P016 Impact of Non-Remission on Health-Related Quality of Life and Patient Reported Outcomes in Patients With Crohn's Disease: Targeted Literature Review.

BACKGROUND: Crohn's disease (CD) leads to chronic inflammation of the gastrointestinal tract that significantly impacts patients over an entire lifetime. The decrease in health-related quality of life (HRQoL) may have an impact on patient's level of functioning, work productivity, and other activities. The goal of treatment for CD is clinical remission based on clinical, endoscopic, and biological parameters. There has been introduction of new treatments in recent years. A review was conducted to assess the impact of non-remission on HRQoL and patient reported outcomes (PROs) in patients with CD. METHODS: Literature search of English language publications from 2015-2021 was conducted in Embase® and MEDLINE®. Real world studies meeting predefined criteria (adult CD patients in non-remission presenting data for HRQoL or PROs) were included in the review. Data on study characteristics, disease characteristics, HRQoL and PROs were extracted from the included studies. RESULTS: The review retrieved 1384 records from which only 10 studies presented data for HRQoL and/or PROs. The definition of remission varied across the included studies. In most studies (90%), remission was defined using Harvey-Bradshaw Index and/or Crohn's disease activity index. Different tools were used to assess HRQoL and sleep quality. In a study, no normalization of long-term HRQoL was observed in patients who did not achieve clinical remission. A negative correlation was found between utility indexes & disease activity in a study (ρ = -0.586, p < 0.001). A significant correlation was also observed in a study between HRQoL and disease activity where HRQoL in patients with active disease was poor compared to patients in remission. The HRQoL domains of anxiety, depression and pain were impacted in non-remitters. The mean IBDQ score was 189 ± 16.1 in remitters and 145 ± 15.9 in non-remitters (p < 0.001). A strong negative correlation between IBDQ and disease activity was reported by a study. In a study, work productivity was moderately but significantly correlated with disease activity indicating reduction in work productivity of patients with active disease (mild, moderate, and severe) compared to remitters. In another study, severe disease activity was significantly associated with an increased amount of fragmented sleep. Patients with moderate to severe disease had a significantly longer time awake after falling asleep compared to patients in remission or with mild disease activity (65.8 minutes, 44.3 minutes, 49.1 minutes, respectively). Patients with active disease also reported poor sleep quality and suffered from excessive daytime sleepiness. There was a significant difference in the median sleep efficiency for patients with moderate to severe disease compared to patients with remission. CONCLUSION: This targeted review found in general that not being able to achieve/maintain remission had an impact on the HRQoL of patients with CD. Patients not achieving remission were associated with decreased work productivity, poor sleep quality, lower sleep efficiency, daytime sleepiness and poor HRQoL. However, studies assessing HRQoL and PROs in the real-world are scarce, with discrepancies based on remission status. Further research is warranted, and health care providers and payers should consider the impact of therapies on the improvement in HRQoL of patients with CD.

P025 The Impact of Non-Remission on Costs and Resource Use In Patients With Crohn's Disease: Targeted Literature Review.

BACKGROUND: The incidence of Crohn's disease (CD) has been rising globally. Patients with CD are at an increased risk of mortality compared to general population. The goal of treatment for CD is clinical remission based on clinical, endoscopic, and biological parameters. There has been introduction of new treatments in recent years. A review was conducted to assess the impact of non-remission on cost and resource use in patients with CD. METHODS: Literature search of English language publications from 2015-2021 was conducted in Embase® and MEDLINE®. Real world studies meeting predefined review criteria were included and data were extracted in pre-defined extraction form. RESULTS: The review retrieved 1384 records; 24 fulfilled eligibility criteria. The definition of remission varied across the included studies. In most studies (66.67%), remission was defined using Crohn's disease activity index and/or Harvey-Bradshaw Index. Among included evidence, 21 studies reported proportion of non-remitters undergoing surgery, 11 studies reported the data for hospitalizations and 2 studies reported cost of treatment for non-remitters. Proportion of non-remitters requiring hospitalizations ranged from 6.7% to 30.6%. Univariate analysis suggested that deep remission was significantly associated with lower hazards for being hospitalized (HR: 0.18 [95%CI: 0.08, 0.25]); suggesting a significantly higher risk of hospitalization in non-remitters. In a study, the mean duration of cumulative hospital stays was significantly higher in patients with a pathological MRI (19.7 ± 7.4 days) compared to patients in deep remission (0.75 ± 0.52 days, p < 0.05). The proportion of non-remitters undergoing surgery ranged from 1.5% to 57%. The proportion of patients undergoing surgery were high in non-remitters compared to remitters. Hematopoietic stem cell transplantation was needed in 4.1% non-remitters and repeat surgery in 3.5% non-remitters. In a study, surgery was required by 11.6% patients with no healing (due to refractory strictures, penetrating complications, and severe refractory disease) and 11.5% patients presenting with mucosal healing (due to structuring and penetrating complications), while no patient with transmural healing required surgery. Non-remission led to higher total costs, especially in patients undergoing surgery or dependent on in-hospital administrated drugs. The costs were 4 to 6 times higher in patients in an active period and 19 times higher for patients requiring surgery compared to patients in remission. Adjusted total indirect cost among participants with disease remission was reduced by 60% compared to patients with active disease (€243.44 per patient per month, p < 0.001). The number of consultations in the last month, monthly consultation cost, current treatment cost, amount of benefits from public organisations, and self-reported expenses on all categories were significantly higher in non-remitters compared to patients in remission. CONCLUSION: This targeted review found in general that not being able to achieve/maintain remission has an impact on the economic outcomes of patients with CD. Non-remission in patients with CD was associated with an increased number of hospitalizations and surgeries. The cost of treatment for non-remitters was significantly higher than patients in remission. None of the studies presented data for patients who respond to treatment but are not able to achieve remission. Further research is warranted in these patients.

