Life Expectancy Of Patients Research Articles

Equitable Care for Severe Hemophilia_A: Distributional Cost-Effectiveness of Prophylactic Weekly Efanesoctocog Alfa Versus Standard-Care Factor VIII in Patients with Severe Hemophilia_A in the United States

Introduction: Prophylactic coagulation factor replacement is crucial to decrease bleeding episodes and improve quality-adjusted life expectancy (QALE) for patients with severe hemophilia A. Even with prophylactic treatment (i.e., at three to four times weekly) patients remain at risk of bleeding events and still develop chronic arthropathy across their lifetimes. The additional economic burden associated with lifelong prophylactic treatment is a major equity concern for patients with hemophilia A and their families. Efanesoctocog alfa is a recently developed extended half-life agent for hemophilia A prophylaxis and management, supporting the possibility of once-weekly prophylaxis. An open-label multicenter study (XTEND-1) showed that once-weekly dosing of efanesoctocog alfa improves the annualized bleeding rate (ABR) by 77% versus prophylaxis with standard-care factor VIII in patients with severe hemophilia A. We sought to evaluate, both for the first time, the conventional and distributional cost-effectiveness of prophylaxis with efanesoctocog alfa versus with standard-care factor VIII for patients with severe hemophilia A in the United States. Methods: For this independent analysis free of industry influence, we built a Markov model to examine the conventional cost-effectiveness of prophylaxis with efanesoctocog alfa versus standard-care factor VIII for patients with severe hemophilia A. Transition probabilities for ABRs and product utilization were informed by phase 3 study data and supplemented with FDA package insert information. Within ABRs, we accounted for treated bleeding severity and bleeding event types, inclusive of hemarthrosis, intracranial hemorrhage, in addition to assuming the prevalence of chronic arthropathy with SHL (i.e., due to silent bleed burden) is eliminated by efanesoctocog alfa. Costs for the base-case were sourced from the Centers for Medicare & Medicaid Services with negotiated (i.e., lower) cost of efanesoctocog alfa supplied from the Veterans Affairs Federal Supply Schedule Service (VA-FSS). Age-, sex- and disease-specific background mortality were employed. Utilities for severe hemophilia A and disutilities for bleed events and hospitalizations were informed by extensive literature specific to severe hemophilia A. The primary outcome was the incremental cost-effectiveness ratio (ICER) in USD/QALY, at a willingness-to-pay threshold of $150,000/quality-adjusted life-year (QALY). The secondary outcome was a threshold analysis for the maximum efanesoctocog alfa price that renders efanesoctocog alfa prophylaxis cost-effective. To account for health inequities in the care of patients with hemophilia A we then conducted a distributional cost-effectiveness analysis (DCEA) to derive an equity weight threshold (i.e., inequality aversion parameter) for the decision of prophylaxis with efanesoctocog alfa versus with standard-care factor VIII. This threshold was then compared to prior estimates for commonly used equity weights in the United States (range 0.5-3.0). Results: In the base-case, prophylaxis with efanesoctocog alfa versus with standard-care factor VIII accrued 19.4 and 15.4 QALYs at mean costs of $17.3 and $9.7 million. The ICER for efanesoctocog alfa was $1,890,000/QALY (95% credible interval 1,190,000-3,330,000). Threshold analysis showed that prophylaxis with efanesoctocog alfa became cost-effective when the price of efanesoctocog alfa decreased by at least 59%. In deterministic sensitivity analysis, the model was most sensitive to the costs of efanesoctocog alfa and factor VIII. In probabilistic sensitivity analysis, standard-care factor VIII was favored over efanesoctocog alfa in 100% of 10,000 Monte Carlo simulations. The equity weight threshold for the treatment decision of prophylaxis with efanesoctocotog alfa versus with standard-care factor VIII was 7.4, higher than commonly used equity weights in the US. This implies a threshold that is higher than what has previously been used in the United States, per DCEA standards. Conclusion: As compared to standard-care factor VIII and at VA-FSS pricing, efanesoctocog alfa prophylaxis is conventionally cost-ineffective for patients with severe hemophilia A. Prophylaxis with efanesoctocog alfa does not meet commonly used distributive equity standards in the United States at this time.

Snake Oil or Super Drug: How Have Regulators and Payers Perceived New Medicines that Target Asymptomatic Conditions?

