Substantial Burden Research Articles

An examination of caregiver burden and contributing factors in cases of congenital microtia deformity.

This study aimed to assess the burden and influencing factors among primary caregivers of children with congenital microtia. A total of 153 primary caregivers of children with congenital microtia who underwent auricular reconstruction surgery at a tertiary A-grade hospital in Xi'an between October 2019 and August 2022, were recruited using convenience sampling. The Zarit Caregiver Burden Interview (ZBI) was employed to evaluate caregiver burden. While convenience sampling allowed for the practical recruitment of participants, its limitations include potential selection bias, which may affect the generalizability of the results. The mean total ZBI score was 30.07 ± 12.29. Among the participants, 26 caregivers (17.0%) reported no burden, 102 caregivers (66.7%) reported mild burden, 22 caregivers (14.4%) reported moderate burden, and 3 caregivers (2.0%) reported severe burden. Multivariate regression analysis identified several significant factors influencing caregiver burden, including the location and severity of the lesion, educational level, method of medical payment, monthly household income, communication with others about the child's condition, caregiver self-blame or guilt, and family support (all P < .05). Primary caregivers of children with congenital microtia face substantial burdens, emphasizing the need for targeted healthcare interventions. Strategic approaches are essential to address the psychological, social, and financial challenges they encounter. Future research should focus on longitudinal studies and interventions to enhance caregiver well-being and patient outcomes. However, caution is advised when generalizing these findings due to the sampling limitations.

Cardiodiabesity: Epidemiology, resource and economic impact

ObjectiveTo assess i) the epidemiology of cardiodiabesity, ii) its association with healthcare resource utilization and cost of care, as well as iii) provide recommendations for its management. MethodsA cohort study of insured adults with early-stage and/or active cardiodiabesity from January 2019 to December 2021 identified through a longitudinal, and de-identified medical and pharmacy claims database was conducted. All patients were followed for one year through December 2022. Conditions include cardiovascular disease, prediabetes, Type 2 diabetes (T2D), chronic kidney disease (CKD), overweight and/or obesity. Rates of progression from early-stage cardiodiabesity to active cardiodiabesity and/or advanced cardiodiabesity with complications; frequency of emergency department, inpatient and outpatient visits; as well as total cost of care over one year were analyzed. ResultsA total of 3,273,813 and 1,628,407 patients had at least one of the comorbid conditions for early-stage and active cardiodiabesity, respectively. Among those with all early-stage cardiodiabesity conditions, 27.4 % progressed to active cardiodiabesity, while 88.4 % of those with all active cardiodiabesity conditions progressed to complications within one year. Predictors of progression from early-stage to active cardiodiabesity were hypertension (OR: 2.31, 95 % CI: 2.29–2.33, p < 0.001), hyperlipidemia (OR: 1.77, 95 % CI: 1.76–1.79, p < 0.001), CKD stages 1 and 2 (OR: 1.74, 95 % CI: 1.69–1.79, p < 0.001), prediabetes (OR: 1.64, 95 % CI: 1.63–1.66, p < 0.001) and living in areas with very high social needs (OR: 1.25, 95 % CI: 1.23–1.26, p < 0.001). Significant predictors of progression from active cardiodiabesity to complications were T2D (OR: 1.88, 95 % CI: 1.81–1.96, p < 0.001), CVD (OR: 1.47, 95 % CI: 1.44–1.51, p < 0.001), CKD stages 3 and 4 (OR: 1.37, 95 % CI: 1.34–1.41, p < 0.001) and obesity (OR: 1.29, 95 % CI: 1.26–1.32, p < 0.001). Average total cost of care increased significantly among those who progressed from one disease phase to the next (p < 0.05). ConclusionsCardiodiabesity is deadly and rapidly progressive with substantial economic burden on the healthcare system. However, it is preventable. Innovative approaches to better understand the holistic impact of cardiodiabesity on total cost of care, early intervention or management to halt disease progression and promote equity, as well as decrease resource utilization are needed.

Efficacy and Safety of Upadacitinib vs Dupilumab in Adults and Adolescents with Moderate-to-Severe Atopic Dermatitis: Week 16 results of an Open-label, Randomized, Efficacy Assessor-Blinded Head-to-Head Phase 3b/4 Study (Level Up).