Indirect costs associated with ulcerative colitis: a systematic literature review of real-world data.

BACKGROUND: The economic burden of ulcerative colitis (UC), specifically related to indirect costs, is not extensively documented. Understanding and quantifying it is required by health care decision makers. AIM: To assess the impact of indirect costs of UC in observation studies. METHOD: A systematic literature search was conducted in MEDLINE®, Embase® and Cochrane Library to capture all relevant publications reporting outcomes on absenteeism, presenteeism and productivity losses in moderate to severe UC. Eligibility criteria for inclusion into the review were established using a predefined PICOS scheme. All costs were adjusted to 2017 currency values (USD dollars, $). RESULTS: In total, 18 studies reporting data on indirect costs were included in the analysis. Absenteeism costs were classified into three categories: sick leave, short-term and long-term disability. Most of the studies captured absenteeism costs related specifically to sick leave, which was experienced on average by 10 to 24% patients with UC. Only three studies captured presenteeism costs, as these are difficult to measure, however costs ranged from 1602 $ to 2947 $ per patient year. The proportion of indirect costs accounted for 35% of total UC costs (Total UC costs were defined as the sum of healthcare costs, productivity costs and out-of-pocket costs). DISCUSSION: A limited number of studies were identified describing the indirect costs in patients with moderate to severe UC. Insufficient data on different components of costs allowed a limited analysis on the impact of indirect costs in patients with UC. Further studies are needed to gain an understanding of the influence of UC on patients' functional abilities.

Impact of poor medication adherence on clinical outcomes and health resource utilization in patients with hypertension and/or dyslipidemia: systematic review.

INTRODUCTION: We aimed to summarize evidence on the effect of poor medication adherence on clinical outcomes and health resource utilization (HRU) among patients with hypertension and/or dyslipidemia. AREAS COVERED: A systematic review of studies reporting clinical outcomes and HRU for patients by status of adherence to antihypertensives and/or lipid-lowering medications was searched using Embase, MEDLINE, and MEDLINE In-Process and supplemented by manual searches of conference abstracts. In total, 45 studies were included, with most being retrospective observational studies (n = 36). Patients with poor adherence to antihypertensives and lipid-lowering medications compared with those with good adherence showed less reduction of blood pressure (BP) and low-density lipoprotein cholesterol (LDL-c) after 6-12 months follow-up (∆ systolic BP: 1.2 vs. -4.5 mmHg; ∆LDL-c: -14.0 to -18.9 vs. -34.1 to -42.0 mg/dL). Poor adherence was also significantly associated with a higher risk of cardiovascular events (HR: 1.1-1.9) and mortality (HR: 1.4-1.8) in patients with hypertension and dyslipidemia and increased HRU (i.e. outpatient visits, risk of cardiovascular-related and all-cause hospitalization, annual inpatient days, total health-care costs). EXPERT OPINION: Poor adherence is associated with poor clinical outcomes and increased HRU, highlighting the need to enhance medication adherence in patients with hypertension and/or dyslipidemia.

