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The vertical distribution and stoichiometry characteristics of soil organic carbon (SOC), total nitrogen (TN), total phosphorus (TP) of soil profiles along an altitude gradient were investigated in Luofu Mountain, Guangdong. A total of ten sites at different altitude gradients in Luofu Mountain were selected and soil genetic horizon samples were collected. Soil physic-chemical properties, such as bulk density, soil particle-size composition, pH, SOC, TN, TP, total iron oxides (Fet), free iron oxides (Fed), amorphous iron oxides(Feo), CEC, etc, were determined to analyze the correlation of SOC, TN, TP, C:N ratio, C:P ratio, N:P ratio with altitude gradients, physic-chemical properties. Our findings suggest that with the increase of soil depth, SOC, TN, TP, C:N ratio, C:P, and N:P in Luofu Mountain decreased, While with the increase of altitude, SOC, TN, TP, C:P, N:P increased, C:N ratio increased, and SOC, TN, TP highly significantly or significantly correlated with altitude. Pearson correlation analysis showed that SOC, TN, TP had highly significant positive correlations with silt, Feo, Feo:Fed, CEC. SOC and TN were highly significantly or significantly negatively correlated with clay, bulk density, Fet, Fed. TP had highly significant negative correlation with bulk density; C:N ratio, C:P ratio and N:P ratio showed highly significant positive correlation with CEC, while were highly significantly negatively correlated with bulk density, Fet, Fed. Redundancy analysis (RDA) showed that bulk density, clay, CEC, Fet, Feo and sand had highly significant effect on the stoichiometric characteristics of SOC, TN, TP, while altitude, pH, Fed, Fed:Fet ratio and Feo:Fed ratio had no significant effect. It was found that bulk density, clay, CEC, Fet and Feo are main soil physic-chemical factors that regulate the stoichiometric characteristics of SOC, TN, TP at different altitudes in the study area. [ABSTRACT FROM AUTHOR]

Hydrophobic organic contaminated polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs) and CHNS (carbon, hydrogen, nitrogen and sulphur species) are explosively associated with road dust particles. A few organic contaminants are toxic in nature and have an unpleasant effect on human health. The International Agency for Research on Cancer (IARC), the US Department of Health and Human Services (HHS) and the United States–Environmental Protection Agency has considered several PAHs and PCBs as carcinogens for human beings. In the proposed study, the anthropogenic contaminants present in road dust were assessed in six representative diversified sites i.e. industrial, commercial, office, residential, construction and traffic intersection in Delhi NCR, India. Roadside dust samples were gathered in premonsoon, monsoon and postmonsoon seasons and characterized for PAHs, PCBs and CHNS. The concentration of total PAHs (16 Nos) and PCBs (6 Nos) of the selected sites ranged from 0.27 µg/kg to 605.80 µg/kg and 0.01 µg/kg to 41.26 µg/kg, respectively. The Fourier transform infrared spectroscopy-attenuated total reflectance study suggested that the presence of O = C = O, Si–O, carbonyl, acidic or aliphatic esters group were associated with road dust particles. Hydrogen and sulphur concentrations were not detected in the selected road dust samples. Carbon and nitrogen concentrations varied from 2.24% to 16.82% and 0.69% to 14.5%, respectively, seasonally. In the premonsoon season, road dust was distinguishably contaminated as compared to monsoon and postmonsoon season, which might be due to movement of contaminated road dust from adjacent locations. It was perceived that Delhi NCR organic contamination in road dust was much below as compared to other countries. It may be concluded that due to the presence of significant amounts of carbon and nitrogen concentrations in the road dust, to a greater extent, road dust can be fertile and might be advantageous for green belt development to mitigate air pollution. The utilization of road dust will further bring down the burden of landfill sites and may lead towards sustainability. [ABSTRACT FROM AUTHOR]

