Economic Burden Research Articles

Deciphering Immune-related Gene Signatures in Diabetic Retinopathy: Insights from In silico Analysis and In vitro Experiment.

Diabetes retinopathy (DR) is one of the most common microvascular consequences of diabetes, and the economic burden is increasing. Our aim is to decipher the relevant mechanisms of immune-related gene features in DR and explore biomarkers targeting DR. Provide a basis for the treatment and prevention of DR. The immune infiltration enrichment score of DR patients was evaluated from the single- cell RNA sequencing dataset, and the samples were divided into low immune subgroups and high immune subgroups based on this result. Through weighted gene correlation network analysis, differentially expressed genes (DEGs) between two subgroups were identified and crossed with genes with the strongest immune association, resulting in significant key genes. Then divide the DR individuals into two immune related differentially expressed gene (IDEG) clusters, A and B. Submit cross DEGs between two clusters through Gene Set Enrichment Analysis (GSEA) to further explore their functions. A protein-protein interaction (PPI) network of IDEG was established to further identify central genes associated with DR. Use the discovered central genes to predict the regulatory network involved in the pathogenesis of DR. Then, the role of the identified hub gene in the pathogenesis of DR was further studied through in vitro experiments. We found that the immune scores of DR and control groups were different, and 27 IDEGs were found in the DR subgroup. Compared with cluster A, the proportion of cytotoxic lymphocytes, B lineage, monocyte lineage, and fibroblasts in DR patients in cluster B is significantly enriched. GSEA indicates that these genes are associated with T cell activation, regulation of immune response processes, lymphocyte-mediated immunity, TNF signaling pathway, and other signaling pathways. The PPI network subsequently identified 10 hub genes in DR, including SIGLEC10, RGS10, PENK, FGD2, LILRA6, CIITA, EGR2, SIGLEC7, LILRB1, and CD300LB. The upstream regulatory network and lncRNA miRNA mRNA ceRNA network of these hub genes were ultimately constructed. The discovery and identification of these genes will provide biomarkers for targeted prediction and treatment of DR. By integrating bioinformatics analysis and in vitro experiments, we have identified a set of central genes, indicating that these genes can serve as potential biomarkers for DR, which may be promising targets for future DR immunotherapy interventions.

Effect of heatwaves on mortality of Alzheimer's disease and other dementias among elderly aged 60 years and above in China, 2013–2020: a population-based study

BackgroundChina has the largest number of dementia patients in the world, posing a significant health and economic burden. Alzheimer's disease (AD) and other dementia patients face a higher risk of mortality during heatwaves, but relevant studies on this topic have been limited so far. MethodsThe study extracted data from the China Cause of Death Reporting System (CDRS) on deaths of AD and other dementia patients aged 60 years and above between 2013-2020. Using an individual-level, time-stratified, and case-crossover study design, the effects of heatwaves across nine scenarios on dementia mortality were quantified by conditional logistic regression combined with distributed lag non-linear model (DLNM). Additionally, the attributable fractions (AFs) of deaths due to heatwaves were calculated. FindingsA total of 399,036 death cases were reported caused by AD and other dementias during the study period. It was found that heatwaves significantly increased the risk of death among people with AD and other dementias. As the intensities and durations of the heatwaves increased, the lag0-7 cumulative odds ratios (CORs) of mortality increased progressively from 1·140 (95% CI: 1·118, 1·163) under the mildest heatwave to 1·459 (95% CI: 1·403, 1·518) under the most severe one, across nine heatwave scenarios examined. Additionally, under specific heatwave scenarios, sex and regions modified the mortality risk, but no significant age differences were observed. The AFs of AD and other dementia mortality due to milder heatwaves were lower compared to more severe heatwaves, ranging from 12·281% (95% CI: 10·555%, 14·015%) to 31·460% (95% CI: 28·724%, 34·124%). InterpretationThe study provided critical insights into the substantial increase in heatwave-related mortality among AD and other dementia patients during and after heatwave events. The results from our quantitative analyses will provide needed scientific evidence for policymakers and practitioners to develop relevant policies and guidelines to protect the health and well-beings of vulnerable populations in future in the context of both seasonal changes and long-term climate change. FundingThis work was supported by the Project of Prevention and Intervention on Major Diseases for Elderly in China, NCNCD [00240201307], the National Key Research and Development Program of China [2022YFC2602301, 2023YFC2308703] and the Science and Technology Fundamental Resources Investigation Program of China [2017FY101201].