Context: Assess how relevant precedent within the European Medicines Agency (EMA) (a key regulator) and the National Institute for Health and Care Excellence (NICE) (a key health technology assessment (HTA) body) can provide insights into how such novel medicines targeting asymptomatic conditions can be brought to market from both a regulatory and payer perspective.
 Methods: All phase 2 or phase 3 clinical trials with keywords such as asymptomatic, pre-symptomatic, subclinical, premanifest, or preclinical keywords were downloaded from clinicaltrials.gov. Trials were cleaned to identify those for novel medicines with a primary focus on treating asymptomatic conditions. The EMA and NICE report for such drugs were downloaded online in December 2021 and analyzed to understand how they assessed the evidence.
 Results: Two hundred seventy-eight clinical trials were identified. Of those, only 8 had relevant matching reports from the EMA or NICE, 7 received a positive review from the EMA, and 4 received a positive recommendation from the NICE. Those who received positive recommendations showed or were assumed to show statistically significant survival benefits given the short life expectancy of untreated patients.
 Conclusions: There is no precedent within the EMA or NICE for approving or funding new medicines for asymptomatic patients where survival benefits cannot be established. Additional research is warranted to understand how regulatory and payer agencies can prepare for future generations of innovative medicines.

Incidence of Second Primary Malignancies in Medicare-Insured Patients in the US with Triple-Class Exposed Relapsed/Refractory Multiple Myeloma

Background As therapeutic advances have increased life expectancy for patients (pts) with relapsed/refractory (RR) multiple myeloma (MM), second primary malignancies (SPMs) have become an increasingly important safety consideration. Prior studies have demonstrated that treatment with alkylators, autologous stem cell transplantation, and immunomodulatory drugs (IMiDs), specifically lenalidomide, are associated with increased risk of SPM. Pts who are triple-class exposed (TCE), defined as prior exposure to an IMiD, a proteasome inhibitor (PI), and an anti-CD38 monoclonal antibody (mAb), represent an increasingly large subgroup of RRMM pts. The objective of this study was to describe the incidence and characteristics of SPMs in Medicare-insured pts with TCE RRMM initiating a new line of therapy (LOT). Methods Adult pts with an incident diagnosis (Dx) of MM (≥2 outpatient Dx 30-365 days apart OR ≥1 inpatient Dx AND 6 months of continuous eligibility prior to initial Dx) during the study period (Nov 14, 2006-Dec 31, 2020) who were TCE (≥1 claim each for an IMiD, a PI, and an anti-CD38 mAb) were selected from the Center for Medicare and Medicaid Services Chronic Conditions Data Warehouse (TCE pts were assumed to have RRMM based on exposure). The first LOT after TCE was defined as the index LOT and the associated date of initiation was defined as the index date. Pts with SPMs prior to the index date were excluded. SPMs were identified based on having ≥2 outpatient Dx of SPM (of the same cancer type) 30-365 days apart OR ≥1 inpatient Dx of SPM. Dx of SPM included Dx of invasive malignancies or myelodysplastic syndromes (MDS), excluding MM, Waldenström macroglobulinemia, plasma cell leukemia, non-melanoma skin cancers, or primary bone malignancies that were preceded by a Dx of bone metastases. The incidence of SPM was calculated per 100 person years (PY) of follow-up, considering only the first SPM for each pt. Cumulative incidence of SPM (with death as a competing risk) was also calculated. For pts who experienced SPM, overall survival (OS) and measures of healthcare resource utilization (HRU) and costs (in 2021 USD, on a per patient per month [PPPM] basis) were calculated. Results A total of 3,088 TCE RRMM pts were identified, of whom 989 had no evidence of SPM prior to the index date (Table). These 989 pts had a mean age of 75.2 years, a mean of 2.9 prior LOTs and a mean of 3.1 years since MM Dx. Over a median follow-up of 7.1 months, 166 pts (19.3 per 100 PY) experienced an SPM, including 93 (10.8 per 100 PY) with a solid tumor and 73 (8.5 per 100 PY) with a hematologic malignancy. The latter included 27 (3.1 per 100 PY) with acute myeloid leukemia (AML) and 18 (2.1 per 100 PY) with MDS. The cumulative incidence of SPM (95% confidence interval [CI]) at 12, 24, and 36 months was 15.2% (12.8-17.9%), 19.7% (16.8-22.8%), and 23.8% (20.2-27.6%), respectively (Figure). Median (95% CI) OS from SPM Dx was 7.9 months (5.4-10.9). Kaplan-Meier estimated probability of survival (95% CI) at 12, 24, and 36 months following SPM Dx was 40.3% (31.6-48.9%), 27.6% (18.6-37.4%), and 9.5% (2.1-23.8%), respectively. Mean (95% CI) total costs after SPM were $22,514 ($19,105-$26,404) PPPM. Conclusions The incidence of SPM in Medicare-insured TCE RRMM pts is high. Many SPMs in these pts, such as AML, are life-threatening and may interfere with or prevent MM treatment. Pts with SPMs have poor survival and high HRU and costs. With increasing OS for RRMM pts due to therapeutic advancements, there is a need for effective treatments that are not associated with increased risk of SPMs.