Copyright of Pearl River is the property of Pearl River Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background Higher blood pressure variability (BPV) is associated with the development of major vascular diseases, independent of mean blood pressure. However, despite data indicating that serum inflammatory markers are linked to hypertension, the association between serum inflammatory markers and BPV has not been studied in humans. Methods This is a post hoc analysis of the Multi-Ethnic Study of Atherosclerosis (MESA) study. The study exposure was tertiles of serum level of interleukin-6 (IL-6), C-reactive protein (CRP), d-dimer, plasmin–antiplasmin complex (PAP), fibrinogen antigen, and calibrated Factor VIII (%) at the baseline study visit. The primary outcome was visit-to-visit BPV measured as the residual standard deviation (rSD) of at least 4 study visits (2000–2018). Two logistic regression models were fit to the top tertile of rSD during follow-up: in Model 1, we adjusted for age, sex, and hypertension, and in Model 2, for patient age categories, sex, race/ethnicity, education, hypertension, diabetes, smoking, drinking, body mass index, lipid-lowering medication, and mean systolic blood pressure. Results Our analysis included 5,483 patients, with a mean (SD) age of 61.4 (10.0) years, 52.9% female, and 40.7% White. In unadjusted analyses, all markers of inflammation were associated with higher BPV, but after adjustment, only IL-6 retained significance (P < 0.001). The odds ratio for the highest tertile of BPV and IL-6 was 1.49 (95% confidence interval [CI] 1.28–1.74, P < 0.001). Conclusions Baseline serum IL-6 was associated with increased subsequent BPV in a large multiracial cohort. Further investigation is needed to better understand the relationship between chronic inflammation and BPV. [ABSTRACT FROM AUTHOR]

Background: The increasing number of cancer cases requires developing newer approaches to treat this disease. One approach uses natural compounds with known anticancer effects, such as tocotrienols. Many cell-based and animal-model studies found that tocotrienols possess potent anticancer activities. However, the exact molecular regulatory mechanism through which tocotrienols exert anticancer actions remains unclear. Methods: This scoping review analysed data from original research articles reporting on the anticancer effects of tocotrienols on human cancer cell lines published in the last seven years (January 2015 and September 2021) using a systematic scoping review approach. From the initial 619 research papers [ProQuest (n= 61), PubMed (n= 84), Embase (n = 148), Ovid Medline (n =53), Scopus (n = 137), Web of Science (n =136)] identified using pre-defined keywords, only 37 articles met the inclusion and exclusion criteria for this review. Human cancers commonly studied in the 37 research articles include breast, lung, prostate and colorectal cancer cell lines. Results: The analysis showed that exposing human cancer cell lines to tocotrienols triggered common anticancer mechanisms such as activation of apoptosis and inhibition of proliferation, angiogenesis and cell migration through regulation of key regulatory genes and proteins involved in these pathways. Conclusions: The findings show that tocotrienols regulate a number of biomarkers that induce cell death and regulate cell cycle in various types of human cancer cells. Further targeted studies are required to map the definite pathways by which T3 exerts their action and to better understand the cellular actions and the regulatory pathways.

cGMP plays a role in sensory signaling and plasticity by regulating ion channels, phosphodiesterases, and kinases. Studies that primarily used genetic and biochemical tools suggest that cGMP is spatiotemporally regulated in multiple sensory modalities. FRET- and GFP-based cGMP sensors were developed to visualize cGMP in primary cell culture and Caenorhabditis elegans to corroborate these findings. While a FRET-based sensor has been used in an intact animal to visualize cGMP, the requirement of a multiple emission system limits its ability to be used on its own as well as with other fluorophores. Here, we demonstrate that a C. elegans codon-optimized version of the cpEGFP-based cGMP sensor FlincG3 can be used to visualize rapidly changing cGMP levels in living, behaving C. elegans We coexpressed FlincG3 with the blue-light-activated guanylyl cyclases BeCyclOp and bPGC in body wall muscles, and found that the rate of change in FlincG3 fluorescence correlated with the rate of cGMP production by each cyclase. Furthermore, we show that FlincG3 responds to cultivation temperature, NaCl concentration changes, and sodium dodecyl sulfate in the sensory neurons AFD, ASEL/R, and PHB, respectively. Intriguingly, FlincG3 fluorescence in ASEL and ASER decreased in response to a NaCl concentration upstep and downstep, respectively, which is opposite in sign to the coexpressed calcium sensor jRGECO1a and previously published calcium recordings. These results illustrate that FlincG3 can be used to report rapidly changing cGMP levels in an intact animal, and that the reporter can potentially reveal unexpected spatiotemporal landscapes of cGMP in response to stimuli.