High blood pressure is a leading cause of death and disease burden followed by high lipid levels in blood. Due to the silent nature of the diseases, patients can fall short of optimal medicinal treatment adherence and persistence, leading to poor outcomes and disease complications. The effectiveness of medicinal interventions depends on the appropriate medication-taking behavior of patients as lower adherence can lead to poor treatment benefits. Research was conducted to look for published studies that assessed the effect of lower medication adherence on clinical outcomes and health resource use among patients with high blood pressure, high lipid levels in blood, or both. Researchers were able to find 45 already published studies, from which 32 evaluated the use of blood pressure lowering medications and 7 evaluated the use of lipid-lowering medications, while 6 included patients treated with both types of medications. Refill of pharmacy prescription records was the most common method of assessing treatment adherence. Researchers found that patients with lower adherence to these medications compared with those with good adherence showed less decrease in blood pressure levels and less improvement in blood lipid levels after 6­12 months of follow-up. Patients who had lower adherence also had higher rates of cardiovascular events and deaths and increased usage of health services including visits to outpatient clinics, getting admitted to hospitals, and a longer stay of hospitalizations, leading to a higher overall healthcare cost. These findings suggest lower adherence is associated with poor clinical outcomes and increased health-care resource usage, highlighting the need to improve medication adherence in patients with high blood pressure and high lipid levels in blood.

Unlocking the Value: Quantifying the Return on Investment of Hospital Artificial Intelligence.

PURPOSE: A comprehensive return on investment (ROI) calculator was developed to evaluate the monetary and nonmonetary benefits of an artificial intelligence (AI)-powered radiology diagnostic imaging platform to inform decision makers interested in adopting AI. METHODS: A calculator was constructed to calculate comparative costs, estimated revenues, and quantify the clinical value of using an AI platform compared with no use of AI in radiology workflows of a US hospital over a 5-year time horizon. Parameters were determined on the basis of expert interviews and a literature review. Scenario and deterministic sensitivity analyses were conducted to evaluate calculator drivers. RESULTS: In the calculator, the introduction of an AI platform into the hospital radiology workflow resulted in labor time reductions and delivery of an ROI of 451% over a 5-year period. The ROI was increased to 791% when radiologist time savings were considered. Time savings for radiologists included more than 15 8-hour working days of waiting time, 78 days in triage time, 10 days in reading time, and 41 days in reporting time. Using the platform also provided revenue benefits for the hospital in bringing in patients for clinically beneficial follow-up scans, hospitalizations, and treatment procedures. Results were sensitive to the time horizon, health center setting, and number of scans performed. Among those, the most influential outcome was the number of additional necessary treatments performed because of AI identification of patients. CONCLUSIONS: The authors demonstrate a substantial 5-year ROI of implementing an AI platform in a stroke management-accredited hospital. The ROI calculator may be useful for decision makers evaluating AI-powered radiology platforms.

Surface-Enhanced Raman Spectroscopy of Ammonium Nitrate Using Al Structures, Fabricated by Laser Processing of AlN Ceramic.

This work presents results on laser-induced surface structuring of AlN ceramic and its application in Surface-Enhanced Raman Spectroscopy (SERS). The laser processing is performed by nanosecond pulses in air and vacuum. Depending on the processing conditions, different surface morphology can be obtained. The ablation process is realized by ceramic decomposition as the formation of an aluminium layer is detected. The efficiency of the fabricated structures as active substrates in SERS is estimated by the ability of the detection of ammonium nitrate (NH4NO3). It is conducted for Raman spectrometer systems that operate at wavelengths of 514 and 785 nm where the most common commercial systems work. The obtained structures contribute to enhancement of the Raman signal at both wavelengths, as the efficiency is higher for excitation at 514 nm. The limit of detection (LOD) of ammonium nitrate is estimated to be below the maximum allowed value in drinking water. The analysis of the obtained results was based on the calculations of the near field enhancement at different conditions based on Finite Difference Time Domain simulation and the extinction spectra calculations based on Generalized Mie scattering theory. The structures considered in these simulations were taken from the SEM images of the real samples. The oxidation issue of the ablated surface was studied by X-ray photoelectron spectroscopy. The presented results indicated that laser structuring of AlN ceramics is a way for fabrication of Al structures with specific near-field properties that can be used for the detection of substances with high social impact.

Rare host variants in ciliary expressed genes contribute to COVID-19 severity in Bulgarian patients.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a pneumonia with extremely heterogeneous clinical presentation, ranging from asymptomatic to severely ill patients. Previous studies have reported links between the presence of host genetic variants and the outcome of the COVID-19 infection. In our study, we used whole exome sequencing in a cohort of 444 SARS-CoV-2 patients, admitted to hospital in the period October-2020-April-2022, to search for associations between rare pathogenic/potentially pathogenic variants and COVID-19 progression. We used gene prioritization-based analysis in genes that have been reported by host genetic studies. Although we did not identify correlation between the presence of rare pathogenic variants and COVID-19 outcome, in critically ill patients we detected known mutations in a number of genes associated with severe disease related to cardiovascular disease, primary ciliary dyskinesia, cystic fibrosis, DNA damage repair response, coagulation, primary immune disorder, hemoglobin subunit ß, and others. Additionally, we report 93 novel pathogenic variants found in severely infected patients who required intubation or died. A network analysis showed main component, consisting of 13 highly interconnected genes related to epithelial cilium. In conclusion, we have detected rare pathogenic host variants that may have influenced the COVID-19 outcome in Bulgarian patients.