Isoliquiritigenin alleviates SLC7A11-mediated efferocytosis inhibition to promote wounds healing in diabetes

The healing process of chronic wounds often progresses slowly and is fraught with challenges, imposing increasing economic burdens and physical suffering on patients. Managing persistent wound inflammation and stimulating angiogenesis are crucial elements in promoting wound healing. Plants have been playing a key role in traditional medicine, and their abundant bioactive components continually inspire the development and innovation of new drugs. Isoliquiritigenin (ISL), a flavonoid compound derived from licorice roots known as chalcone, has demonstrated multifaceted pharmacological potential. However, its effects on diabetic wounds and the detailed mechanisms remain to be investigated. Through in-depth exploration using network pharmacology, we successfully predicted potential therapeutic targets of ISL for ischemic diseases. The revealed mechanisms primarily focused on the critical pathway of efferocytosis. Subsequent in vivo experiments demonstrated that ISL significantly enhanced the efferocytosis of dendritic cells (DC), improving the functional behaviors of endothelial cells. Further research indicated that ISL promoted DC efferocytosis by regulating SLC7A11-mediated glycolysis. Notably, the overexpression of SLC7A11 diminished the positive effects of ISL, suggesting a potential antagonistic role of SLC7A11 in the regulatory process. In the wounds of diabetic mice, we observed that ISL accelerated DC efferocytosis and angiogenesis, resulting in faster wound closure and better tissue repair. In summary, this study not only demonstrates the broad potential of ISL in managing diabetic wounds but also delves deeply into its mechanisms, laying a solid theoretical foundation for future clinical applications.

Advanced Therapeutic Medicinal Products in Bone and Cartilage Defects.

The number of patients with functional loss of bone and cartilage tissue has shown an increasing trend. Insufficient or inappropriate conventional treatments applied for trauma, orthopedic diseases, or other bone and cartilage-related disorders can lead to bone and cartilage damage. This represents a worldwide public health issue and a significant economic burden. Advanced therapeutic medicinal products (ATMPs) proposed promising alternative therapeutic modalities by application of cell-based and tissue engineering approaches. Recently, several ATMPs have been developed to promote bone and cartilage tissue regeneration. Fifteen ATMPs, two related to bone and 13 related to cartilage, have received regulatory approval and marketing authorization. However, four ATMPs were withdrawn from the market for various reasons. However, ATMPs that are still on the market have demonstrated positive results, their broad application faced limitations. The development and standardization of methodologies will be a major challenge in the coming decades. Currently, the number of ATMPs in clinical trials using mesenchymal stromal cells or chondrocytes indicates a growing recognition that current ATMPs can be improved. Research on bone and cartilage tissue regeneration continues to expand. Cell-based therapies are likely to be clinically supported by the new ATMPs, innovative fabrication processes, and enhanced surgical approaches. In this study, we highlighted the available ATMPs that have been used in bone and cartilage defects and discussed their advantages and disadvantages in clinical applications.

Economic burden of cervical cancer in Latin America: A real-world study

Economic burden of cervical cancer in Latin America: A real-world study

Transforming steatotic liver disease management: The emerging role of GLP-1 receptor agonists.

Chronic liver disease is a major cause of mortality, with approximately 2 million deaths worldwide each year, and it poses a significant economic burden. The most common cause of chronic liver disease in the United States and Europe is steatotic liver disease (SLD), which includes metabolic dysfunction-associated SLD, metabolic dysfunction and alcohol-associated SLD, and alcohol-associated liver disease (ALD). Effective treatment of these conditions is essential to reduce the liver disease burden, with promising approaches including treating cardiometabolic risk factors and excessive alcohol intake. Glucagon-like peptide 1 receptor agonists, both as monotherapy and in combination with other drugs, are gaining attention for their beneficial impact on cardiometabolic risk factors and excessive alcohol intake. In this review, we examine the molecular and clinical effects of glucagon-like peptide 1 receptor agonists, focusing on their direct hepatic steatohepatitis and liver fibrosis but also the indirect influence on cardiometabolic risk factors and excessive alcohol intake as key features of SLD. We also explore the future implications of glucagon-like peptide 1 receptor agonists for treating metabolic dysfunction-associated SLD, metabolic dysfunction and alcohol-associated SLD, alcohol-associated liver disease, and the potential challenges.