We report the discovery of a third planet transiting the star TOI-1260, previously known to host two transiting sub-Neptune planets with orbital periods of 3.127 and 7.493 d, respectively. The nature of the third transiting planet with a 16.6-d orbit is supported by ground-based follow-up observations, including time-series photometry, high-angular resolution images, spectroscopy, and archival imagery. Precise photometric monitoring with CHEOPS allows to improve the constraints on the parameters of the system, improving our knowledge on their composition. The improved radii of TOI-1260b and TOI-1260c are |$2.36 \pm 0.06 \rm R_{\oplus }$|⁠ , |$2.82 \pm 0.08 \rm R_{\oplus }$|⁠ , respectively while the newly discovered third planet has a radius of |$3.09 \pm 0.09 \rm R_{\oplus }$|⁠. The radius uncertainties are in the range of 3 per cent, allowing a precise interpretation of the interior structure of the three planets. Our planet interior composition model suggests that all three planets in the TOI-1260 system contains some fraction of gas. The innermost planet TOI-1260b has most likely lost all of its primordial hydrogen-dominated envelope. Planets c and d were also likely to have experienced significant loss of atmospheric through escape, but to a lesser extent compared to planet b. [ABSTRACT FROM AUTHOR]

Cadaver-decomposition unleashes an ephemeral pulse of matter input that modifies microbial communities, as well as nutrient pools and fluxes. This leaves behind a measurable imprint on affected soils. However, the persistence of this imprint remains poorly understood. We define cadaver imprint persistence as the entire period between time of cadaver deposition and time when cadaver effects on microbial community structure and chemical indicators are no longer detectable. We present a brief overview of published results on the cadaver-induced changes in the bio-elements carbon, nitrogen and phosphorus, which regulate the structure and functions of the soil microbiome. Based on this, we identified conceptual and methodological gaps and biases and suggest potential research avenues to address them. This will help to better understand the relationships between cadaver-derived matter and microbial taxa and functions, as well as the role of cadaver-decomposition within and across ecosystems. The proposed future research on cadaver-derived imprint on soils has the potential to serve as a hub for connecting soil chemistry, microbial ecology, forensic sciences, and ecosystems science. [ABSTRACT FROM AUTHOR]

Fires are one of the most widespread factors of changes in the ecosystems of boreal forests. The paper presents the results of a study of the morphological and physicochemical properties and soil organic matter (SOM) of Albic Podzols under pine forests (Pinus sylvestris L.) of the middle taiga zone of Siberia (Krasnoyrsky kray) with various time passed after a surface fire (from 1 to 121 years ago). The influence of forest fires in the early years on the chemical properties of Albic Podzols includes a decrease in acidity, a decrease in the content of water-soluble compounds of carbon and nitrogen and an increase in the content of light polycyclic aromatic hydrocarbons (PAHs) in organic and upper mineral horizons. Podzols of pine forests that were affected by fires more than forty-five years ago are close to manure forest soils according to most physical and chemical properties. Significant correlations were found between the thickness (r = 0.75, p < 0.05), the moisture content (r = 0.90, p < 0.05) of organic horizons and the content of ∑PAHs in the organic horizon (r = −0.71, p < 0.05) with the time elapsed after the fire (i.e., from 1 to 121 years). The index of the age of pyrogenic activity (IPA) calculated as the ratio of ∑ PAHs content in the organic horizon to ∑ PAHs at the upper mineral horizon is significantly higher in forests affected by fires from 1 to 23 years than for plots with «older» fires (45–121 years). Thus, the article presents the conserved and most changing factors under the impact of fires in the boreal forests of Russia. [ABSTRACT FROM AUTHOR]