Transplacental clastogenic and epigenetic effects of gold nanoparticles in mice.

The broad application of nanotechnology in medicine, biology, and pharmacology is leading to a dramatic increase of the risk of direct contact of nanoproducts, among which gold nanoparticles (AuNP), with the human organism. The present study aimed at evaluating in vivo the genotoxicity of AuNPs with average size of 40 nm and 100 nm. A single intraperitoneal treatment of adult male and female Swiss mice (strain H) with AuNPs, at a dose of 3.3 mg/kg body weight, had no effect on the frequency of micronucleated polychromatic erythrocytes (MN PCEs) in bone marrow. Conversely, the transplacental treatment with AuNP-100 nm, but not with AuNP-40 nm, applied intraperitoneally at a dose of 3.3 mg/kg to pregnant mice on days 10, 12, 14, and 17 of gestation, resulted in a significant increase in the frequency of MN PCEs in both liver and peripheral blood of mouse fetuses. In parallel, the same treatment with AuNP-100 nm, but not with AuNP-40 nm, produced significant changes in microRNA expression. In particular, out of 1281 mouse microRNAs analyzed, 28 were dys-regulated more than two-fold and to a statistically significant extent in fetus lung, and 5 were up-regulated in fetal liver. Let-7a and miR-183 were significantly up-regulated in both organs. The data presented herein demonstrate for the first time the transplacental size-dependent clastogenic and epigenetic effects of AuNPs in mouse fetus, thus highlighting new aspects concerning the putative genotoxicity of AuNPs during a vulnerable period of life.

Picosecond Pulsed Laser Deposition of Metals and Metal Oxides.

In this work, we present the fabrication of thin films/nanostructures of metals and metal oxides using picosecond laser ablation. Two sets of experiments were performed: the depositions were carried out in vacuum and in air at atmospheric pressure. The subjects of investigation were the noble metals Au and Pt and the metal oxides ZnO and TiO2. We studied and compared the phase composition, microstructure, morphology, and physicochemical state of the as-deposited samples' surfaces in vacuum and in air. It was found that picosecond laser ablation performed in vacuum led to the fabrication of thin films with embedded and differently sized nanoparticles. The implementation of the same process in air at atmospheric pressure resulted in the fabrication of porous nanostructures composed of nanoparticles. The ablation of pure Pt metal in air led to the production of nanoparticles with an oxide shell. In addition, more defects were formed on the metal oxide surface when the samples were deposited in vacuum. Furthermore, the laser ablation process of pure Au metal in a picosecond regime in vacuum and in air was theoretically investigated using molecular dynamics simulation.

Access to innovative drugs and the National Reimbursement Drug List in China: Changing dynamics and future trends in pricing and reimbursement.

BACKGROUND AND OBJECTIVES: Multiple reforms aimed at improving the Chinese population's health have been introduced in recent years, including several designed to improve access to innovative drugs. We sought to review current factors affecting access to innovative drugs in China and to anticipate future trends. METHODS: Targeted reviews of published literature and statistics on the Chinese healthcare system, medical insurance and reimbursement processes were conducted, as well as interviews with five Chinese experts involved in the reimbursement of innovative drugs. RESULTS: Drug reimbursement in China is becoming increasingly centralized due to the removal of provincial pathways, the establishment of the National Healthcare Security Administration and the implementation of the National Reimbursement Drug List (NRDL), which is now the main route for drug reimbursement in China. There is also an increasing number of other channels via which patients may access innovative treatments, including various types of commercial insurance and special access. Health technology assessment (HTA) and health economic evidence are becoming pivotal elements of the NRDL decision-making process. Alongside the optimization of HTA decision making, innovative risk-sharing agreements are anticipated to be increasingly leveraged in the future to optimize access to highly specialized technologies and encourage innovation while safeguarding limited healthcare funds. CONCLUSIONS: Drug public reimbursement in China continues to align more closely with approaches widely used in Europe in terms of HTA, health economics and pricing. Centralization of decision-making processes for public reimbursement of innovative drugs allows consistency in assessment and access, which optimizes the improvement of the Chinese population's health.