Designing persuasive communication models for vaccine acceptance in isolated communities: A mass communication approach

This study introduces the Persuasive Communication Model as a novel approach to address vaccine hesitancy in isolated U.S. communities, where infectious diseases such as measles and influenza continue to pose significant public health threats. By integrating mass communication theories like the Elaboration Likelihood Model (ELM) and Social Cognitive Theory (SCT), with AI-driven message personalization, the model effectively tailors health communication strategies to the cultural, cognitive, and socio-economic contexts of vaccine-hesitant populations. In a randomized controlled trial, the model increased vaccination uptake by over 20% compared to traditional methods, while also enhancing trust in healthcare systems. The model’s adaptive communication, utilizing both digital platforms and community leaders, was instrumental in overcoming barriers related to geographic isolation, religious beliefs, and cultural resistance. These findings are particularly relevant for enhancing national public health security and reducing the economic burden of vaccine-preventable diseases. The study highlights the model's superiority over static communication frameworks, offering scalable applications for broader public health interventions.

Developing a battery of physical performance tests to predict functional disability in Japanese older adults: A longitudinal study from the Kasama study.

Preventing functional disability benefits the quality of life of older adults and mitigates the economic burden of an aging society. However, the most effective physical performance tests and optimal cut points for identifying older adults at risk of functional disability remain unclear, and Japan lacks physical function-based assessment tools. We aimed to identify the physical performance tests related to functional disability and to develop a predictive test battery for it. We included 975 older adults (mean 72.8 ± 5.2 years, 55.4% women) in Kasama City, Japan. Functional disability was defined as certification of care level 2 or above based on the long-term care insurance system. Cox proportional hazards analysis examined the association between physical performance tests and incident functional disability. During a mean follow-up of 8.6 years (maximum 14 years), 236 participants (24.2%) developed functional disability. After adjusting for covariates, higher performances in grip strength, single-leg balance with eyes open (SLB), timed up-and-go (TUG), five-repetition sit-to-stand (5-STS), and 5-m habitual walk were significantly associated with a lower risk of functional disability. In a stepwise model, SLB, TUG, and 5-STS were key predictors of functional disability. Receiver operating characteristic analysis determined optimal cut points of 32.6/32.7 s for SLB, 6.5/6.6 s for TUG, and 7.8/7.9 s for 5-STS. We developed a predictive battery combining these cut points (area under the curve = 0.78). The developed battery of physical performance tests predicts future functional disability and is useful for screening older adults at high risk. Geriatr Gerontol Int 2024; ••: ••-••.

Machine learning approaches toward an understanding of acute kidney injury: current trends and future directions.

Acute kidney injury (AKI) is a significant health challenge associated with adverse patient outcomes and substantial economic burdens. Many authors have sought to prevent and predict AKI. Here, we comprehensively review recent advances in the use of artificial intelligence (AI) to predict AKI, and the associated challenges. Although AI may detect AKI early and predict prognosis, integration of AI-based systems into clinical practice remains challenging. It is difficult to identify AKI patients using retrospective data; information preprocessing and the limitations of existing models pose problems. It is essential to embrace standardized labeling criteria and to form international multi-institutional collaborations that foster high-quality data collection. Additionally, existing constraints on the deployment of evolving AI technologies in real-world healthcare settings and enhancement of the reliabilities of AI outputs are crucial. Such efforts will improve the clinical applicability, performance, and reliability of AKI Clinical Support Systems, ultimately enhancing patient prognoses.

Mental health and well-being in prisons and places of detention.