Porous carbons can be prepared from crystalline metal–organic frameworks (MOFs) by pyrolysis. However, MOF-derived porous carbons (denoted as MPCs) are mostly composed of microporosity, potentially causing diffusional limitation during guest transport. To overcome the potential diffusional limitation of MPCs due to pore size constraints, secondary meso- or macropores need to be introduced in the MPCs. Our strategy is to granulize MOF-808 nanoparticles via spray drying, followed by pyrolysis and HF etching, yielding MPC granules with a bimodal micro-mesoporous structure, in which the micropores originate from intrinsic pores of MOF-808 and the mesopores stem from interparticle spaces between assembled MOF-808 particles. [ABSTRACT FROM AUTHOR]

The scale and consequences of the transfer of biophilic elements from pasture ecosystems to sheep farms in the clayey semidesert of the northern Caspian region under grazing common in the region were estimated by the example of the settlement of Stepnovskoe, Pallasovskii district, Volgograd oblast. Data on the chemical composition of dominant plants and sheep feces, the long-term mean productivity of phytocenoses, information on the consumption of pasture forage by animals, etc. were used for the calculations. Soils of pastures, a reserve area, and a sheep farm (in sheep corrals and resting places) were investigated. At least 17 t C, 600 kg Ca, 260 kg N, 100 kg Mg, 50 kg K, 40 kg P, and 1 kg S were transferred to farms (0.1% of the area) from 1 ha of pasture (15% of the area) during 6 months of the grazing season. Long-term stocks of feces at farms (more than 1000 t at the examined farm) are practically excluded from the circulation in the landscape. Small areas of farm soils are enriched with C, N, P, and K. An increase in the stock of these elements in the upper 30-cm-thick layer of the soil of pastures comprises two orders of magnitude for water-soluble K, up to 12–16 times for exchangeable K, eight times for C, three times for N, and two times for available P in comparison with that in the soils of the reserve area. Grassland meadow-chestnut soils are characterized by a decrease in the content of C (1.3 times) and exchangeable forms of K (1.6 times) relative to soils of the reserve area. A decrease in the content of elements in solonetzes on pastures has not been found. The absence of statistically significant differences in the stocks of biophilic elements between the pasture soils and the soils of the protected reserve area is partly explained by an increase in soil density by 0.08 g/cm3 in the upper 50-cm layer on pastures. The modern farming method requires the control of the balance of biophilic elements in pasture soils. [ABSTRACT FROM AUTHOR]

Although the 2019 American Thoracic Society and Infectious Diseases Society of America guidelines for community-acquired pneumonia (CAP) recommend the use of antibiotics with Pseudomonas aeruginosa coverage for patients with prior sputum isolation of P. aeruginosa, further research is needed to confirm its clinical outcomes. This study aimed to assess the impact of the use of antibiotics with P. aeruginosa coverage on mortality in elderly CAP patients with sputum isolation of P. aeruginosa. We retrospectively included consecutive elderly patients who were hospitalized for CAP and P. aeruginosa -positive sputum culture. The association between the use of antibiotics with P. aeruginosa coverage and 28-day mortality was assessed based on propensity score to reduce selection bias. A total of 216 patients were included, and 68 (31%) of them were treated with antibiotics with P. aeruginosa coverage. The number of patients treated with antibiotics with P. aeruginosa coverage was significantly higher among nonsurvivors than among survivors. After adjustment using propensity score, the association between the use of antibiotics with P. aeruginosa coverage and the 28-day mortality was found to be statistically nonsignificant (odds ratio 2.182, 95% confidence interval 0.732–6.508, p = 0.162). The use of antibiotics with P. aeruginosa coverage in elderly CAP patients with sputum isolation of P. aeruginosa did not improve their prognosis. A randomized control study is required to identify cases that should be treated with antibiotics covering P. aeruginosa. [ABSTRACT FROM AUTHOR]