Impact of single-pill combinations versus free-equivalent combinations on adherence and persistence in patients with hypertension and dyslipidemia: a systematic literature review and meta-analysis.

OBJECTIVES: Hypertension is a leading cause of death and disease burden followed by dyslipidemia. Their asymptomatic nature leads to low adherence and persistence to treatments. A systematic literature review (SLR) investigated the impact of single-pill-combinations (SPC) compared to free-equivalent combination (FEC) on adherence, persistence, clinical outcomes, healthcare resource utilization (HCRU), and patient-reported outcomes, in patients with hypertension, dyslipidemia, or both. METHODS: MEDLINE, MEDLINE-IN-PROCESS, Embase, and Cochrane were searched from inception until 11 May 2021, for studies comparing SPC against FEC in patients with hypertension and/or dyslipidemia. Patient characteristics, study design, therapies, measures of adherence or persistence, clinical outcomes, and follow-up were extracted. RESULTS: Among 52 studies identified in the SLR, 27 (n = 346,030 patients) were included in the meta-analysis. SPCs were associated with significantly improved adherence compared with FEC, as assessed through medication-possession-ratio ≥80% (odds ratio (OR) 0.42, p < 0.01) and proportion of days covered ≥80% (OR 0.45, p < 0.01). SPC also improved persistence (OR 0.44, p < 0.01) and systolic blood pressure (SBP) reduction (mean difference -1.50, p < 0.01) compared with the FEC. CONCLUSIONS: SPC use resulted in significantly improved adherence, persistence, and SBP levels compared with FEC in patients with hypertension. The findings support SPC use in reducing the burden of hypertension and dyslipidemia.

High blood pressure is a leading cause of death and disease burden followed by high lipid levels in the blood. Due to the silent nature of the diseases, patients can fall short of optimal medical treatment adherence and persistence, leading to poor outcomes and disease complications. Simplification of the treatment regimen can be achieved using SPC therapies. The study was conducted to look for published studies that compared the use of SPC with FEC in patients with high blood pressure, high lipid levels in the blood, or both. The researchers were able to find 52 already published studies, of which, 27 studies reported adherence, persistence, and SBP reduction which were included in the data analysis. Researchers found SPCs to be associated with much greater improved adherence and persistence and a higher reduction in SBP when compared with FEC in high blood pressure patients. These findings support SPC use in reducing the burden of high blood pressure and high lipid levels in the blood.

Targeted literature review of the burden of extraintestinal pathogenic Escherichia Coli among elderly patients in Asia Pacific regions.

BACKGROUND: Extraintestinal Pathogenic Escherichia coli (ExPEC) is a leading cause of invasive disease, including bacteremia and sepsis. Invasive ExPEC disease (IED) has the potential to complicate the clinical treatment of other conditions and is associated with an increased mortality, hospitalization, and worse outcomes. Older adults and individuals with comorbid conditions are at higher risk of IED. ExPEC is of particular concern in the Asia Pacific region due to aging populations and rising antimicrobial resistance. OBJECTIVES: This study aimed to synthesize most recent data on the epidemiology, clinical and economic burden of IED in the elderly/high risk populations in China, Japan, South Korea, Taiwan, and Australia. METHODS: A targeted literature review was conducted using Embase, Medline, as well as local scientific databases. We included studies published in English and local languages published from January 1, 2010 to October 7, 2020 that were relevant to the research objectives. Studies were narratively synthesized. RESULTS: A total of 1,047 studies were identified and 34 of them were included in this review. ExPEC accounted for 46.0% (1,238/2,692) of bacteria-related invasive diseases in patients aged above 60 years in South Korea, followed by China (44.4% (284/640)), Taiwan (39.0% (1,244/3,194)), and Japan (18.1% (581/3,206)), while Australia reported ExPEC out of all pathogens (54.7% (4,006/7,330)) in general adults. Comorbidities such as diabetes or cancer were common in these patients. Studies reported increases in length-of-stay, and in-hospital 30-day all-cause mortality related to ExPEC associated bacteremia was between 9% to 12%. From a cost perspective, a 3-fold increase in sepsis-associated cost was reported in South Korea between 2005 and 2012. In Australia, antimicrobial resistance contributed to an additional cost of AUD $5.8 million per year (95% uncertainty interval [UI], $2.2-$11.2 million) in the treatment of bloodstream infections (BSIs). CONCLUSION: ExPEC was a major cause of blood stream infection across China, Japan, South Korea, Taiwan, and Australia. Both the clinical and economic burden associated to ExPEC infections as well as the antimicrobial resistance observed in the elderly call for preventive and curative actions in these regions.