This study aims to address the critical mental health challenges faced by individuals in prisons and places of detention. By introducing and validating a novel conceptual framework that integrates social determinants of health with the stress process model, this study aims to provide actionable insights for improving mental health care in correctional settings. The research seeks to inform policymakers, prison administrators and mental health professionals about effective interventions and systemic reforms that can reduce recidivism, enhance rehabilitation and promote a more humane and just criminal justice system. This study uses a multi-method research design integrating a systematic literature review, qualitative interviews, multi-criteria evaluation (MCE) and a small-scale empirical study within a correctional facility. The systematic review follows PRISMA guidelines, analysing peer-reviewed articles, government reports and policy documents. Semi-structured interviews with 25 mental health professionals provide practical insights, whereas the MCE assesses intervention effectiveness based on expert consensus. The empirical study involves baseline assessments, intervention implementation and follow-up evaluations using validated tools, providing robust data to validate the proposed conceptual framework that integrates social determinants of health with the stress process model. This study finds that mental health disorders are significantly more prevalent in prison populations than in the general population, with interventions like cognitive behavioural therapy (CBT), peer support programs and trauma-informed care showing considerable effectiveness in reducing symptoms. Emerging technologies such as AI and telemedicine present promising avenues for enhancing care but require careful ethical consideration. The research also highlights the critical role of social determinants and the importance of systemic reforms, such as reducing solitary confinement and integrating prison health care with broader public health systems, in improving inmate mental health and reducing recidivism. This study's quasi-experimental design, while robust, may limit the generalizability of the findings to other correctional settings because of specific facility characteristics. Additionally, the sample size for qualitative interviews, although diverse, could have been larger to provide more nuanced insights, particularly for underrepresented groups. This study highlights the need for more longitudinal research to assess the long-term effects of interventions and the scalability of approaches across different cultural and legal contexts. Future studies should address these limitations by using more diverse sampling, larger sample sizes and extended follow-up periods. This study provides actionable insights for policymakers and prison administrators, emphasizing the need to integrate evidence-based mental health interventions, such as CBT and trauma-informed care, into prison reform strategies. It highlights the importance of training correctional staff in mental health first aid and the potential of emerging technologies like AI and telemedicine to enhance care delivery in resource-limited settings. Implementing these recommendations could significantly improve inmate mental health outcomes, reduce recidivism rates and promote a more humane and effective correctional system, with broader benefits for public health and social equity. Improving mental health care in prisons has significant social implications, particularly in promoting social justice and reducing inequalities. Effective mental health interventions can help break the cycle of incarceration and recidivism, particularly in marginalized communities disproportionately affected by the criminal justice system. By addressing the mental health needs of incarcerated individuals, society can foster safer communities, reduce crime rates and alleviate the economic burden on the criminal justice and health-care systems. Furthermore, enhancing mental health care in prisons reflects a commitment to human dignity, fairness and the rehabilitation of offenders, contributing to a more just and compassionate society. This study introduces a novel conceptual framework that integrates social determinants of health with the stress process model, specifically tailored for correctional facilities. It provides original empirical data from a real-world prison setting, offering new insights into the effectiveness of mental health interventions, such as CBT and trauma-informed care. The study's value lies in its comprehensive approach, combining quantitative and qualitative methods, and its focus on underrepresented populations in correctional settings. By addressing significant gaps in the literature, this research offers practical recommendations for policymakers and practitioners, contributing to improved mental health outcomes and reduced recidivism.

Sleep Health Patterns in Romania: Insights from a Nationwide Cross-Sectional Online Survey

Background: Sleep is one of the most essential processes for sustaining cognitive, emotional, and physical health across all age groups. Insomnia or inadequate sleep significantly impacts health and poses economic burdens due to increased healthcare costs and reduced productivity. Objectives and Methods: This study aimed to investigate sleep quality in the Romanian active population using an online survey incorporating the Pittsburgh Sleep Quality Index (PSQI). Conducted over four months in 2023, the survey gathered 2243 complete responses from urban and rural residents over the age of 18. Results: The results highlight gender and urban–rural disparities in sleep quality, revealing that females and urban residents experienced poorer sleep compared to their counterparts. Additionally, sleep quality was found to significantly worsen with age, with elders (56+ years) reporting the highest PSQI scores, indicating greater sleep difficulties compared to middle-aged adults and youngsters. A high prevalence of sleep disturbances, daytime dysfunctions, and sleep medication use was reported. Common pre-sleep activities included using electronic devices and watching TV, while fewer participants engaged in reading books or consuming alcohol and caffeine. Additionally, participants’ bedding preferences were documented. Conclusions: Our study highlights the influence of various factors on sleep quality and emphasizes the need for targeted public health interventions to improve sleep health in Romania.