Atopic dermatitis (AD) is a chronic skin disease characterized by intense itch and eczematous skin lesions. Some patients continue to experience flares and substantial clinical burden despite ongoing systemic treatment. This study assessed the efficacy and safety of once-daily upadacitinib (UPA), initiated at 15 mg and dose-escalated to 30 mg based on clinical response, compared with dupilumab (DUPI) per its label. Week 16 primary analysis results are presented. Level Up is a phase 3b/4 global, randomized, open-label, efficacy assessor blinded study evaluating UPA vs DUPI in adolescents and adults with moderate-to-severe AD who had inadequate response to systemic therapy or when use was inadvisable. Patients were randomized to UPA or DUPI for 16 weeks of treatment (Period 1). Patients on UPA started on 15 mg and were dose-escalated to 30 mg if they did not achieve an Eczema Area and Severity Index reduction of at least 50% (EASI 50) or a ≥4-point Worst Pruritus Numerical Rating Scale (WP-NRS) improvement on/after Week 4, or EASI 75 on/after Week 8. The primary endpoint was simultaneous achievement of EASI 90 and WP-NRS 0/1 at Week 16. Ranked secondary endpoints included skin and itch responses at varying response levels and timepoints. Safety measures were assessed throughout the study. Superior efficacy in achieving simultaneous EASI 90 and WP-NRS 0/1 response at Week 16 was demonstrated with UPA vs DUPI (19.9% vs 8.9%, respectively; p<0.0001). UPA showed superiority vs DUPI for all ranked secondary endpoints, with post-hoc analyses exhibiting higher itch response rates as early as Day 2. No new safety signals were identified during this period. Treatment of moderate-to-severe AD with UPA, initiated at 15 mg and dose escalated based on clinical response, demonstrated superiority vs DUPI per its label for the primary endpoint of simultaneous achievement of near complete skin clearance (EASI 90) and little to no itch (WP-NRS 0/1) at Week 16, with all ranked secondary endpoints demonstrating superiority at varying skin and itch response levels and timepoints. There were no new safety signals identified compared to the previously reported safety profiles of UPA and DUPI.

"They Have to Make an Effort Too": What Decliners Can Teach Us About HIV Cure/Remission-Related Clinical Trials? Results from a French Qualitative Study.

Only one study to date has focused on people living with HIV (PLWH) who refused to participate in a HIV cure/remission-related clinical trial (HCCT)-"decliners" hereafter-that included analytical treatment interruption (ATI). Exploring why these persons refuse may provide valuable information to ensure more ethical recruitment and support in HCCTs within the bigger picture of improving HIV cure research. The qualitative component of the AMEP-EHVA-T02/ANRS-95052 study, called AMEP-Decliners, documented the experiences of French PLWH who refused to participate in EHVA-T02/ANRS-VRI07, a phase II randomized, placebo-controlled HCCT with ATI. AMEP-Decliners comprised semi-structured individual interviews with six decliners in two HIV care sites in France between September 2022 and March 2023. The interviews documented their expectations regarding HCCTs, reasons for refusal, and perceived factors that might have led them to participate. Audio files were transcribed, and an inductive thematic analysis was performed. Surprisingly, the main reason for refusal was not ATI but the trial monitoring. Besides the frequency of appointments, respondents emphasized the incompatibility with their active life. One underlying reason for refusal was that participating would have meant "break[ing] the carefree attitude about the disease," reflecting the substantial psychological burden associated with participation. Finally, respondents perceived that the trial's clinical team did not sufficiently recognize their "normal life" and the level of commitment required to participate, leading them to call for greater involvement by the team: "they have to make an effort too." Results from decliners' discourses highlighted that two levels of commitment to participation must be considered when developing HCCTs: psychological burden and logistical constraints. We suggest allowing home examinations and flexible appointment times, prioritizing face-to-face invitations in order to address the psychological burden associated with HCCT participation, and explaining the reasons for monitoring constraints when they cannot be alleviated. Further studies are necessary to confirm our results.

Enablers and barriers to dietary change for Māori with nutrition-related conditions in Aotearoa, New Zealand: a scoping review.