Extraintestinal Pathogenic Escherichia coli (ExPEC) is a leading cause of invasive disease, including bacteremia and sepsis.A targeted literature review included the most recent data from 34 published studies on the epidemiology and clinical and economic burden of IED in the elderly/high risk populations in China, Japan, South Korea, Taiwan, and Australia.ExPEC accounted for 46.0% (1,238/2,692) of bacteria-related invasive diseases in patients aged above 60 years in South Korea, followed by China (44.4% (284/640)), Taiwan (39.0% (1,244/3,194)), and Japan (18.1% (581/3,206)), while Australia reported ExPEC out of all pathogens (54.7% (4,006/7,330)) in general adults. Studies reported increases in length-of-stay and in-hospital 30-day all-cause between 9% to 12%. These factors, along with antimicrobial resistance observed in the elderly, call for preventive and curative actions in these regions.Data for costs associated with ExPEC induced BSI or sepsis in this region are limited, but evidence shows increasing expenditures.

Targeted Literature Review of the Burden of Respiratory Syncytial Infection among High-Risk and Elderly Patients in Asia Pacific Region.

INTRODUCTION: The burden of respiratory syncytial virus (RSV), which causes acute respiratory illness, is well recognized among the pediatric population but also imposes a significant risk to the elderly (age ≥ 60) and those with underlying comorbidities. The study aimed to review the most recent data on epidemiology and burden (clinical and economic) of RSV in the elderly/high-risk populations in China, Japan, South Korea, Taiwan, and Australia. METHODS: A targeted review was conducted of English, Japanese, Korean, and Chinese language articles published from 1 January 2010 to 7 October 2020 relevant for the purpose. RESULTS: A total of 881 studies were identified, and 41 were included. The median proportion of elderly patients with RSV in all adult patients with acute respiratory infection (ARI) or community acquired pneumonia was 79.78% (71.43-88.12%) in Japan, 48.00% (3.64-80.00%) in China, 41.67% (33.33-50.00%) in Taiwan, 38.61% in Australia, and 28.57% (22.76-33.33%) in South Korea. RSV was associated with a high clinical burden on those patients with comorbidities such as asthma and chronic obstructive pulmonary disease. In China, inpatients with ARI showed a significantly higher rate of RSV-related hospitalization than outpatients (13.22% versus 4.08%, p < 0.01). The median length of hospital stay among elderly patients with RSV was longest in Japan (30 days) and shortest in China (7 days). Mortality data varied by region with some studies reporting rates as high as 12.00% (9/75) in hospitalized elderly patients. Finally, data on the economic burden was only available for South Korea, with the median cost of a medical admission for an elderly patient with RSV being US dollar (USD) 2933. CONCLUSION: RSV infection is a major source of disease burden among elderly patients, especially in regions with aging populations. It also complicates the management of those with underlying diseases. Appropriate prevention strategies are required to reduce the burden among the adult, especially the elderly, population. Data gaps regarding economic burden of RSV infection in the Asia Pacific region indicates the need for further research to increase our understanding on the burden of this disease in this region.

Risk Factors for Pulmonary Arterial Hypertension in Patients With Systemic Lupus Erythematosus: A Systematic Review and Expert Consensus.

OBJECTIVE: This study aimed to identify risk factors associated with the development of pulmonary arterial hypertension (PAH) in patients with systemic lupus erythematosus (SLE). METHODS: We conducted a systematic literature review of studies focusing on adult patients classified as having SLE-related PAH by searching the electronic databases Embase, Medline, Medline in-progress, Wanfang, China National Knowledge Infrastructure, Ichushi Web, Kmbase, and KoreaMed. Based on the findings, we conducted a Delphi survey to build expert consensus on issues related to screening for PAH in patients with SLE and on the importance and feasibility of measuring the identified factors in clinical practice. RESULTS: We included 21 eligible studies for data synthesis. Sixteen factors were associated with an increased risk of SLE-PAH: pericardial effusion, serositis, longer duration of SLE, arthritis, acute and subacute cutaneous lupus, scleroderma pattern on nailfold capillaroscopy, diffusion capacity of carbon monoxide in the lungs (DLCO) <70% predicted, interstitial lung disease, thrombocytopenia, and seven serological factors. Six factors were associated with a decreased risk of SLE-PAH: malar/acute rash, hematologic disorder, renal disorder, higher Systemic Lupus Erythematosus Disease Activity Index score, and two serological factors. Among these, there were six risk factors on which the panelists reached strong or general consensus (peak tricuspid regurgitation velocity on echocardiography >2.8 m/s, pericardial effusion, DLCO <70% predicted, scleroderma pattern on nailfold capillaroscopy, brain natriuretic peptide >50 ng/l, and N-terminal pro-brain natriuretic peptide >300 ng/l). The Delphi panel confirmed the need for a screening tool to identify patients with SLE at high risk of developing PAH and provided consensus on the importance and/or practicality of measuring the identified factors. CONCLUSION: The risk factors we identified could be used in a screening algorithm to identify patients with SLE with a high risk of developing PAH to facilitate early diagnosis, which could improve prognosis and management of these patients.