Life After Invasive Meningococcal Disease: Insights from Survivors and Their Caregivers.

Invasive meningococcal disease (IMD) has a low incidence but is a life-threatening illness that is preventable via vaccination. Even with treatment, up to 10-15% of cases are fatal, and many survivors may experience severe long-term sequelae. Building upon the acute-phase findings presented in the Part1 manuscript for this study, we describe the long-term physical, social, psychological, and economic burden of IMD on US survivors and their caregivers in this Part2 manuscript. This was a novel, non-interventional, mixed-methods study among US survivors and their caregivers using a bespoke survey and qualitative interviews. Ten adult survivors, one adolescent survivor, and three caregivers participated in this study. Survivors described extensive physical, neurological, and systemic sequelae, including difficulty walking (11/11), repeat secondary infections (9/11), and numbness (6/11), among others, which were echoed by caregivers. Survivors shared that IMD had negatively impacted their long-term quality of life, citing long-term impacts including emotional impacts (11/11), social impacts (10/11), memory (7/11) and attention (5/11) problems, and difficulty with functional (10/11), self-care (7/11), and physical (6/11) activities. Caregivers were also impacted, describing emotional trauma (3/3), sleep problems (2/3), and day-to-day challenges (2/3). Long-term financial challenges related to healthcare resource utilization were substantial, with specialized care and rehabilitation therapy expenses (11/11), insurance challenges (8/11), and high out-of-pocket costs (6/11) for survivors. Productivity losses were also commonly described by survivors (9/11); sequelae hindered ability to attend school (9/11) or work full time (8/11). Caregivers (2/3) described taking leave from their employment, affecting family income. The humanistic burden of IMD on survivors and their caregivers is substantial and persistent. A comprehensive approach, including preventative measures (e.g., vaccination) and long-term medical, psychological, and financial support for those affected, is needed to mitigate the burden of IMD. A video abstract is available with this article. Video abstract (MP4 1,17,430kb).

Initial Experiences with Invasive Meningococcal Disease: Insights from Survivors and Their Caregivers.

Invasive meningococcal disease (IMD) has a low incidence but is a life-threatening illness with a 10-15% mortality rate. Even with timely treatment, survivors may experience acute and long-term health complications. While meningococcal vaccines are recommended for adolescents and young adults in the USA, vaccination coverage remains uneven across serotypes. This study investigated the physical, social, psychological, and economic burden of IMD on survivors and their caregivers in the USA during the acute phase (Part1, presented in this manuscript) and the long-term phase (Part2, presented in a separate manuscript) of IMD. This study implemented a non-interventional, mixed-methods approach using a bespoke survey and qualitative interviews (designed on the basis of a preliminary conceptual model of IMD) with US survivors and their caregivers. A total of 11 survivors (1 adolescent, 10 adults) and 3 caregivers participated in the study. Survivors contracted IMD during infancy (n = 2), childhood (n = 3), or adulthood (n = 6), and often described leading healthy lives pre-IMD. At IMD onset, interactions with the healthcare system impacted participants' experiences; confusion and care delays were common, and procedures were often invasive (e.g., amputations). Survivors commonly experienced symptoms including skin rash (7/11), fever (6/11), and unconsciousness (6/11), consistent with caregivers' reports. Survivors able to report on the short-term impacts of IMD (n = 9) described functional limitations (9/9), emotional impacts (6/9) such as fear and trauma, and school (6/9), work (4/9), and financial (5/9) challenges. Caregivers also experienced emotional impacts (3/3) and family (2/3), work (3/3), and financial (3/3) impacts during the acute phase. IMD places a significant humanistic burden on survivors and their caregivers during the acute phase. Results from Part1 of this study indicate a need for increased disease awareness and healthcare provider education, expeditious diagnosis, and improved access to prevention methods such as available meningococcal vaccines. A video abstract is available with this article. Video abstract (MP4 1,24,432kb).