Māori, the Indigenous population of Aotearoa New Zealand, face a substantial burden of nutrition-related diseases, especially obesity and type 2 diabetes. Weight loss, through dietary change, is a central component of obesity and diabetes prevention and management; however, most approaches have not been designed with or evaluated specifically for Māori. The aim of this study was to review literature on the enablers and barriers to dietary change, for Māori. Relevant literature published from January 2000 to May 2024 was identified by searches in Medline (Ovid), Embase (Ovid), Scopus, Indigenous health (informit), CINAHL (EBSCO), Web of Science and NZResearch. Studies included Māori and reflected enablers and barriers to dietary change for individuals/whānau (families). Data identifying the aims, methods, interventions, location, population studied and identified enablers and barriers to dietary change and responsiveness to Māori were extracted. Enablers and barriers to dietary change were mapped to a New Zealand indigenous health framework, the Meihana model. Settings included studies based in Aotearoa New Zealand, where participants were free living and able to determine their dietary intake. Studies included at least 30% Māori participants. Twenty two of 77 identified records met the inclusion criteria. Records included a diverse range of research approaches. Using a relevant Indigenous model, this study highlights that multiple and diverse enablers and barriers to dietary change exist for Māori and the critical importance of developing interventions, in close partnership with Indigenous communities, grounded in Indigenous understandings of health.

Economic burden of short-acting beta-2 agonist (SABA) overuse among asthma patients in Türkiye: a cost analysis with respect to the updated GINA treatment recommendations.

This cost of illness study aimed to determine economic burden of short-acting β2-agonist (SABA) overuse in Türkiye from payer perspective with respect to the updated GINA 2022 treatment recommendations. A total of 3,034,879 asthma patients comprised the study population, via estimations extrapolated from the Türkiye arm of the global SABINA III study. The economic burden (costs related to the drug use and severe exacerbations) was compared in subgroups of overall (≥ 0 canisters/year) vs. GINA-recommended (0-2 canisters/year, hypothetical population) SABA use and in subgroups of appropriate use (0-2 canisters/year, real population) vs. overuse (≥ 3 canisters/year) of SABA with extrapolation of SABINA Türkiye data to the Türkiye asthma population. Recommended SABA use was predicted to prevent 127,505 of 157,512 severe exacerbations per year in mild asthma patients and 2,668,916 of 3,262,800 severe exacerbations per year in moderate-severe asthma patients. Annual cost burden of not applying recommended SABA use (overall [≥ 0 canisters/year] vs. GINA-recommended [0-2 canisters/year] SABA use) in mild asthma and moderate-severe asthma patients was calculated to be €20.43 million and €427.65 million in terms of severe exacerbations, and to be €829,352 and €7.20 million in terms of drug costs, respectively. The total annual economic burden arising from not applying recommended SABA use was estimated to be €456.11 million. Appropriate use (0-2 canisters/year) vs. overuse (≥ 3 canisters/year) of SABA was associated with decreased frequency of severe exacerbations per year in mild asthma (from 129,878 to 27,634) and moderate-severe asthma (from 2,834,611 to 428,189) patients. SABA overuse in mild and moderate-severe asthma patients was estimated to yield an additional annual cost of €16.38 million and €385.59 million, respectively in terms of severe exacerbations, and a total €11.30 million additional drug cost. The overall annual economic burden arising from SABA overuse was estimated to be €413.27 million. The estimated annual total economic burden arising from not applying recommended SABA use (€456.11 million) and SABA overuse (€413.27 million) with respect to the updated GINA 2022 treatment recommendations indicates the substantial cost burden of SABA overuse to the Turkish National Health System, corresponding up to 26% of the total direct cost of asthma reported in our country.

Psoriasis: a disease beyond the skin.