BK virus associated hemorrhagic cystitis(BKV-AHC) is a serious complication observed after allogeneic stem cell transplantation and the current therapeutic options are scarce with substantial renal side effects. Although the guidelines recommend intravenous cidofovir application with caution to nephrotoxicity, there are few studies which investigated intravesical administration and reported similar therapeutic results with less renal side effects. Methods: We administered low dose, daily and consecutive (75 mg/day, for 5 days) intravesical cidofovir to 25 patients with BKV-AHC that developed after (ASCT). Results: The response rate in our cohort was 92% and relapse was not encountered in 84% of the patient population during one year of follow-up. The median BK urine viral load significantly decreased from 260,000,000 IU/mL to 53,000,000 IU/mL after a week of treatment (p = 0.0001). Rise in serum creatinine was observed in 5 patients during treatment and post-treatment nephrotoxicity was seen in only 1 patient. Conclusions: Daily low dose intravesical cidofovir might be an effective treatment option for BKV-AHC after ASCT with favorable less systemic side effects. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Computer Sciences Institute is the property of Lublin University of Technology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Noni (Morinda citrifolia) fruit is a well-known plant used as a traditional medicine for preventing some diseases because of its abundance in chemical compounds. This research aimed to determine the phytochemical concentration, chemical composition, and antifungal activity of M. citrifolia fruit extract. M. citrifolia fruit was extracted with methanol and then distilled water for the partition extract. Subsequently, the extract was fractionated using various nonpolar to polar solutions, such as; chloroform, ethyl acetate, water, 2-propanol, and methanol fractions. Each fraction was evaporated until the dry extract was released. Additionally, the photochemical concentration of the M. citrifolia fruit extract was quantitatively determined using a UV-visible spectrophotometer. The chemical composition of the M. citrifolia fruit extract of each fraction was identified using gas chromatography-mass spectrometry (GCMS). Then, the antifungal activity of M.citrifolia fruit extract against C. albicans and C. krusei was determined using the disc diffusion method. The results showed that the phytochemical concentration of the M. citrifolia fruit extract was 1970.25 ppm flavonoids, 35.61 ppm tannins, and 148.62 ppm steroids. 2-Fluorobenzoic acid, eucalyptol, 2-chloroaniline-5-sulfonic acid, hexa-decamethyl octasiloxane, and tetra-propyl stannane were found to be the major components of M. citrifolia fruit extract. According to the research, M. citrifolia fruit extract showed antifungal activity against C. albicans and C. krusei in all tested fractions. The maximum inhibition zone of C. albicans was 14.0 ± 1.00 mm in the 2-propanol fraction, while that of C. krusei was 11.7 ± 0.58 mm in the methanol fraction. [ABSTRACT FROM AUTHOR]

Water level and submergence time are important factors influencing plant growth and plant C:N:P characteristics in freshwater wetlands. Here, we performed a controlled experiment using water levels and submergence times with the aim of investigating the changes in plant growth and stoichiometric characteristics, as well as the strength of N, P, and N:P homeostasis in Carex brevicuspis, China. Results showed that biomass, density, height, and total carbon (TC) decreased significantly with increasing water level; however, total nitrogen (TN) and total phosphorus (TP) increased significantly. The highest TN and TP were at 40 cm water level, while the highest C:N, C:P, and N:P ratios were at 0 cm water level. Furthermore, significant stoichiometric homeostasis of C. brevicuspis was found for N (HN) and P (HP) except for N:P (HN:P). HN and HP decreased with increasing submergence time, and HN was consistently greater than HP, indicating that C. brevicuspis had a weak ability to maintain its internal P balance under long-term submergence. Therefore, the impact of water level and submergence time on plant growth and stoichiometric characteristics in this study are applicable to the conservation and management of the wetlands dominated with C. brevicuspis. [ABSTRACT FROM AUTHOR]