The economic and social burden of congenital thrombotic thrombocytopenic purpura (cTTP) in Italy

Background: Congenital thrombotic thrombocytopenic purpura (cTTP) is a rare genetic disorder characterized by an abnormal clotting process leading to serious health complications such as thrombocytopenia and hemolytic anemia. Despite its clinical significance, the estimated broader economic and social impacts in Italy on patients and society remain underexplored. Methods: A detailed questionnaire, developed and validated by a panel of cTTP experts, was distributed to healthcare professionals and patient associations to gather comprehensive data on the economic and social burden of cTTP in Italy. The study was focused on direct and indirect costs associated with the disease management of 15 patients with cTTP, as well as out-of-pocket expenses incurred by patients. Results: The analysis revealed that of the 15 patients diagnosed with cTTP in Italy, 60% were adults aged 40-55 years. Productivity loss and diminished quality of life dominated the economic burden of cTTP, accounting for 81.05% of total costs. Direct medical costs, while substantial, represented a smaller portion of the overall financial impact. Additionally, out-of-pocket expenses, though constituting the smallest fraction, underscored the financial contributions made by patients towards their own care management. Conclusion: The findings underscore the need for a multidisciplinary and holistic approach to cTTP management that extends beyond the clinical treatment. Addressing the economic and social implications of the disease is crucial for improving patient well-being and ensuring the sustainability of healthcare systems. The study advocates for increased awareness, research, and access to care for cTTP patients, highlighting the importance of comprehensive support networks to mitigate the disease’s broader societal impacts, estimated to be around 2 million euro for 15 patients in 10 years.

A Machine Learning Approach to Identifying Risk Factors for Long COVID-19

Long-term sequelae of coronavirus disease 2019 (COVID-19) infection are common and can have debilitating consequences. There is a need to understand risk factors for Long COVID-19 to give impetus to the development of targeted yet holistic clinical and public health interventions to reduce its associated healthcare and economic burden. Given the large number and variety of predictors implicated spanning health-related and sociodemographic factors, machine learning becomes a valuable tool. As such, this study aims to employ machine learning to produce an algorithm to predict Long COVID-19 risk, and thereby identify key predisposing factors. Longitudinal cohort data were sourced from the UK’s “Understanding Society: COVID-19 Study” (n = 601 participants with past symptomatic COVID-19 infection confirmed by serology testing). The random forest classification algorithm demonstrated good overall performance with 97.4% sensitivity and modest specificity (65.4%). Significant risk factors included early timing of acute COVID-19 infection in the pandemic, greater number of hours worked per week, older age and financial insecurity. Loneliness and having uncommon health conditions were associated with lower risk. Sensitivity analysis suggested that COVID-19 vaccination is also associated with lower risk, and asthma with an increased risk. The results are discussed with emphasis on evaluating the value of machine learning; potential clinical utility; and some benefits and limitations of machine learning for health science researchers given its availability in commonly used statistical software.

8.E. Skills building seminar: Methods for measuring the true health cost of pollution

Abstract Healthy environments are essential for physical and mental wellbeing. Air pollution is considered to be one of the most significant environmental risk factors for ill health and premature death within the European Union. Poor air and noise quality have been linked to the exacerbation of symptoms, hospital admissions, and even premature deaths, especially for those with cardiorespiratory diseases. The associated medical costs and productivity losses therefore also impose a large economic cost. Exposure to environmental stressors disproportionately affects socially disadvantaged groups, and therefore contributes to the large socioeconomic inequities in health observed persistently in Europe. The EU has prioritised action on causes of pollution. For example, its Green Deal outlines ambitious plans to address climate challenges such as pollution and align air quality ambitions closer to the World Health Organization guidelines. Likewise, the European Environmental Agency routinely monitors the mortality burden associated with air pollution, while the impact of environmental noise on European citizens is examined through the Environmental Noise Directive. While in the political scene there is interest to advance the reduction of pollution, efforts are hindered by the lack of an harmonized methodology to quantify the socioeconomic cost of environmental stressors. Currently, researchers working with the burden of disease framework face many challenges in its application in the context of environmental stressors. Among others, these challenges include unmet data needs and major lack of transparency in methodological developments. In this skills-building seminar, we will outline an integrated approach for measuring the true health cost of pollution. This approach is currently being trialled in the EU-funded BEST-COST project, which sets out to improve methodologies for understanding the socioeconomic cost of environmental stressors, focusing on air and noise pollution. The project brings together a consortium of 17 partners from Europe and the USA, and is led by Sciensano, the Belgian institute for health. Through a synergy of theoretical outlines and real-life examples, seminar participants will gain methodological insights in the three key components of this integrated approach - i.e., the quantification of the health burden of environmental stressors via comparative risk assessment, the monetization of Disability-Adjusted Life Years to assess economic impact, and the quantification of environmental health inequalities via a novel area-level based framework. Key messages • There are significant unmet needs with respect to both data and methodologies for quantifying the socioeconomic cost of environmental stressors. • We outline an integrated approach for measuring the true health cost of pollution, combining health burden, economic burden, and environmental health inequalities.