Longitudinal Systemic Bevacizumab Therapy Produces Cost Savings and Improves Quality-Adjusted Life Expectancy in the Care of Patients with Hereditary Hemorrhagic Telangiectasia with Moderate-to-Severe Bleeding

Introduction: Hereditary hemorrhagic telangiectasia (HHT) is the second-most-common hereditary bleeding disorder worldwide, afflicting 1 in 5000 or 1.4 million persons. Unlike peer disorders hemophilia and von Willebrand disease, there are no FDA or EMA-approved therapies. The current standard-of-care (SOC) consists of red blood cell (RBC) transfusion, IV iron supplementation, and local hemostatic procedures (i.e., nasal, gastrointestinal). However, bleeding pathophysiology is amenable to vascular endothelial growth factor inhibition, and IV bevacizumab has shown great promise as a disease-modifying therapeutic. The multisite, international InHIBIT-Bleed study employed a pre- versus post-bevacizumab design and was the largest clinical study of HHT (n=238). InHIBIT-Bleed demonstrated that longitudinal systemic bevacizumab significantly improved clinical symptoms, raised hemoglobin levels, and nearly abrogated IV iron infusion and RBC transfusion need for patients with HHT. Although bevacizumab is an expensive biologic agent with a financial barrier to access, we hypothesized that reduction in health resource utilization and improvement in transfusion dependence will improve quality-of-life for patients with HHT at costs commensurate with added clinical value. Accordingly, we conducted the first cost-effectiveness analysis of bevacizumab therapy in HHT. Methods: For this independent analysis free of industry influence, we built a Markov simulation of adult patients with HHT to examine the cost-effectiveness of bevacizumab added to SOC versus SOC alone, over a lifetime time-horizon and across accepted willingness-to-pay (WTP) thresholds. Costs were assessed in 2023 US dollars. We employed study data for pre- and post-bevacizumab that included descriptive statistics for 1) hemostatic procedures, 2) hospitalizations, 3) emergency department visits, 4) RBC transfusions, and 5) iron infusions. Treatment-specific patient time and lost wages were also accounted for across IV infusions, emergency department visits, hospitalizations, and hemostatic procedures. Probabilities of RBC- and iron-related adverse events were sourced from hemovigilance reports, the 2015 National Blood Collection and Utilization Survey and 2008-2017 World Health Organization's VigiBase. Ferric carboxymaltose was used as the base-case iron supplement, and a scenario analysis examined ferumoxytol. Effectiveness was calculated in QALYs, and employed age-adjusted utilities derived using HHT-specific EQ-5D index values, with the 2019 Global Burden of Disease Study used to account for the degree of anemia improvement reported with bevacizumab. The primary outcome was the incremental cost-effectiveness ratio (ICER), or incremental net monetary benefit (iNMB) if intervention was found to be cost-saving. The secondary outcome was the aggregated patient time spent receiving HHT-specific care. We concluded by conducting deterministic and probabilistic sensitivity analyses, capturing uncertainty in all parameters simultaneously over 10,000 Monte Carlo iterations. Results: In the base-case, bevacizumab versus SOC cost $959,000 and $1,533,000 while accruing 24.1 and 21.8 QALYs, respectively. The iNMB with bevacizumab was $916,000 [95% credible interval $454,000-$1,994,000] and $1,004,000 [95% CI $473,000-$2,237,000] from the US health system and societal perspectives, respectively, at a WTP of $150,000/QALY. Bevacizumab also saves patients 125 hours per year lived. Deterministic sensitivity analysis revealed that no parameter variance changes the model result. In probabilistic sensitivity analysis bevacizumab was favored in 100.0% of 10,000 Monte Carlo iterations: saving cost with increased QALYs in 99.6% and cost-effective in the remaining 0.4% of iterations (Figure 1). Similar cost-savings were found in the scenario analysis with ferumoxytol. Conclusion: By reducing the need for hemostatic procedures, hospitalizations, emergency visits, RBC transfusions, and iron infusions, bevacizumab is, unusually, a cost-saving intervention that also improves the quality-adjusted life expectancy of patients with HHT. Bevacizumab also saves patient time spent on receiving HHT-specific care. Collecting long-term follow-up data to evaluate continued response to bevacizumab will help assess its value versus future advances in the care of patients with HHT.

Photodynamic therapy of malignant brain tumors (literature review

Primary brain malignancies are among the 17 most common tumor types worldwide, and about 77 % of them are glial tumors. An integrated approach to the treatment of these pathologies, including total resection of tumor tissue and postoperative chemotherapy and radiation therapy, is aimed at prolonging the patient’s life as much as possible. However, even when using the «gold standard» in treatment, the average life expectancy of patients with glioblastoma is 14.6 months, and of patients with diffuse astrocytoma — 50.5 months. The use of selective methods of influencing tumor cells, including photodynamic therapy, is a current trend in neuro-oncology. Several controlled studies have demonstrated a statistically significant effect of photodynamic therapy in increasing the life expectancy of patients with high-grade gliomas compared with conventional treatment. This review is devoted to the analysis of the effectiveness of photodynamic therapy and fluorescence-guided resection in the treatment of high-grade glial tumors for further search for ways to improve these treatment methods in order to enhance the radicality of tumor removal and increase the duration and quality of life of patients.