Psoriasis is a chronic, immune-mediated inflammatory dermatosis with a multifactorial etiology, affecting approximately 3% of the Italian population. This condition not only imposes a substantial burden on physical health but also significantly diminishes the personal and social quality of life of affected individuals. This study aims to assess the critical role of integrated management approaches in psoriasis, focusing specifically on the role of primary care physicians in coordinating multidisciplinary care and addressing comorbidities. A comprehensive review of current therapeutic guidelines, classification systems, and available treatment strategies was conducted. This was supplemented with real-world clinical case studies. The study evaluated intervention approaches at both primary and secondary care levels, involving collaborations between general practitioners and specialists. Special emphasis was placed on the use of clinical assessment tools such as the Psoriasis Area and Severity Index (PASI) to categorize disease severity and guide therapeutic decisions. Our findings underscore the effectiveness of a multidisciplinary and personalized approach in managing psoriasis, particularly in moderate-to-severe cases. The pivotal role of primary care physicians in the early diagnosis, ongoing monitoring, and coordination of care pathways was highlighted, leading to significant improvements in comorbidity management. The clinical cases presented illustrate how tailored therapeutic regimens, supported by close collaboration between general practitioners and dermatologists, can result in the effective resolution of psoriatic lesions and markedly enhance patients’ quality of life. This study reinforces the necessity of a comprehensive, integrated, and multidisciplinary approach in the management of psoriasis, with primary care physicians serving as crucial intermediaries between community-based and specialist care. Depending on disease severity, treatment response, and recurrence patterns, primary care physicians play a central role in directing patients to appropriate secondary care services. The integration of specialist dermatological care with ongoing community-based monitoring optimizes clinical outcomes and mitigates the overall disease burden. We advocate for the establishment of clinical networks that facilitate seamless communication between different levels of care, ensuring holistic and targeted management of both psoriasis and its associated comorbidities. Keywords: Psoriasis, primary care physician, multidisciplinary care, integrated therapy, quality of life, comorbidities.

Peer support groups and care burden in hemodialysis caregivers: a RCT in an Iranian healthcare setting

BackgroundChronic renal failure poses a significant global health challenge, exerting a substantial burden on both patients and their caregivers. Hemodialysis, a common treatment for end-stage renal disease, imposes extensive physical, emotional, and financial pressures on caregivers, often leading to a high care burden. This study uniquely examines the impact of peer support groups on reducing the care burden among caregivers of patients receiving hemodialysis in an Iranian healthcare setting, an aspect that has not been extensively explored before.MethodsA parallel-controlled clinical trial was conducted involving 60 caregivers, divided into intervention and control groups. The intervention group participated in an 8-session peer support program tailored to their identified needs, including coping with stress, social isolation, and financial challenges. The Zarit Care Burden Interview Scale was used to measure care burden before and after the intervention.ResultsThe study revealed statistically significant reductions in care burden, particularly in physical, social, and emotional dimensions, among caregivers in the intervention group compared to the control group. The total care burden score showed a marked decrease, indicating the effectiveness of the peer support intervention. While economic challenges remained a concern, the intervention had a limited impact in this domain.ConclusionThis study demonstrates that peer support groups significantly alleviate the care burden experienced by caregivers of patients receiving hemodialysis, improving their well-being across several dimensions. The findings highlight the importance of integrating peer support strategies into healthcare programs for chronic disease management and underscore the need for supplementary economic support measures to comprehensively address caregivers’ needs. Future research should explore the scalability and long-term sustainability of such interventions and address the unique economic challenges faced by these caregivers.Trial registrationThis study was registered in the Iranian Registry of Clinical Trials (IRCT) under the registration number IRCT20220724055540N1 on 11/08/2022.

Tuberculosis in infertility and in vitro fertilization-embryo transfer.

Tuberculosis (TB) is a prominent infectious disease globally that imposes a substantial health burden. Genital TB (GTB), an extrapulmonary manifestation, leads to complications such as tubal adhesions, blockage, and diminished ovarian function, culminating in infertility, and is recognized as a prevalent cause of infertility in nations with high-burden TB. In regions with low TB rates, infertility and active TB during pregnancy have been reported to be most common among female immigrants from countries with high-burden TB. In the context of TB, pregnant women often exhibit exacerbated symptoms after in vitro fertilization-embryo transfer (IVF-ET), heightening the risk of dissemination. Miliary pulmonary TB and tuberculous meningitis pose a serious threat to maternal and fetal health. This article integrates recent epidemiological data and clinical research findings, delineating the impact of TB on infertility and assisted reproduction and particularly focusing on the diagnosis and treatment of GTB, underscored by the imperative of TB screening before IVF-ET. Our objective is to increase awareness among respiratory and reproductive health professionals, promoting multidisciplinary management to enhance clinical vigilance. This approach seeks to provide patients with judicious reproductive plans and scientifically rigorous pregnancy management, thereby mitigating adverse pregnancy outcomes related to TB activity.

Predictors of symptom recurrence and survival in patients with malignant gastric outlet obstruction treated with self-expanding metal stents.