Health burden and economic costs of vector-borne diseases in Italy: the AUSL Romagna case

Abstract Introduction Vector-borne diseases (VBDs) are a serious threat for global health, representing around 17% of communicable diseases and more than 700.000 deaths every year. In Europe, and especially in Italy, this is a subject of growing concern, due to the increase of VBDs outbreaks that need vector control plans. Objectives Evaluate the 2013-2022 trend of VBD outbreaks within the AUSL Romagna area (provinces of Ravenna, Rimini, and Forlì-Cesena, in Emilia-Romagna Region, Italy) and the economic impact caused by hospitalizations and local prevention/disinfestation treatments. Methods We used aggregated and anonymized data from 3 informative systems: communicable disease system (SMI) for VBD prevalence; hospital discharge records (SDO) for hospitalizations, with a contribution of the VBD-related Diagnosis Related Groups (DRG); municipality records regarding the cost of dedicated interventions for vector prevention and disinfestation, communicated to the Emilia-Romagna Region. Results For the area of interest, 479 cases of VBDs were notified from 2013 to 2022, with a slight increasing trend over the years. Through hospital SDOs, 252 cases were identified with a diagnosis of VBD, plus 283 with a VBD-related DRG, with a total expenditure of €9.587.777. The distribution was not uniform between the provinces, Ravenna having the highest expense. The municipality records highlighted expenses for €95.443 for prevention and control interventions against mosquitoes, with a very variable trend over the period considered. Forlì had the highest expense. Conclusions VBDs show a highly variable trend and distribution during time, also in relatively small, sub-regional areas. The Emilia-Romagna regional plan against arboviruses, annually updated, can contribute to reduce this specific health and economic burden, lowering transmission among the population and resulting hospital pressure, thanks to prevention and timely interventions. Key messages • The use of information systems enables monitoring of the impact of arboviruses, as well as the related cost for hospital care and local treatments. • Putting in place an effective and updated plan against arboviruses, like the Emilia-Romagna Region one, helps managing VBDs and mitigating economic costs.

Unveiling pharmacogenomics: insights from Portuguese pharmacists on quaternary prevention

Abstract Background Public health genomics recognises the potential of genomic knowledge for enhancing population health. Adverse drug reactions (ADR) and lack of efficacy have significant clinical and economic burdens, which can be mitigated by pharmacogenomics (PGx) testing. Pharmacists can play a vital role in facilitating the implementation of PGx into routine clinical care. This will promote quaternary prevention, to protect individuals from medical intervention that can cause more harm than good. Objectives To assess attitudes, opinions, expectations, practices, and concerns of Portuguese pharmacists regarding PGx implementation. Methods An observational cross-sectional web-based survey was developed based on literature review, adapted to the national context, and validated in a focus group. The target population were adults residing in Portugal with a degree in Pharmaceutical Sciences or equivalent, with convenience sampling. Descriptive statistics were performed. Results From 303 participants, 98% believe that PGx is an important area of pharmaceutical sciences and 97% indicate that PGx should be included in continuing education. Almost all (99%) anticipate that PGx implementation will prevent the administration of ineffective drugs and inappropriate doses, 98% expect PGx will reduce ADR. Major concerns are related with direct-to-consumer sale of PGx tests via internet (78%) and unauthorized access to test results (91%). Currently, 25% are familiar with reliable sources of information on PGx, but only 11% feel qualified to recommend PGx testing, and 10% have analysed PGx reports. Conclusions There are positive opinions and expectations regarding the potential benefits of PGx tests. However, there are regulatory concerns and lack of readiness for immediate application. Pharmacists express interest in learning more about PGx, highlighting the need for continuous education and training to integrate it effectively into routine pharmaceutical practice. Key messages • Pharmacists recognize the benefits of PGx implementation for quaternary prevention. • Regulatory concerns and readiness gaps in PGx emphasise a need for training and life-long education of pharmacists.