The Association between Levels of Physical Activity and Lifestyle, Life Expectancy, and Quality of Life in Patients with Alzheimer’s Disease

Background: Engaging in physical activity could help improve the quality of life in patients with Alzheimer’s disease. The objective of this study was to determine the association between the levels of physical activity and lifestyle, life expectancy, and quality of life in patients with Alzheimer’s disease in Iran and Italy. Methods: A total of 165 participants from Iran and Italy were enrolled in this cross-sectional study. In Iran, 85 patients participated in the study. In Italy, we enrolled 80 patients at the Sapienza University teaching hospital, Policlinico Umberto 1 in Rome. The inclusion criteria in this study include patients over 60 years old, non-smokers, and non-users of antidepressants and hypnotics. Results: The results of Tukey’s post hoc test of the study conducted in Iran showed that the lifestyle of patients with moderate (p = 0.001) and low (p = 0.009) physical activity levels was significantly better than inactive patients. Life expectancy in patients with moderate physical activity levels was significantly higher than inactive patients (p = 0.011). The quality of life was significantly better in patients with moderate (p = 0.001) and low (p = 0.002) physical activity levels than inactive patients. On the other hand, the findings of Tukey’s post hoc test of the study in Italy showed that the quality of life in patients with low (p = 0.001) and moderate physical activity levels (p = 0.01) was significantly higher than inactive patients. Conclusions: A low to moderate level of physical activity could be associated with an improved lifestyle, life expectancy, and quality of life in patients with Alzheimer’s disease compared to inactivity.

A randomised phase 2 study of intermittent versus continuous dosing of dabrafenib plus trametinib in patients with BRAFV600 mutant advanced melanoma (INTERIM)

BackgroundBRAF+MEK inhibitors extend life expectancy of patients with BRAFV600 mutant advanced melanoma. Acquired resistance limits duration of benefit, but preclinical and case studies suggest intermittent dosing could overcome this limitation. INTERIM was a phase 2 trial evaluating an intermittent dosing regimen. MethodsPatients with BRAFV600 mutant advanced melanoma due to start dabrafenib+trametinib were randomised to receive either continuous (CONT), or intermittent (INT; dabrafenib d1–21, trametinib d1–14 every 28 days) dosing. A composite primary endpoint included progression-free survival (PFS) and quality of life (QoL). Secondary endpoints included response rate (ORR), overall survival (OS) and adverse events (AEs). Mutant BRAFV600E ctDNA was measured by droplet digital PCR (ddPCR), using mutant allele frequency of > 1 % as the detection threshold. Results79 patients (39 INT, 40 CONT) were recruited; median age 67 years, 65 % AJCC (7th ed) stage IV M1c, 29 % had brain metastases. With 19 months median follow-up, INT was inferior in all efficacy measures: median PFS 8.5 vs 10.7mo (HR 1.39, 95 %CI 0.79–2.45, p = 0.255); median OS 18.1mo vs not reached (HR 1.69, 95 %CI 0.87–3.28, p = 0.121), ORR 57 % vs 77 %. INT patients experienced fewer treatment-related AEs (76 % vs 88 %), but more grade > 3 AEs (53 % vs 42 %). QoL favoured CONT. Detection of BRAFV600E ctDNA prior to treatment correlated with worse OS (HR 2.55, 95 %CI 1.25–5.21, p = 0.01) in both arms. A change to undetected during treatment did not significantly predict better OS. ConclusionINTERIM findings are consistent with other recent clinical trials reporting that intermittent dosing does not improve efficacy of BRAF+MEK inhibitors.

Resultados tras 5 años de cirugía o abordaje percutáneo en coronariopatía grave. Metanálisis de ensayos aleatorizados con reconstrucción del tiempo hasta el evento

Introduction and objectivesThere is controversy about the optimal revascularization strategy in severe coronary artery disease (CAD), including left main disease and/or multivessel disease. Several meta-analyses have analyzed the results at 5-year follow-up but there are no results after the fifth year. We conducted a systematic review and meta-analysis of randomized clinical trials, comparing results after the fifth year, between coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) using drug-eluting stents in patients with severe CAD. MethodsWe analyzed all clinical trials between January 2010 and January 2023. The primary endpoint was all-cause mortality. The databases of the original articles were reconstructed from Kaplan-Meier curves, simulating an individual-level meta-analysis. Comparisons were made at certain cutoff points (5 and 10 years). The 10-year restricted median survival time difference between CABG and PCI was calculated. The random effects model and the DerSimonian-Laird method were applied. ResultsThe meta-analysis included 5180 patients. During the 10-year follow-up, PCI showed a higher overall incidence of all-cause mortality (HR, 1.19; 95%CI, 1.04-1.32; P=.008)]. PCI showed an increased risk of all-cause mortality within 5 years (HR, 1.2; 95%CI, 1.06-1.53; P=.008), while no differences in the 5–10-year period were revealed (HR, 1.03; 95%CI, 0.84-1.26; P=.76). Life expectancy of CABG patients was slightly higher than that of PCI patients (2.4 months more). ConclusionsIn patients with severe CAD, including left main disease and/or multivessel disease, there was higher a incidence of all-cause mortality after PCI compared with CABG at 10 years of follow-up. Specifically, PCI has higher mortality during the first 5 years and comparable risk beyond 5 years.