Malignant gastric outlet obstruction (GOO) poses a substantial symptomatic burden. While various therapeutic options exist, self-expanding metal stents (SEMS) are a common palliative choice for patients who are ineligible for surgery. We studied SEMS outcomes to identify factors influencing stent dysfunction and patient survival. A multi-centre, retrospective review of 190 patients with GOO undergoing SEMS at three tertiary hospitals was performed over 2016-2022. Technical success, clinical success and adverse outcomes were recorded. Predictors of stent dysfunction and survival were evaluated using multivariate regression. Technical success was achieved in 186/190 (97.9%) and clinical success in 156/186 (83.9%), defined as post-procedural gastric outlet obstruction symptom score (GOOSS) ≥2. Eighty-two (44.1%) patients experienced an adverse event with stent occlusion the most common (23.1%). Approximately one-third (32.3%) underwent a repeat intervention. Mean stent patency time was 67 days (standard deviation=76), and median post-stent survival was 95 days (37-197). Covered and partially covered SEMS carried three times the risk of stent dysfunction compared to uncovered SEMS (odds ratio 3.06, p=0.008). Mortality predictors were Eastern Cooperative Oncology Group score ≥2 (p=0.03), extrinsic outlet obstruction (p=0.05) and presence of ascites (p=<0.001). SEMS demonstrated technical and clinical success but posed a high risk of recurrence, with stent patency time falling short of survival in our cohort. With an evolving landscape of therapeutics for GOO, appropriate patient selection is paramount. Individuals with reduced performance status, extrinsic obstruction and/or ascites may be better candidates for SEMS due to more limited life expectancy. In this setting, uncovered SEMS carry the lowest risk of reintervention.

Frontiers of myopia research in the 21st century: A bibliometric analysis of the top 100 most influential articles in the field.

Myopia is the most common refractive error worldwide, contributing not only to visual impairment but also serving as a potential risk factor for various severe ocular diseases. Its impact on patients' quality of life and health is significant and imposes substantial socioeconomic burdens. In this study, we analyzed the top 100 most cited articles related to myopia published in the Web of Science Core Collection database from January 2000 to February 2024. Using data visualization tools CiteSpace, VOSviewer, and Scimago Graphica, we identified the most influential research papers and academic journals in the field of myopia. The top 100 most influential articles were published in 25 renowned journals across 30 countries, with Investigative Ophthalmology & Visual Science being the most prolific. Ophthalmology had the highest total citation frequency, while The Lancet had the highest average citation frequency. The United States and the National University of Singapore were the top countries and institutions with the most published papers. The 3 major research directions are Ophthalmology, Medicine, General & Internal, and Genetics & Heredity. The top 5 co-occurring keywords were refractive error, risk factors, prevalence, eye growth, and form-deprivation myopia. Cluster analysis results highlighted focal points such as retinal detachment, high myopia, and contrast sensitivity, indicating potential future research trends. Prospective research directions include investigating the pathogenesis of myopia, updating diagnostic technologies, and identifying risk genes for myopia and its complications.

Assessing the factors associated with body image perception and quality of life of Palestinian women undergoing breast cancer treatment: a cross-sectional study

BackgroundWorldwide, breast cancer has replaced lung cancer and has become the most commonly diagnosed malignancy. Breast cancer poses a significant burden on the health and quality of life of women and can lead to substantial physical burdens and significant psychological problems, including distress, anxiety, depression, and sexuality-related issues, including negative body image. This study was conducted to assess how women diagnosed with, treated, and/or receiving treatment for breast cancer perceived their body image.MethodsA cross-sectional study design was used to assess body image perceptions among Palestinian women diagnosed with breast cancer. The study was conducted in four different hospitals located in the West Bank of Palestine where women with breast cancer received their treatments or visited for follow-up care in the period between November 2023 and March 2024. An interviewer-administered questionnaire was used to collect the data. Body perception was assessed using the body image self-rating questionnaire for breast cancer (BISQ-BC).ResultsIn this study, 376 women with breast cancer completed the interviewer-administered questionnaire (response rate = 75.2%. The mean age of the women was 44.0 ± 5.3 years. Of the women, 74.7% agreed or strongly agreed that they cared about their body image. On the other hand, 43.1% of the women were not satisfied with their body image and 58.8% did not think that their body image was attractive. Multiple linear regression showed that younger age, employment status, living in cities, marital status, educational level, presence of comorbidities, and longer time passes since diagnosis with breast cancer were associated with the different aspects of body image perception and behavior.ConclusionThe findings of this study indicated that Palestinian women with breast cancer were concerned about their body image. The findings also indicated that breast cancer and its treatment posed a significant burden on the physical and psychosocial well-being of the affected women and impacted the different dimensions of their lives, including their perceptions of their body image. Patients with significant physical and body image changes might benefit from reconstructive surgeries, psychosocial support, cognitive behavioral therapy, and nutritional, and physical activity interventions.

