan, and 6: noncore [most rural]). Preventable premature deaths were defined as deaths among persons aged <80 years that exceeded the number expected if the death rates for each cause in all states were equivalent to those in the benchmark states (i.e., the three states with the lowest rates). Preventable premature deaths were calculated separately for the six urban-rural county categories nationally, the 10 U.S. Department of Health and Human Services public health regions, and the 50 states and the District of Columbia. During 2010-2022, the percentage of preventable premature deaths among persons aged <80 years in the United States increased for unintentional injury (e.g., unintentional poisoning including drug overdose, unintentional motor vehicle traffic crash, unintentional drowning, and unintentional fall) and stroke, decreased for cancer and chronic lower respiratory disease (CLRD), and remained stable for heart disease. The percentages of preventable premature deaths from the five leading causes of death were higher in rural counties in all years during 2010-2022. When assessed by the six urban-rural county classifications, percentages of preventable premature deaths in the most rural counties (noncore) were consistently higher than in the most urban counties (large central metropolitan and fringe metropolitan) for the five leading causes of death during the study period.During 2010-2022, preventable premature deaths from heart disease increased most in noncore (+9.5%) and micropolitan counties (+9.1%) and decreased most in large central metropolitan counties (-10.2%). Preventable premature deaths from cancer decreased in all county categories, with the largest decreases in large central metropolitan and large fringe metropolitan counties (-100.0%; benchmark achieved in both county categories in 2019). In all county categories, preventable premature deaths from unintentional injury increased, with the largest increases occurring in large central metropolitan (+147.5%) and large fringe metropolitan (+97.5%) counties. Preventable premature deaths from CLRD decreased most in large central metropolitan counties where the benchmark was achieved in 2019 and increased slightly in noncore counties (+0.8%). In all county categories, preventable premature deaths from stroke decreased from 2010 to 2013, remained constant from 2013 to 2019, and then increased in 2020 at the start of the COVID-19 pandemic. Percentages of preventable premature deaths varied across states by urban-rural county classification during 2010-2022. During 2010-2022, nonmetropolitan counties had higher percentages of preventable premature deaths from the five leading causes of death than did metropolitan counties nationwide, across public health regions, and in most states. The gap between the most rural and most urban counties for preventable premature deaths increased during 2010-2022 for four causes of death (cancer, heart disease, CLRD, and stroke) and decreased for unintentional injury. Urban and suburban counties (large central metropolitan, large fringe metropolitan, medium metropolitan, and small metropolitan) experienced increases in preventable premature deaths from unintentional injury during 2010-2022, leading to a narrower gap between the already high (approximately 69% in 2022) percentage of preventable premature deaths in noncore and micropolitan counties. Sharp increases in preventable premature deaths from unintentional injury, heart disease, and stroke were observed in 2020, whereas preventable premature deaths from CLRD and cancer continued to decline. CLRD deaths decreased during 2017-2020 but increased in 2022. An increase in the percentage of preventable premature deaths for multiple leading causes of death was observed in 2020 and was likely associated with COVID-19-related conditions that contributed to increased mortality from heart disease and stroke. Routine tracking of preventable premature deaths based on urban-rural county classification might enable public health departments to identify and monitor geographic disparities in health outcomes. These disparities might be related to different levels of access to health care, social determinants of health, and other risk factors. Identifying areas with a high prevalence of potentially preventable mortality might be informative for interventions.

Paxlovid TM reduces the incidence of pneumonia, hospitalization, and death in a cohort of COVID-19 patients from northeast Mexico

BackgroundInformation on PaxlovidTM effectiveness must be monitored and updated in real world scenarios. Our research question was what is the effectiveness of PaxlovidTM in adult patients with COVID-19? Therefore, we investigated the effectiveness of PaxlovidTM on reducing the incidence of pneumonia, hospitalization, and mortality in a cohort of COVID-19 positive adult patients from northeast Mexico. MethodsA retrospective cohort study of COVID-19 positive adult patients from Nuevo Leon, Mexico from December 2020 to May 2023 (after Omicron BA-5 circulation) was performed. Paxlovid™ use was authorized in September 2022. Therefore, we analyzed effectiveness in patients with confirmed diagnosis who met selection criteria between September 2022 and May 2023 (n = 20,799; 5,673 with and 15,126 without PaxlovidTM). ResultsThe pneumonia (0.1% vs. 0.4%, p < 0.0001), hospitalization (0.1% vs. 1.2%, p < 0.0001), and death rates (0.04% vs. 0.2%, p < 0.0001) were lower in patients with PaxlovidTM treatment independently of age, sex, comorbidity, and COVID-19 and pneumococcal vaccination history. Effectiveness was 88.2%, 95.9% y 91.9% for pneumonia, hospitalization, and death, respectively. ConclusionsPaxlovidTM reduces the presentation of pneumonia, hospitalization, and death secondary to COVID-19. It is recommended to continue monitoring PaxlovidTM effectiveness, as other SARS-CoV-2 variants continue to emerge.