Comparative Analysis of Osteoarthritis Therapeutics: A Justification for Harnessing Retrospective Strategies via an Inverted Pyramid Model Approach

In this review, we seek to explore two distinct approaches to the clinical management of OA: a prospective approach, addressing primarily one’s genetic predisposition to OA and generating early intervention options, and the retrospective approach, aimed at halting or reversing OA progression post-symptom onset. The clinical management of OA remains challenging, largely due to the limited availability of preventative treatments and failure of existing therapies to modify or reverse the underlying pathophysiology. The prospective approach involves the identification of genetic markers associated with OA and utilizes in vitro and in vivo models to characterize the underlying disease mechanism. Further, this approach focuses on identifying genetic predispositions and unique molecular subtypes of OA to develop individualized treatment plans based on patient genotypes. While the current literature investigating this strategy has been notable, this approach faces substantial challenges, such as extensive time burdens and utilization of extensive genetic testing that may not be economically feasible. Additionally, there is questionable justification for such extensive investigations, given OA’s relatively low mortality rates and burden when contrasted with diseases like specific forms of cancer, which rely heavily on the prospective approach. Alternatively, the retrospective approach primarily focuses on intervention following symptom onset and aims to utilize novel therapeutics to slow or reverse the inflammatory cascade typically seen in disease progression. These treatments, like Hippo pathway inhibitors, have shown initial promise in halting OA progression and alleviating OA symptomology by modulating cellular processes to preserve articular cartilage. In comparison to the prospective approach, the retrospective strategy is likely more cost-effective, more widely applicable, and does not necessitate thorough and invasive genetic screening. However, this approach must still be weighed against the typical natural history of disease progression, which frequently results in total knee arthroplasty and unacceptable outcomes for 15–20% of patients. From a comparative analysis of these two approaches, this review argues that the retrospective strategy, with ideally lower time and economic burden and greater accessibility, offers a more reasonable and effective solution in the context of OA management. Using a similar approach to other management of chronic diseases, we suggest an “Inverted Pyramid” model algorithm, a structured research and development regimen that prioritizes generating widely effective therapies first, with subsequent refinement of treatments based on the development of patient resistance to these therapies. We argue that this strategy may reduce the need for total knee arthroplasty while improving patient outcomes and accessibility.

Neutrophil-Mimetic Upconversion Photosynthetic Nanosystem Derived from Microalgae for Targeted Treatment of Thromboembolic Stroke.

Thromboembolic stroke constitutes the majority of brain strokes, resulting in elevated mortality and morbidity rates, as well as significant societal and economic burdens. Although intravenous thrombolysis serves as the standard clinical treatment, its narrow therapeutic window and the inflammatory response induced by tissue plasminogen activator (tPA) administration limit its efficacy. In the initial stages of stroke, the abrupt cessation of blood flow leads to an energy metabolism disorder, marked by a substantial decrease in adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide phosphate (NADPH) levels, causing irreversible damage to neural cells. In this study, we introduce a neutrophil-mimetic, microalgae-derived upconversion photosynthetic nanosystem designed for targeted treatment of thromboembolic stroke. This system features upconversion nanoparticles coated with a thylakoid membrane and wrapped in an activated neutrophil membrane, further decorated with ROS-responsive thrombolytic tPA on its surface. The neutrophil-mimetic design facilitates high targeting specificity and accumulation at the thrombus site after intravenous administration. Upon exposure to elevated levels of reactive oxygen species (ROS) at the thrombus location, the nanosystem promptly demonstrated potent thrombolytic efficacy through the surface-modified tPA. Furthermore, near-infrared II (NIR-II) laser irradiation activated the generation of ATP and NADPH, which inhibited inflammatory cell infiltration, platelet activation, oxidative stress, and neuronal injury. This constructed nanoplatform not only showcases exceptional targeting efficiency at the stroke site and controllable release of the thrombolytic agent but also facilitates ATP/NADPH-mediated thrombolytic, anti-inflammatory, antioxidative stress, and neuroprotective effects. Additionally, it offers valuable insights into the potential therapeutic applications of microalgae-based derivatives in managing thromboembolic stroke.