Fate and mass budget of microplastic in the Beibu Gulf, the northern South China sea

This study investigated the distribution, abundance, and mass budget of microplastics (MPs) in the Beibu Gulf, Northern South China Sea, focusing on their ecological significance and anthropogenic influence. Microplastics were found in all water and sediment samples, with concentrations in surface water ranging from 0.10 to 0.89 items/m³, and in bottom water from 0 to 0.85 items/m³. Sediment samples exhibited higher levels, ranging from 13.12 to 155.59 items/kg. The spatial distribution revealed higher concentrations along the northern Gulf and Guangxi Province, suggesting significant human influence from coastal activities, such as mariculture and industrial discharges. The study utilized both field data and a mass balance box model to estimate the MPs mass budget, revealing that oceanic flow and riverine discharge are major contributors, accounting for 49% and 52% of MPs, while Atmospheric deposition and sedimentation represents 8% and 1%, respectively. The inventory estimation calculated that 0.24 tons of MPs exist in the water column, and 137 tons in the sediment, emphasizing the substantial environmental burden posed by these pollutants. The significance of this research lies in its comprehensive assessment of MPs in a semi-enclosed gulf, providing critical insight into the role of coastal and hydrodynamic processes in MP distribution. This study highlights the urgent need for better waste management practices in coastal regions to mitigate microplastic pollution and its detrimental effects on marine ecosystems.

Discovery and analysis of the relationship between organic components in exhaled breath and bronchiectasis

The prevalence of patients with bronchiectasis (BE) has been rising in recent years, which increases the substantial burden on the family and society. Exploring a convenient, effective, and low-cost screening tool for the diagnosis of BE is urgent. We expect to identify the accuracy (ACC) of breath biomarkers (BBs) for the diagnosis of BE through breathomics testing and explore the association between BBs and clinical features of BE. Exhaled breath samples were collected and detected by high-pressure photon ionization time-of-flight mass spectrometry in a cross-sectional study. Exhaled breath samples were from 215 patients with BE and 295 control individuals. The potential BBs were selected via the machine learning (ML) method. The overall performance was assessed for the BBs-based BE detection model. The significant BBs between different subgroups such as the severity of BE, acute or stable stage, combined with hemoptysis or not, with or without nontuberculous mycobacterium (NTM),P. aeruginosa(P.a) isolation or not, and the BBs related to the number of involved lung lobes and lung function were discovered and analyzed. The top ten BBs based ML model achieved an area under the curve of 0.940, sensitivity of 90.7%, specificity of 85%, and ACC of 87.4% in BE diagnosis. Except for the top ten BBs, other BBs were found also related to the severity, acute/stable status, hemoptysis or not, NTM infection,P.aisolation, the number of involved lobes, and three lung functional parameters in BE patients. BBs-based BE detection model showed good ACC for diagnosis. BBs have a close relationship with the clinical features of BE. The breath test method may provide a new strategy for BE screening and personalized management.

Role and mechanism of KIAA1429 in regulating cellular ferroptosis and radioresistance in colorectal cancer.