Economic Burden of COVID-19: A Systematic Review.

Objective: To review and qualitatively synthesize the evidence related to the economic burden of COVID-19, including healthcare resource utilization and costs. Methods: A systematic review of studies that assessed the economic burden [eg, direct costs, productivity, macroeconomic impact due to non-pharmaceutical interventions (NPIs) and equity] of COVID-19 was conducted by searches in EMBASE, MEDLINE, MEDLINE-IN-PROCESS, and The Cochrane Library, as well as manual searches of unpublished research for the period between January 2020 to February 2021. Single reviewer data extraction was confirmed independently by a second reviewer. Results: The screening process resulted in a total of 27 studies: 25 individual publications, and 2 systematic literature reviews, of narrower scopes, that fulfilled the inclusion criteria. The patients diagnosed with more severe COVID-19 were associated with higher costs. The main drivers for higher costs were consistent across countries and included ICU admission, in-hospital resource use such as mechanical ventilation, which lead to increase costs of $2082.65 ± 345.04 to $2990.76 ± 545.98. The most frequently reported indirect costs were due to productivity losses. On average, older COVID-19 patients incurred higher costs when compared to younger age groups. An estimation of a 20% COVID-19 infection rate based on a Monte Carlo simulation in the United States led to a total direct medical cost of $163.4 billion over the course of the pandemic. Conclusion: The COVID-19 pandemic has generated a considerable economic burden on patients and the general population. Preventative measures such as NPIs only have partial success in lowering the economic costs of the pandemic. Implementing additional preventative measures such as large-scale vaccination is vital in reducing direct and indirect medical costs, decreased productivity, and GDP losses.

Safety and Efficacy of Vidofludimus Calcium in Patients Hospitalized with COVID-19: A Double-Blind, Randomized, Placebo-Controlled, Phase 2 Trial.

INTRODUCTION: Vidofludimus calcium has shown anti-inflammatory effects in clinical trials of autoimmune diseases and recently demonstrated antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We performed a double-blind, randomized, placebo-controlled, phase 2 trial to evaluate the safety and efficacy of vidofludimus calcium in patients hospitalized for coronavirus disease 2019 (COVID-19) in Europe and the USA. METHODS: Patients aged 18 years or older who positive for COVID-19 were randomized (1:1) to receive placebo or 45 mg vidofludimus calcium for 14 days with both groups receiving standard-of-care treatment. The primary endpoint was the need for invasive ventilation after 28 days (ClinicalTrials.gov NCT04379271; EudraCT 2020-001264-28). RESULTS: Between June 12, 2020 and December 10, 2020, a total of 223 were randomized to receive either placebo (n = 112) or vidofludimus calcium (n = 111); three patients withdrew consent and were not treated. Eight (9%) patients in the placebo group and 12 (11%) patients in the vidofludimus calcium group needed invasive ventilation during the 28-day study period, which was lower than the assumed rate of 40%. Time to clinical improvement was shorter by approximately 1 day in the vidofludimus calcium group (15.0 days [90% CI 14.8-15.9]) compared to the placebo group (15.9 days [90% CI 14.9-19.9]). This effect was greatest in patients who initiated therapy within 9 days of symptom onset (3.8 days shorter in the vidofludimus calcium group). Higher trough concentrations of vidofludimus calcium were associated with quicker time to clinical recovery. The rate and timing of appearance of anti-SARS-CoV-2 antibodies were not different between groups. Serious adverse events occurred in 4 (4%) patients in the placebo group and 2 (2%) patients in the vidofludimus calcium group; treatment-emergent adverse events of increased severity related to COVID-19 occurred in 13 (12%) patients in the placebo group and 8 (7%) patients in the vidofludimus calcium group. Overall mortality was low (2%). CONCLUSIONS: These findings support vidofludimus calcium being safe and well tolerated in patients with COVID-19.

Burden of disease and costs associated with type 2 diabetes in emerging and established markets: systematic review analyses.

