Modelling Health and Healthcare for an Ageing Population

Population ageing has received much attention as a contributing cause of spiralling healthcare expenditure. This study primarily aims to estimate the impact of population ageing on key diseases, and to develop a flexible modelling framework that can inform policy decisions. This research provides a proof-of-concept model where individual Discrete Event Simulation models for three diseases (heart disease, Alzheimer’s disease, and osteoporosis) were extended from existing published models to simulate the general UK population aged 45 years and older, and combined within a single model. Using external population projection data incorporating potential demographic changes, the methods for projecting future healthcare expenditures for the three diseases were demonstrated and the relative benefits of improving treatment of each of the diseases evaluated. Secondary outcomes include the development of a pragmatic literature search method which can be used for literature within diffuse topic areas, and a literature repository for future researchers to explore the existing literature on ageing and healthcare expenditure. Expenditure for the three diseases is projected to increase from £16 billion in 2012 to £28 billion in 2037. A key finding from this work is that the estimates of costs, quality-adjusted life years (QALYs), and the projected expenditure for healthcare services can differ when multiple diseases are modelled in a single model compared with the summed results from single disease models. This implies that policy decisions on the allocation and planning of healthcare resources based on the results from individual disease models can be different from those based on linked models. The novel approach of linking multiple disease models with correlations incorporated provides a new methodological option primarily for modellers who undertake research on comorbidities. It also has potential for wider applications in informing decisions on commissioning of healthcare services and long-term priority setting across diseases and healthcare programmes, hence ultimately contributing to the improvement of population health

Interaction of Apoptotic Cells with Macrophages Upregulates COX-2/PGE 2

Recognition of apoptotic cells by macrophages is crucial for resolution of inflammation, immune tolerance, and tissue repair. Cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) and hepatocyte growth factor (HGF) play important roles in the tissue repair process. We investigated the characteristics of macrophage COX-2 and PGE2 expression mediated by apoptotic cells and then determined how macrophages exposed to apoptotic cells in vitro and in vivo orchestrate the interaction between COX-2/PGE2 and HGF signaling pathways. Exposure of RAW 264.7 cells and primary peritoneal macrophages to apoptotic cells resulted in induction of COX-2 and PGE2. The COX-2 inhibitor NS-398 suppressed apoptotic cell-induced PGE2 production. Both NS-398 and COX-2-siRNA, as well as the PGE2 receptor EP2 antagonist, blocked HGF expression in response to apoptotic cells. In addition, the HGF receptor antagonist suppressed increases in COX-2 and PGE2 induction. The in vivo relevance of the interaction between the COX-2/PGE2 and HGF pathways through a positive feedback loop was shown in cultured alveolar macrophages following in vivo exposure of bleomycin-stimulated lungs to apoptotic cells. Our results demonstrate that upregulation of the COX-2/PGE2 and HGF in macrophages following exposure to apoptotic cells represents a mechanism for mediating the anti-inflammatory and antifibrotic consequences of apoptotic cell recognition

BAYESIAN META-ANALYSIS ON MEDICAL DEVICES: APPLICATION TO IMPLANTABLE CARDIOVERTER DEFIBRILLATORS

Objectives: The aim of this study is to describe and illustrate a method to obtain early estimates of the effectiveness of a new version of a medical device

A Case of Congenital Common Bile Duct Web Treated with Balloon Dilation under Endoscopic Retrograde Cholangiopancreatography in a Young Child

Web in common bile duct (CBD web) is very rare. It is usually asymptomatic and detected incidentally during surgery for other causes in adults. It can be congenital or acquired, however congenital CBD web is extremely rare. Currently, despite its invasiveness and complications, endoscopic retrograde cholangiopancreatography (ERCP) is considered as a useful diagnostic and therapeutic modality in children with hepatobiliary pancreatic diseases as in adults. Herein we report a case of congenital CBD web presenting with acute pancreatitis and choledocholithiasis in a 4-year-old girl which was diagnosed and treated using balloon dilation under ERCP. After balloon dilation of the web, a common pancreatobiliary channel was observed. To the best of our knowledge, a case of congenital CBD web with pancreatobiliary junctional abnormality treated using ERCP in a child has not been reported to date

Emission Rates of Volatile Organic Compounds Released from Newly Produced Household Furniture Products Using a Large-Scale Chamber Testing Method

The emission rates of volatile organic compounds (VOCs) were measured to investigate the emission characteristics of five types of common furniture products using a 5 m3 size chamber at 25°C and 50% humidity. The results indicated that toluene and α-pinene are the most dominant components. The emission rates of individual components decreased constantly through time, approaching the equilibrium emission level. The relative ordering of their emission rates, if assessed in terms of total VOC (TVOC), can be arranged as follows: dining table > sofa > desk chair > bedside table > cabinet. If the emission rates of VOCs are examined between different chemical groups, they can also be arranged in the following order: aromatic (AR) > terpenes (TER) > carbonyl (CBN) > others > paraffin (PR) > olefin (HOL) > halogenated paraffin (HPR). In addition, if emission strengths are compared between coated and uncoated furniture, there is no significant difference in terms of emission magnitude. Our results indicate that the emission characteristics of VOC are greatly distinguished between different furniture products in terms of relative dominance between different chemicals

Fabrication of graphene-based electrode in less than a minute through hybrid microwave annealing