Cytogenetic and Molecular Remission in Chronic Myeloid Leukemia in Togo

The availability of tyrosine kinase inhibitors (TKIs) in Togo through the GIPAP program has revolutionized the management of chronic myeloid leukemia and increased patient life expectancy. However, diagnosis and molecular monitoring of therapeutic efficacy remain a real challenge due to the inaccessibility of cytogenetic and molecular biology tools. We’ve conducted, a cross-sectional, descriptive study that ran from December 21, 2022, to January 20, 2023, with the aim to evaluate the cytogenetic and molecular remission in CML patients followed at the CHU Campus de Lomé in Togo. Patients diagnosed with chronic-phase CML who had been treated for at least three months with imatinib or dasatinib and had achieved complete hematological remission were included. Dosage of BCR-ABL transcript levels was performed by RQ-PCR in Seattle, USA, using Dried Blood Spot. The transcript detection limit was 0.003% i.e., MR4. A total of 38 patients were included, 68.4% of them were treated with imatinib and 31.6% with dasatinib. In terms of remission, 28.9% had not achieve a partial cytogenetic remission while 15.8% of patients had achieved a MR4 remission and 7.9% a major molecular remission. Major molecular remission was achieved at a mean follow-up time of 95 months for patients taking imatinib and 22 months for those taking dasatinib. Patients in MR4 were on imatinib after a mean of 68 months. All in one, our study showed a high rate of treatment failure. Better access to cytogenetic and molecular biology tools is needed to improve management.

OGBN P15 The cost-effectiveness of a novel implantable device for treating gastro-oesophageal reflux disease in the United Kingdom

Abstract Background Gastro-oesophageal reflux disease (GORD) is a common gastrointestinal condition characterized by heartburn, chest pain, and regurgitation. Chronic treatment with proton pump inhibitor (PPI)-based medical management is the current standard of care, with antireflux surgery considered in selected patients. RefluxStop is a novel implantable device indicated for patients eligible for laparoscopic anti-reflux surgery. The purpose of this analysis was to assess the cost-effectiveness of RefluxStop against other GORD treatment options in the UK. Methods A Markov model was developed to assess the cost-effectiveness of RefluxStop compared with PPI-based medical management, laparoscopic Nissen fundoplication, and magnetic sphincter augmentation (MSA) for management of GORD. The UK National Health Service perspective was adopted, with clinical outcomes and costs estimated over a lifetime horizon and an annual discount rate of 3.5% applied. Clinical efficacy data for RefluxStop was obtained from its CE mark study, and comparator treatments were based on published literature. Results RefluxStop demonstrated favorable surgical outcomes compared to both laparoscopic Nissen fundoplication and MSA. The base case incremental cost-effectiveness ratios (ICERs) compared with PPIs, laparoscopic Nissen fundoplication, and MSA were £4,156, £6,517, and £249 per quality-adjusted life-year (QALY) gained, respectively. With a UK cost-effectiveness threshold of £20,000 per QALY gained, the probabilities that RefluxStop was cost-effective compared with PPIs, laparoscopic Nissen fundoplication, and MSA were 100%, 93%, and 100%, respectively. Conclusions Based on this analysis, RefluxStop was estimated to improve quality of life and extend life expectancy in GORD patients when compared to PPIs, laparoscopic Nissen fundoplication, and MSA. Furthermore, this analysis demonstrated that RefluxStop is highly likely to be a cost-effective option for treating GORD in the UK.