The role of pre-onset hair hormone in predicting the prognosis of patients with severe pneumonia and acute COVID-19 outbreak

Numerous research works have investigated the potential impact of endocrine hormones on the severity of COVID-19-related pneumonia in individuals. However, there are few studies on the effect of pre-onset neuroendocrine hormones on the prognosis of COVID-19 patients. This study looked into the prognostic value of pre-onset hair hormone levels in COVID-19 infected individuals. This study included 27 patients with COVID-19 and collected patient information and laboratory indicators. The hormone levels in hair were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Within 28 days, 63 % of the patients in this study passed away. With 28-day mortality as the outcome index, urea nitrogen, CURB-65 score and pneumonia severity score (PSI) of 2 groups were statistically significant (P < 0.05). Among all hormone levels detected in hair, only progesterone level was substantially correlated negatively with COVID-19 patients' 28-day mortality(P < 0.05). The level of progesterone in hair was substantially adversely connected with the death rate at 28 days of COVID-19 patients, according to correlation and logistic regression analysis(P < 0.05). Among patients with COVID-19 pneumonia, hair progesterone levels were strongly associated with 28-day mortality, which emphasizes hair progesterone's importance as a prognostic factor.

Disaggregating Death Rates of Age-Groups Using Deep Learning Algorithms

Reliable estimates of age-specific vital rates are crucial in demographic studies, while ages are, in most cases, commonly grouped in bins of five years. Indeed, public health and national systems require single age-specific data to achieve accurate social planning. This paper introduces a deep learning approach for splitting the abridged death rates, providing a more comprehensive perspective on the indirect age-specific vital rates estimation from grouped data. Additionally, we contribute to the existing literature by introducing a multi-population (countries and genders) approach, providing reliable estimates considering the heterogeneity of longevity dynamics over age, years, and across populations. We also contribute to the state of the art in indirect estimation by introducing, for the first time, a multi-population indirect estimation leveraging subnational data. Our model accurately captures mortality dynamics by age over time and among different populations. We prove the model’s ability to estimate reliable predictions of age-specific mortality rates by also studying how the hyperparameters’ choice affects the model reliability and analyzing the age-specific relative differences between the real and the estimated mortality rates.

Prostate cancer, its implications and awareness in the South Asian population: a retrospective cross-sectional cohort analysis

Introduction: The second most frequent form of cancer in males and the main reason for cancer-related deaths worldwide is prostate cancer (PC). Despite being less common than in Western nations, PC incidence and death rates have been rising throughout South Asia. This study intends to evaluate how well-informed and knowledgeable the South Asian public is about PC, its symptoms, and screening procedures among men and women. Methods: From August to September of 2022, a cross-sectional survey was carried out throughout South Asia. Participants in the research had to be at least 24 years old, and it used a practical sampling approach. A self-created questionnaire with both closed- and open-ended questions was used to gather the data. SPSS was used to conduct statistical analysis, including χ 2 tests for relationships. Results: A total of 378 individuals, comprising 57.6% men and 41.8% women, were involved in the study. Only 45.0% of participants were aware of prostate specific antigen testing for early PC diagnosis, however, 81.7% of people recognized what the prostate gland was. Approximately 87% of individuals had never received a screening for PC. Compared to males, women showed a stronger understanding of PC and its screening techniques. Notably, 94.7% believed the likelihood of effective therapy was increased by early identification. Conclusion: While women demonstrated better levels of knowledge, the study’s findings show that the general population in South Asia suffers from a serious shortage of reliable knowledge concerning PC. To promote early identification, lower morbidity, and enhance treatment success, awareness-raising and educational initiatives are essential, with a focus on both sexes. This study establishes the foundation for future research and emphasizes the necessity for targeted educational programmes in the area.