Colorectal cancer (CRC) is one of the most common non-cutaneous malignancies, causing significant mortality and a substantial burden. This study aims to explore the role of KIAA1429 (also known as vir-like m6A methyltransferase associated [VIRMA]) protein in the radioresistance of CRC. CRC cells and a radioresistant cell line were cultured, and KIAA1429 expression was detected. After the down-regulation of KIAA1429, its effect on the radioresistance and ferroptosis of cancer cells was analyzed. The role of ferroptosis in radioresistance was verified. The binding relationship among long non-coding RNA endogenous Bornavirus-like nucleoprotein 3, pseudogene (lncRNA EBLN3P), microRNA (miR)-153-3p, and KIAA1429 was analyzed. KIAA1429 and lncRNA EBLN3P were highly expressed in CRC, while miR-153-3p was poorly expressed. KIAA1429 and lncRNA EBLN3P were further increased/decreased in the radioresistant cells. KIAA1429 knockdown decreased the survival rate of the radioresistant cell line after X-ray irradiation and increased gamma H2A histone family member X (γ-H2AX), ferroptosis, and oxidative stress. A ferroptosis inhibitor alleviated the inhibitory effect of KIAA1429 knockdown on radioresistance. KIAA1429-mediated m6A modification up-regulated lncRNA EBLN3P, and lncRNA EBLN3P increased KIAA1429 by competitively binding to miR-153-3p. miR-153-3p silencing or lncRNA EBLN3P overexpression attenuated the promotion of ferroptosis and the inhibition of radioresistance induced by KIAA1429 knockdown. Overall, KIAA1429-mediated m6A modification up-regulated lncRNA EBLN3P expression, and lncRNA EBLN3P increased KIAA1429 expression by competitively binding to miR-153-3p, thus reducing ferroptosis and increasing the radioresistance of CRC.

Neuroimaging-Based Brain Morphometry in Alzheimer’s Disease

Background/Objectives: Alzheimer’s disease (AD) is a leading cause of death worldwide, affecting millions of older Americans and resulting in a substantial economic burden. The Alzheimer’s Disease Neuroimaging Initiative (ADNI) aims to investigate and develop treatments for AD. Methods: This study included 60 participants, divided equally into AD and control cohorts, and utilized magnetic resonance imaging (MRI) scans to detect gray matter volumetric alterations, a key biomarker of AD. The participants’ cortical volume and surface area were quantified using an automated pipeline in MIMICS (Materialise Interactive Medical Imaging Control System). Results: A multivariate regression analysis was conducted to explore the relationship between cortical measurements and potential factors influencing AD susceptibility. The study found that both cortical volume and surface area were statistically significant predictors of AD (p = 0.0004 and p = 0.011, respectively). Age was also a significant factor, with the 65–70 age group showing the strongest association (p &lt; 0.001). The model achieved an accuracy of 0.68 in predicting AD. Conclusions: While voxel-based morphometry (VBM) using MIMICS showed promise, further development of the automated pipeline could enhance accuracy and correlation indices. These findings contribute to our understanding of brain atrophy in AD pathophysiology and highlight the potential of MRI morphometry as a tool for AD biomarker development.

Population-Level Distribution, Risk Factors, and Burden of Mortality and Disability-Adjusted Life Years Attributable to Major Noncommunicable Diseases in Western Europe (1990-2021): Ecological Analysis.

Cardiovascular diseases (CVDs) and neoplasms are leading causes of mortality worldwide. This study aims to provide a comprehensive analysis of the mortality burden and disability-adjusted life years (DALYs) attributable to CVDs and neoplasms in Western Europe, investigate associated risk factors, and identify regional disparities. Additionally, the study evaluates the effectiveness of the Action Plan for the Prevention and Control of Non-Communicable Diseases (NCDs) in promoting healthier lives in the region. The study collected data on mortality and DALYs due to CVDs and cancers from 24 Western European countries using the Global Burden of Disease Study 2021. The analysis explored age, sex, and country-specific patterns, as well as risk factors contributing to these deaths. Additionally, the study examined time trends by calculating the annual percent change in mortality rates from 1990 to 2021 by region and cause. In 2021, CVDs and neoplasms accounted for 27.8% and 27.1% of total deaths in Western Europe, with age-standardized death rates of 106.8 and 125.8 per 100,000, respectively. The top two CVDs in this region were ischemic heart disease and stroke, with age-standardized death rates of 47.27 (95% uncertainty interval [UI] 50.42-41.45) and 27.06 (95% UI 29.17-23.00), respectively. Similarly, the top two neoplasms were lung cancer and colorectal cancer, with age-standardized death rates of 26.4 (95% UI 27.69-24.47) and 15.1 (95% UI 16.25-13.53), respectively. Between 1990 and 2021, CVD mortality rates decreased by 61.9%, while cancer rates decreased by 28.27%. Finland had the highest CVD burden (39.5%), and Monaco had the highest rate of cancer-related deaths (34.8%). Gender differences were observed, with males experiencing a higher burden of both CVDs and cancer. Older individuals were also more at risk. Smoking had a stronger impact on CVD mortality and DALYs in males, while a higher Human Development Index was associated with increased cancer deaths and DALYs in females. The study findings highlight the substantial burden of NCDs, particularly CVDs and cancer, in Western Europe. This underscores the critical need for targeted interventions and effective implementation of the Action Plan for the Prevention and Control of NCDs to achieve the goal of ensuring healthy lives for all.