Highly efficient and stable MoS 2 nanocrystals on graphene sheets (MoS 2 /GR) are synthesized via a hybrid microwave annealing process. Through only 45 second-irradiation using a household microwave oven equipped with a graphite susceptor, crystallization of MoS 2 and thermal reduction of graphene oxide into graphene are achieved, indicating that our synthetic method is ultrafast and energy-economic. Graphene plays a crucial role as an excellent microwave absorber as well as an ideal support material that mediates the growth of MoS 2 nanocrystals. The formed MoS 2 /GR electrocatalyst exhibits high activity of hydrogen evolution reaction with small onset overpotential of 0.1 V and Tafel slope of 50mV per decade together with an excellent stability in acid media. Thus our hybrid microwave annealing could be an efficient generic method to fabricate various graphene-based hybrid electric materials for broad applications.open2

Prevalence of human parechovirus and enterovirus in cerebrospinal fluid samples in children in Jinju, Korea

PurposeHuman parechovirus (HPeV) and enterovirus (EV) are causative agents of a sepsis-like illness in neonates and of infections of the central nervous system in young children. The objectives of this study were to assess the prevalence of HPeV3 and EV infection in young children with a sepsis-like illness or with meningitis in Jinju, Korea.MethodsCerebrospinal fluid (CSF) samples were collected from 267 patients (age range, 1 day to 5 years) and assessed for HPeV and EV by performing reverse transcription polymerase chain reaction assay. Amplification products of the VP3/VP1 region of HPeV and of the VP1 region of EV were sequenced to identify the virus type.ResultsHPeV and EV were detected in 3.4% and 7.5% of the total CSF samples assessed, respectively. The age distribution of EV-positive patients (median age, 1.4 months) had a significantly broader range than that of HPeV-positive patients (median age, 7.8 months). The peak seasons for HPeV and EV infection were spring and summer, respectively. The clinical symptoms for HPeV and EV infection were similar, and fever was the most common symptom. Pleocytosis was detected in 22.2% of HPeV-positive patients and 35.5% of EV-positive patients. The VP3/VP1 gene sequence of the nine Korean strains clustered most closely with the Japanese strain (AB759202).ConclusionThe data indicate that HPeV infection is predominant in young infants (<6 months) and that meningitis without pleocytosis was caused by both HPeV and EV infection in children

Therapeutic Co-targeting of WEE1 and ATM Downregulates PD-L1 Expression in Pancreatic Cancer

Purpose Pancreatic cancer (PC) is one of the most lethal cancers worldwide, but there are currently no effective treatments. The DNA damage response (DDR) is under investigation for the development of novel anti-cancer drugs. Since DNA repair pathway alterations have been found frequently in PC, the purpose of this study was to test the DDR-targeting strategy in PC using WEE1 and ATM inhibitors. Materials and Methods We performed in vitro experiments using a total of ten human PC cell lines to evaluate antitumor effect of AZD1775 (WEE1 inhibitor) alone or combination with AZD0156 (ATM inhibitor). We established Capan-1-mouse model for in vivo experiments to confirm our findings. Results In our research, we found that WEE1 inhibitor (AZD1775) as single agent showed anti-tumor effects in PC cells, however, targeting WEE1 upregulated p-ATM level. Here, we observed that co-targeting of WEE1 and ATM acted synergistically to reduce cell proliferation and migration, and to induce DNA damage in vitro. Notably, inhibition of WEE1 or WEE1/ATM downregulated programmed cell death ligand 1 expression by blocking glycogen synthase kinase-3 beta serine 9 phosphorylation and decrease of CMTM6 expression. In Capan-1 mouse xenograft model, AZD1775 plus AZD0156 (ATM inhibitor) treatment reduced tumor growth and downregulated tumor expression of programmed cell death ligand 1, CMTM6, CD163, and CXCR2, all of which contribute to tumor immune evasion. Conclusion Dual blockade of WEE1 and ATM might be a potential therapeutic strategy for PC. Taken together, our results support further clinical development of DDR-targeting strategies for PC.

Modeling the Economic Impact of Interventions for Older Populations with Multimorbidity: A Method of Linking Multiple Single-Disease Models

Introduction. Individuals from older populations tend to have more than 1 health condition (multimorbidity). Current approaches to produce economic evidence for clinical guidelines using decision-analytic models typically use a single-disease approach, which may not appropriately reflect the competing risks within a population with multimorbidity. This study aims to demonstrate a proof-of-concept method of modeling multiple conditions in a single decision-analytic model to estimate the impact of multimorbidity on the cost-effectiveness of interventions. Methods. Multiple conditions were modeled within a single decision-analytic model by linking multiple single-disease models. Individual discrete event simulation models were developed to evaluate the cost-effectiveness of preventative interventions for a case study assuming a UK National Health Service perspective. The case study used 3 diseases (heart disease, Alzheimer’s disease, and osteoporosis) that were combined within a single linked model. The linked model, with and without correlations between diseases incorporated, simulated the general population aged 45 years and older to compare results in terms of lifetime costs and quality-adjusted life-years (QALYs). Results. The estimated incremental costs and QALYs for health care interventions differed when 3 diseases were modeled simultaneously (£840; 0.234 QALYs) compared with aggregated results from 3 single-disease models (£408; 0.280QALYs). With correlations between diseases additionally incorporated, both absolute and incremental costs and QALY estimates changed in different directions, suggesting that the inclusion of correlations can alter model results. Discussion. Linking multiple single-disease models provides a methodological option for decision analysts who undertake research on populations with multimorbidity. It also has potential for wider applications in informing decisions on commissioning of health care services and long-term priority setting across diseases and health care programs through providing potentially more accurate estimations of the relative cost-effectiveness of interventions