Selection of urban flood shelter locations based on risk assessment

Within the framework of global climate change, there is a recurring occurrence of floods and waterlogging disasters, which pose significant risks to human lives and overall safety. The phenomenon of urbanization has led to an increased vulnerability of cities to flood disasters. Evacuation serves as a viable strategy for adapting to climate change, managing intense precipitation events, and mitigating the impact of flood disasters. Hence, the meticulous choice of shelters has emerged as a crucial element in enhancing the effectiveness of evacuations. Nevertheless, the process of choosing shelters sometimes neglects to consider the potential for flooding and has not undergone thorough testing. Hence, the objective of this research is to systematically choose shelters within the central metropolitan region, incorporate flood risk considerations into the shelter site model, and assist cities in mitigating the consequences of floods resulting from climate change. To begin with, employ a two-dimensional shallow water model in order to replicate instances of intense precipitation and produce data on flood inundation. Subsequently, the simulation results are utilized to assess the flood risk using the entropy weight approach. This risk is then incorporated into the multi-objective optimization model to determine the optimal shelter placement. Ultimately, the ABM model was employed to create a simulation of crowd evacuation in urban areas, confirming the efficacy of shelter selection and thoroughly examining the influence of various shelters on the efficiency of community emergency evacuation. The study's findings indicate that a total of 26 shelters were chosen within the study area using a multi-objective methodology, ensuring the inclusion of all affected populations. The utilization of multi-objective models in the selection of shelter places has been shown to enhance evacuation efficiency, as confirmed by the ABM model. The simulation findings indicate a decline in the population's death rate from 1.94% to 0.98%, an increase in the evacuation rate from 97.4% to 98.4%, and a reduction in the number of casualties by 133 individuals.

An eco-friendly and cost-effective HPTLC method for quantification of COVID-19 antiviral drug and co-administered medications in spiked human plasma

The coronavirus-2 has led to a global pandemic of COVID-19 with an outbreak of severe acute respiratory syndrome leading to worldwide quarantine measures and a rise in death rates. The objective of this study is to propose a green, sensitive, and selective densitometric method to simultaneously quantify remdesivir (REM) in the presence of the co-administered drug linezolid (LNZ) and rivaroxaban (RIV) in spiked human plasma. TLC silica gel aluminum plates 60 F254 were used as the stationary phase, and the mobile phase was composed of dichloromethane (DCM): acetone (8.5:1.5, v/v) with densitometric detection at 254 nm. Well-resolved peaks have been observed with retardation factors (Rf) of 0.23, 0.53, and 0.72 for REM, LNZ, and RIV, respectively. A validation study was conducted according to ICH Q2 (R1) Guidelines. The method was rectilinear over the concentration ranges of 0.2–5.5 μg/band, 0.2–4.5 μg/band and 0.1–3.0 μg/band for REM, LNZ and RIV, respectively. The sensitivities of REM, LIN, and RIV were outstanding, with quantitation limits of 128.8, 50.5, and 55.8 ng/band, respectively. The approach has shown outstanding recoveries ranging from 98.3 to 101.2% when applied to pharmaceutical formulations and spiked human plasma. The method’s greenness was assessed using Analytical Eco-scale, GAPI, and AGREE metrics.

Insights into novel inhibitors intending HCMV Protease a computational molecular modelling investigation for antiviral drug repurposing

Human cytomegalovirus (HCMV) is an important opportunistic pathogen that is the most significant viral cause of congenital birth abnormalities and is responsible for a high morbidity and death rate in immunocompromised patients. HCMV's rising severity and the limitations of current vaccines in preventing infection highlight the urgent need for effective antiviral drugs. This study aimed to identify small compounds using extensive & appropriate in-silico drug design techniques, including molecular docking, Post-docking MM-GBSA, ADMET, MD simulation, PCA, and DCCM were employed in this study capable of binding to the viral protease and inhibiting its activity, thereby preventing proteolytic processing during capsid maturation. 3516 compounds from life chemical were used in molecular docking, and the top four compounds having high binding affinity and promising ADMET properties with life chemicals ID: F3407-0101 (CID: 49667672), F6559-3323 (CID: 121022124), F6456-1266 (CID: 71810903), and F3411-7969 (CID: 50785034). MD simulation was also used to assess the stability of the protein-ligand complex structure. Finally, after MD simulation, principal component analysis (PCA), and dynamic cross-correlation matrix (DCCM) analysis were performed using trajectories, and we can suggest the best drug candidate which is CID: 50785034 (N-(3-fluoro-4-methylphenyl)-2-({7-oxo-8-[(oxolan-2-yl) methyl]-5-thia-1,8,10,11-tetraazatricyclo [7.3.0.0ˆ {2,6}] dodeca-2(6),3,9,11-tetraen-12-yl}sulfanyl)acetamide), another two compounds CID: 121022124, and CID: 71810903 which comes after CID: 50785034. All three compounds may have the potential to be developed as a therapy option for HCMV infection.