Household air pollution and respiratory health in Africa: persistent risk and unchanged health burdens.

Despite evidence emerging from the Global Burden of Disease studies that biomass use and household air pollution are declining globally, with important positive health impacts for households in low- and middle-income countries, these trends have not been equally documented in African countries. This review describes the state of household air pollution exposure and its relationship with respiratory disease in Africa. African studies on this topic are limited, and generally focus on respiratory infections. Most evidence emerge from models based on the Global Burden of Disease data, and from limited individual epidemiological studies across the continent. More than 80% of the African population is exposed to household air pollution. Women and children continue to bear the substantial burden of exposure. Evidence from limited exposure-response studies strongly points to household air pollution being the major driver of acute and chronic respiratory diseases on the continent. Respiratory infections, particularly in children, and other chronic respiratory diseases, are strongly attributable to household air pollution. Elimination of such exposures through interventions such as cleaner fuels and preferably, electricity, is critical to improving respiratory health on the continent.

Seropositivity of hepatitis A and E viruses in patients attending a tertiary care center in central India

Objectives: Hepatitis A virus (HAV) and hepatitis E virus (HEV) infections are significant global health concerns that contribute to acute viral hepatitis. This study aimed to investigate the prevalence of HAV, HEV, and co-infections in a tertiary care hospital setting in central India. Materials and Methods: This retrospective observational study analyzed 987 clinical specimens collected from suspected acute viral hepatitis cases over 5 years (2019–2023). Commercially available enzyme-linked immunosorbent assay kits were used to detect HAV and HEV immunoglobulin M antibodies. Statistical analysis: Demographic data and clinical information were collected and analyzed using Chi-square tests. P &lt; 0.05 was considered statistically significant, indicating a significant association between the variables under investigation. Results: Overall, 32.72% of patients were seropositive for either HAV, HEV, or both. The prevalence of HAV was 22.9%, HEV was 9.83%, and co-infection was 3.24%. HAV infection was more prevalent in children (0–14 years), whereas HEV was more prevalent in adults. Both HAV and HEV infections were associated with elevated liver function markers, with the highest levels observed in co-infected cases. The monsoon season had the highest number of cases. Conclusions: This study revealed a substantial burden of HAV, HEV, and co-infections in central India. The observed sex—and age-specific prevalence patterns warrant further investigation. Effective public health strategies addressing sanitation, hygiene practices, and HAV vaccination programs are crucial to reducing the disease burden.

Prediction of Cardiac ATTR Depletion by NI006 (ALXN2220) Using Mechanistic PK/PD Modeling.

NI006 (aka ALXN2220) is a therapeutic antibody candidate in phase III clinical development for the depletion of amyloid transthyretin (ATTR) in patients with ATTR cardiomyopathy, an infiltrative cardiomyopathy leading to increased left ventricular wall thickness (LVWT). The mode-of-action consists in removal of disease-causing amyloid accumulations by activating phagocytic immune cells, a mechanism without precedent in cardiology. To select a safe and potentially efficacious dose range and treatment duration for a combined first-in-human and proof-of-concept clinical phase Ib study, we developed a mechanistic pharmacokinetic and pharmacodynamic (PK/PD) model that can predict NI006 exposure, its effects on cardiac amyloid load and on LWVT, which is a predictor of heart failure in this disease. The PK/PD model predictions supported 0.3 mg/kg monthly dosing as a safe starting dose and identified 10-60 mg/kg monthly as the potentially efficacious dose range with substantial and dose dependent cardiac amyloid burden reduction within 4 months for 60 mg/kg and 10 months for 10 mg/kg. These predictions were in good agreement with the observed primary results of the clinical phase Ib study where amyloid burden was measured by imaging. This novel translational PK/PD model provided important predictions to guide the design of the phase Ib study of NI006, indicating the value of this approach to integrate preclinical results into clinical trial design and increase translational success.