Characteristics of CF patients over 18 years of age in the Republic of Tatarstan

Introduction. Cystic fibrosis is a hereditary disease characterized by the defeat of all exocrine glands, vital organs and systems. Currently, the life expectancy of patients with cystic fibrosis is increasing due to the development of new therapies.Goal. Analysis of the results of a comprehensive examination of patients with cystic fibrosis under the supervision of a pulmonologist of Republican Clinical Hospital (RCH) of the Ministry of Health of the Republic of Tatarstan.Materials and methods. The analysis of the database of patients with cystic fibrosis, older than 18 years, registered in the Regional Center of cystic fibrosis of the Republic of Tatarstan (RT).Results. As of April 2023, 47 patients over the age of 18 with a diagnosis of cystic fibrosis were registered in the RCH of the Ministry of Health of the Republic of Tatarstan. The diagnosis was made on the basis of a positive sweat sample and/or a genetic study. The age of patients is from 18 to 39 years (26.1 ± 1.1 years). Women – 49%, men – 51%. Median body weight – 51.5 kg, height – 165 cm, BMI – 18.05 kg/m2. 25 patients (53.2%) had a BMI of less than 18.5 kg/m2. Among patients in RT, the most common mutation is F508del. When assessing the microbiological profile of the respiratory tract, chronic infection was detected in 37 patients (78.7%). Ps. aeruginosa (66.0%) and S.aureus (35.6%) were the most frequently sown. The average FVC indicators were 72.6 ± 4.3% predicted values, the average FEV1 indicators were 61.6 ± 28.1% predicted values.Conclusion. On the territory of the Republic of Tatarstan in patients with cystic fibrosis, the F508del mutation was detected in 30 (66.7%) adult patients, 9 of whom receive targeted therapy elecsacaftor / tezacaftor / ivacaftor+ ivacaftor with a pronounced positive effect. The high incidence of P. aeruginosa infection (66.0%) and a decrease in respiratory function among adult patients indicate a more severe course of cystic fibrosis.

Clinical Update of Thermal Burns Injury

The initial 48 hours following a thermal burn injury present the most significant window of opportunity to influence a patient's life expectancy. This review was aimed to describe clinical update of thermal burn injury. Burns are categorized according to their size, severity, the age of the patient, and any related medical conditions or injuries. A precise assessment of the magnitude and extent of the burn injury is essential for quantifying resuscitation parameters. Smoke inhalation, trauma, and electrical injuries are frequently present with burns. Severe burns, regardless of their origin, can lead to comparable complications such as infection, difficulty breathing, dysfunction of multiple organs, blood clot formation in veins, and gastrointestinal issues. In conclusion, the treatment plan of thermal burns will be determined based on the expected location, size, and depth of the burn. The initial 48 hours of burn care have the most significant influence on the morbidity and death of burn victims.

Diagnostic problems in pediatrics on the example of a clinical case of neuroblastoma

Neuroblastoma (NB) is a malignant extracranial solid tumor of childhood. The peak incidence occurs in the first year of life. In 50% of cases, the disease already has signs of metastasis at the time of diagnosis. The clinical picture in neuroblastoma is varied; the symptoms are not specific and depend on the localization. The diagnosis is confirmed by histological examination of the biopsy of the primary tumor and metastasis. A specific method for the topical diagnosis of neuroblastoma is 123I-labeled metaiodobenzylguanidine scintigraphy, which makes it possible to detect the primary tumor, the presence of regional and distant metastases. Combinations of high-dose chemotherapy and transplantation of autologous stem cells and differentiating agents, as well as immunotherapy with anti-GD2 monoclonal antibodies, can increase the life expectancy of patients.

The practical significance of using Canephron N medication for radiation cystitis prevention in patients undergoing radiation/chemoradiation therapy

Background. With increasing life expectancy in cervical cancer patients, new medical and social problems associated with radiation therapy become apparent. The combination of radiation therapy and chemotherapy is an important therapeutic component in treatment of malignant neoplasms of the genital area in women, but the frequency and severity of side effects has been increasing. Radiation complications occur in 20–50 % of patients. In 5 % of patients, they can represent a severe and potentially life-threatening condition. Prevention of negative effects on the genitourinary system in cervical cancer patients receiving radiation therapy on the pelvis is a matter of importance.Aim. To evaluate the clinical efficacy of a phytotherapeutic preparation Canephron N containing centaury, lovage root, rosemary leaves in the prevention of radiation cystitis during chemoradiotherapy in patients with advanced cervical cancer.Materials and methods. The study included 60 patients with locally advanced cervical cancer receiving radical chemoradiotherapy. The patients were divided into 2 groups: treatment group consisting of patients receiving phytotherapeutic preparation Canephron N for prevention of radiation complications, and control group consisting of patients not receiving symptomatic treatment. The treatment results were evaluated using questionnaires, clinical, laboratory and instrumental studies. The obtained data were compared with the results of treatment of the control group which were not prescribed a medication for prevention of urological complications.Results and conclusion. The use of Canephron N in accompanying therapy had significantly decreased the risk and incidence of radiation cystitis.

A new fluorescent probe for the visualization of progerin

Hutchinson-Gilford progeria syndrome (HGPS) or progeria is a rare genetic disease that causes premature aging, leading to a drastic reduction in the life expectancy of patients. Progeria is mainly caused by the intracellular accumulation of a defective protein called progerin, generated from a mutation in the LMNA gene. Currently, there is only one approved drug for the treatment of progeria, which has limited efficacy. It is believed that progerin levels are the most important biomarker related to the severity of the disease. However, there is a lack of effective tools to directly visualize progerin in the native cellular models, since the commercially available antibodies are not well suited for the direct visualization of progerin in cells from the mouse model of the disease. In this context, an alternative option for the visualization of a protein relies on the use of fluorescent chemical probes, molecules with affinity and specificity towards a protein. In this work we report the synthesis and characterization of a new fluorescent probe (UCM-23079) that allows for the direct visualization of progerin in cells from the most widely used progeroid mouse model. Thus, UCM-23079 is a new tool compound that could help prioritize potential preclinical therapies towards the final goal of finding a definitive cure for progeria.