Objectives: To estimate the clinical and economic burden of type 2 diabetes (T2D) in established (EST) and emerging markets (EMG).Methods: Three systematic literature reviews were conducted in MEDLINE and Embase to capture all relevant publications reporting 1) the epidemiology of T2D and complications in T2D and 2) the economic burden of T2D and associated complications.Results: In total, 294 studies were included in this analysis. Evidence indicates a high and increasing overall prevalence of T2D globally, ranging up to 23% in EMG markets and 14% in EST markets. Undiagnosed cases were higher in EMG versus EST markets (up to 67% vs 38%), potentially due to a lack of education and disease awareness in certain regions, that could lead to important clinical and economic consequences. Poor glycemic control was associated with the development of several complications (e.g. retinopathy, cardiovascular diseases and nephropathy) that increase the risk of morbidity and mortality. Direct costs were up to 9-fold higher in patients with vs without T2D-related complications.Conclusions: The burden of T2D, related complications and inherent costs are higher in emerging versus established market countries. This review explores potential strategies to reduce costs and enhance outcomes of T2D treatment in developing countries.

New Approach toward Laser-Assisted Modification of Biocompatible Polymers Relevant to Neural Interfacing Technologies.

We report on a new approach toward a laser-assisted modification of biocompatible polydimethylsiloxane (PDMS) elastomers relevant to the fabrication of stretchable multielectrode arrays (MEAs) devices for neural interfacing technologies. These applications require high-density electrode packaging to provide a high-resolution integrating system for neural stimulation and/or recording. Medical grade PDMS elastomers are highly flexible with low Young's modulus < 1 MPa, which are similar to soft tissue (nerve, brain, muscles) among the other known biopolymers, and can easily adjust to the soft tissue curvatures. This property ensures tight contact between the electrodes and tissue and promotes intensive development of PDMS-based MEAs interfacing devices in the basic neuroscience, neural prosthetics, and hybrid bionic systems, connecting the human nervous system with electronic or robotic prostheses for restoring and treating neurological diseases. By using the UV harmonics 266 and 355 nm of Nd:YAG laser medical grade PDMS elastomer is modified by ns-laser ablation in water. A new approach of processing is proposed to (i) activate the surface and to obtain tracks with (ii) symmetric U-shaped profiles and (iii) homogeneous microstructure This technology provides miniaturization of the device and successful functionalization by electroless metallization of the tracks with platinum (Pt) without preliminary sensitization by tin (Sn) and chemical activation by palladium (Pd). As a result, platinum black layers with a cauliflower-like structure with low values of sheet resistance between 1 and 8 Ω/sq are obtained.

Surface-Enhanced Raman Spectroscopy (SERS) of Neonicotinoid Insecticide Thiacloprid Assisted by Silver and Gold Nanostructures.

This study expresses our results on surface-enhanced Raman spectroscopy (SERS) analyses of neonicotinoid insecticide thiacloprid, i.e., Calypso 480 SC, in quantities much smaller than usually applied in the agricultural medicine. Advanced Ag and Au nanostructures created by the thermal deposition technique on Al2O3 ceramic were applied as active substrates for SERS analyses. The minimum concentration of thiacloprid detected was 380 µM and the enhancement factor was estimated to be about 3 × 103. The intensity of the SERS peaks increased by an order of magnitude after pulsed laser annealing of the films and formation of nanoparticle arrays and the enhancement factor reached ≈104, respectively. The proposed study has direct bearing on the environment and human health by detection of small amounts or residue of harmful pollutants using a relatively cheap and easy method to produce active SERS substrates.

The burden of pertussis in older adults: what is the role of vaccination? A systematic literature review.

INTRODUCTION: Pertussis (whooping cough) is a vaccine-preventable disease; however, neither natural- nor vaccine-induced protection is life-long. Although generally not severe in adults, pertussis can be associated with complications in patients with chronic conditions such as asthma or chronic obstructive pulmonary disease, and can be readily transmitted to more vulnerable populations, including neonates before they complete their primary vaccination. Furthermore, as the global population ages, the health and economic burden of the disease is expected to rise. Areas covered: A systematic literature review was conducted to ascertain the current epidemiological and financial burden of pertussis in older adults and to discuss the potential value of a booster vaccination in this population. Expert commentary: Our review indicates a considerable underestimation of the pertussis burden amongst older adults. Seroprevalence studies consistently demonstrate that the reported incidence may be much lower than the actual incidence. Tetanus toxoid-reduced diphtheria toxoid and acellular pertussis vaccines are immunogenic in older adults, induce high booster responses and are well-tolerated. There is therefore a good rationale for the advocacy of booster pertussis vaccination throughout life to prevent pertussis infection and its transmission, especially in adults aged ≥50 years.