MODL-35. BIOENGINEERED HYDROGEL AND BLOOD BRAIN BARRIER-ON-A-CHIP SYSTEM TO STUDY GLIAL CELL ACTIVATION AND BLOOD BRAIN BARRIER DYSFUNCTION IN GLIOBLASTOMA

Abstract Treatments for glioblastoma (GBM) are limited leading to short patient life expectancies after diagnosis. Current preclinical models of GBM fail to accurately replicate the function of the blood brain barrier (BBB) and the extreme heterogeneity of the GBM tumor hindering the drug development process. Therefore, there is a pressing need for improved model systems to study how different GBM subpopulations interact with glial cells and the BBB. To build such a model, we first focused on designing a 3D extracellular matrix-based hydrogel biomaterial that would support human astrocytes and a functional BBB. The hydrogel chosen for these studies is composed of functionalized hyaluronic acid (HA) and gelatin and has similar mechanical properties to the human brain. Using confocal imaging and qPCR, we have shown that astrocytes encapsulated in this hydrogel have greater branching and express fewer markers of activation compared to astrocytes grown in commonly used 3D biomaterials such as collagen I and Matrigel. Treatment with inflammatory cytokines and GBM cell derived extracellular vesicles (EVs) revealed that astrocytes in this environment display the activation and inflammatory phenotypes observed in vivo in GBM. Next, this hydrogel biomaterial was deployed in a bioengineered BBB-on-a-chip. We have shown that this system supports the formation of 3D microvessel structures with human brain endothelial cells, pericytes, and astrocytes that accurately mimic the function of the human BBB. Studies using this BBB-on-a-chip have shown that invasive glioma stem cells alter BBB permeability influencing the transport of certain therapeutics to the tumor site. We are now beginning to test how various subpopulations of GBM tumor cells behave in this model and how changes to glial cells and the BBB impact drug delivery and efficacy. This study shows that engineered in vitro models can provide critical insight into disease mechanisms and inform treatment design in GBM.

The effectiveness of high-intensity interval training compared to moderate-intensity continuous training in patients with heart failure: a systematic review and meta-analysis

Abstract Background/Introduction Cardiac rehabilitation including exercise therapy is beneficial for improving exercise tolerance, physical function, quality of life (QOL), and life expectancy in patients with heart failure. High-intensity interval training (HIIT) has attracted attention as a new training modality in heart failure, whereas moderate-intensity continuous aerobic training (MCT) is recommended as the main training modality to improve exercise tolerance. However, the effects of HIIT in patients with heart failure remain controversial. Purpose This systematic review and meta-analysis aimed to examine the effectiveness of HIIT compared to MCT on exercise tolerance in patients with heart failure. Methods We searched for studies published up to 4 March 2022 in EMBASE, MEDLINE via Ovid SP, PubMed, and the Cochrane Library via Wiley Online Library with no limitations on data, language, or publication status. We included randomised controlled trials comparing the effectiveness of HIIT and MCT on peak oxygen uptake (VO2), as a measure of exercise tolerance, aerobic threshold (AT) VO2, ventilatory equivalent of carbon dioxide (VE/VCO2), and QOL. We pooled the data on peak VO2, compared HIIT to MCT, and conducted a sub-analysis if there was heterogeneity in the result. Results We identified 15 randomised controlled trials with 557 patients from a total of 23,272 records. Our meta-analysis showed that participants who underwent HIIT achieved a significantly higher peak VO2 than those who underwent MCT (mean difference 1.46 ml/kg/min, 95% confidence interval 0.39 to 2.53; I2 = 65.7%; very low-quality evidence) (Figure 1). Participants who underwent HIIT had no statistically significant difference in AT VO2, VE/VCO2, and QOL compared to those who underwent MCT. The meta-regression analysis, conducted as a sub-analysis to explore possible causes of heterogeneity, revealed that the effect size of HIIT compared to MCT was inversely associated with body mass index (r = -0.508, p = 0.028, 95% confidence interval -0.95 to -0.07) (Figure 2). Conclusions Our systematic review showed that HIIT achieved a higher peak VO2 than MCT in patients with heart failure. In addition, HIIT may be more effective in improving exercise tolerance in patients with low body mass index.

Frailty phenotype and cognitive functioning in middle-aged and older adults with congenital heart disease: results of an international multicentric study

Abstract Background The life expectancy of patients with congenital heart disease (CHD) has increased rapidly, resulting in a growing and aging population. Recent studies showed that older CHD patients have a higher morbidity, healthcare utilization, and mortality. Furthermore, many will encounter a state of frailty. To maintain longevity and quality of life, understanding the evolving medical and psychosocial challenges of older patients is important to enable the mapping of specific healthcare needs. There are indications that, independent of age and comorbidity, the frailty phenotype can guide risk prediction in chronically ill patients. However, current knowledge on frailty phenotype and cognitive function of older CHD patients is limited. Purpose This study aimed (i) to describe the frailty and cognitive profile of older adults with mild to complex CHD, and (ii) to investigate the relationship with patient-related factors (e.g., age, complexity of CHD and physiological stage). Methods Using a cross-sectional, multicentric design, we included 814 patients aged ≥ 40 years (median age: 52y [45.0-61.0]; 52% women; 13% mild, 70% moderate, 17% complex CHD) from 17 centers in 11 countries. The frailty phenotype was determined using the Fried method, which classifies patients as robust, prefrail and frail based on five criteria: weakness; slow walking speed; unintentional weight loss; exhaustion; and low physical activity. Cognitive function was evaluated using the Montréal Cognitive Assessment (MoCA). Comorbidities were assessed using the Charlson Comorbidity Index (CCI). Results In this sample, 52% of patients were assessed as robust, 42% prefrail, and 6% frail. Based on the MoCA, 39% had cognitive dysfunction. A weak negative correlation was found between frailty and cognitive functioning (rho=-0.210, p<0.001). Multinomial regression showed that prefrail and frail status was associated with older age, female sex, higher physiological class, and comorbidities (Table 1). Logistic regression demonstrated that cognitive dysfunction was related to older age and comorbidities. Conclusion Approximately half of the sample of CHD patients were (pre)frail and almost two out of five experienced cognitive impairment. These age-related problems were not related to the anatomical complexity of the heart condition, indicating that these issues are not limited to severe CHD. Future research is needed to determine the impact of these findings on healthcare use.

Synthesis of Multifunctional Mn3O4-Ag2S Janus Nanoparticles for Enhanced T1-Magnetic Resonance Imaging and Photo-Induced Tumor Therapy.

The global burden of cancer is increasing rapidly, and nanomedicine offers promising prospects for enhancing the life expectancy of cancer patients. Janus nanoparticles (JNPs) have garnered considerable attention due to their asymmetric geometry, enabling multifunctionality in drug delivery and theranostics. However, achieving precise control over the self-assembly of JNPs in solution at the nanoscale level poses significant challenges. Herein, a low-temperature reversed-phase microemulsion system was used to obtain homogenous Mn3O4-Ag2S JNPs, which showed significant potential in cancer theranostics. Structural characterization revealed that the Ag2S (5-10 nm) part was uniformly deposited on a specific surface of Mn3O4 to form a Mn3O4-Ag2S Janus morphology. Compared to the single-component Mn3O4 and Ag2S particles, the fabricated Mn3O4-Ag2S JNPs exhibited satisfactory biocompatibility and therapeutic performance. Novel diagnostic and therapeutic nanoplatforms can be guided using the magnetic component in JNPs, which is revealed as an excellent T1 contrast enhancement agent in magnetic resonance imaging (MRI) with multiple functions, such as photo-induced regulation of the tumor microenvironment via producing reactive oxygen species and second near-infrared region (NIR-II) photothermal excitation for in vitro tumor-killing effects. The prime antibacterial and promising theranostics results demonstrate the extensive potential of the designed photo-responsive Mn3O4-Ag2S JNPs for biomedical applications.

Estimation of life expectancy and healthcare cost in rheumatoid arthritis patients with and without depression: a population-based retrospective cohort study.

This study aimed to estimate the lifetime healthcare costs and loss of life expectancy (loss-of-LE) among patients with incident rheumatoid arthritis (RA) with and without depression. This 18 years longitudinal cohort study used data from Taiwan's National Health Insurance Research Database. In total, 43,311 patients with RA were included. Among them, 1,663 patients had depressive disorders in the year preceding the RA diagnosis. The survival function for patients with RA with or without depression was estimated and extrapolated over a lifetime using the rolling extrapolation algorithm. The loss-of-LE was calculated by comparing the sex, age, and calendar year-matched referents from vital statistics. The average monthly cost was calculated as the sum of the monthly costs for all patients divided by the number of surviving patients. Lifetime healthcare costs were estimated by multiplying the monthly average cost by the monthly survival probability. The loss-of-LE for RA patients with and without depression was 5.60 years and 4.76 years, respectively. The lifetime costs of RA patients with and without depression were USD$ 90,346 and USD$ 92,239, respectively. However, the annual healthcare costs were USD$ 4,123 for RA patients with depression and USD$ 3,812 for RA patients without depression. Regardless of sex or age, RA patients with depression had higher annual healthcare costs than those without depression. Patients with RA and depression have a high loss-of-LE and high annual healthcare costs. Whether treating depression prolongs life expectancy and reduces healthcare costs warrants further investigation.