To assess the public health impact and cost effectiveness of gender-neutral vaccination (GNV) versus female-only vaccination (FOV) with human papillomavirus (HPV) vaccination in Japan. We modeled the public health impact and cost effectiveness of GNV versus FOV to prevent HPV-associated diseases in Japan over the next 100 years. We used one-way sensitivity analyses to examine the impact of varying key model input parameters and conducted scenario analyses to explore the effects of varying the vaccination coverage rate (VCR) of each cohort. In the base-case analysis, GNV averted additional cancer cases (17,228 female/6,033 male) and deaths (1,892 female/1,849 male) compared to FOV. When all HPV-associated diseases were considered, GNV had an incremental cost-effectiveness ratio of ¥4,732,320 (US$35,987)/quality-adjusted life year gained compared to FOV. The model was most sensitive to the discount rate and the disutility associated with HPV-related diseases. GNV had greater relative public health benefits when the female VCR was lower and was cost effective at a female VCR of 30%. Immediate implementation of GNV would reduce the disease burden and mortality associated with HPV in Japan, and would be cost effective compared to FOV if the female VCR remains low (30%). Human papillomavirus (HPV) is a common sexually transmitted infection and, in Japan, the prevalence of HPV infection and the incidence of its associated diseases are high among both men and women. In the present manuscript we modeled the public health impact and cost effectiveness of gender-neutral vaccination versus female-only vaccination to prevent HPV-associated diseases in Japan over the next 100 years and found that immediate implementation of a gender-neutral vaccination strategy would reduce the burden and mortality associated with HPV in Japan. [ABSTRACT FROM AUTHOR]

French guidelines for the management of non-muscle-invasive bladder cancer recommend that blue-light cystoscopy should be used in patients where the risk of missing residual tumor is highest. Despite evidence for its cost-effectiveness, budgetary concerns have limited uptake in France. The aim of this analysis was to model the cost-consequences of adopting the recommendations in a French urology unit. A budget impact model was developed in Excel, using a decision tree approach derived from guidelines issued by L'Academie franҫaise d'urologie. Risk profiles were derived from an analysis of studies using white-light cystoscopy; estimates for the impact of blue-light cystoscopy were derived from a published Cochrane Review. Costs were based on published tariff prices from L'Agence Technique de L'Information sur L'Hospitalisation. The model allowed results to be tailored to activity levels and projected blue-light usage in the chosen urology unit. Two scenarios were evaluated, based on a 3-year time horizon. Full implementation of all recommendations within a large public hospital was estimated to yield incremental costs of €269 per procedure (∼10% increase overall); a more targeted approach within a smaller private hospital yielded incremental costs of €133 per procedure (5% increase overall). The basis of the model is a change in the time to first recurrence. There are no data available for subsequent recurrences or progression, both of which could have an influence on expenditure. Secondly, recurrence rates for blue-light cystoscopy were not specifically available for each patient group identified in the guidelines: extrapolation of data may have resulted in bias. Finally, the data were derived from clinical trials, which may not be generalisable to real-world clinical practice. The model has shown that the additional expenditure required to implement blue-light cystoscopy is modest and not disproportionate to the overall cost of care. [ABSTRACT FROM AUTHOR]

The study objectives were to 1) characterize the cost drivers of patients with Helicobacter pylori (HP) and 2) estimate HP-related cost savings following lab-confirmed HP eradication with US guideline-recommended treatment compared to failed eradication. We identified adults newly diagnosed with HP between 1/1/2016–12/31/2019 in the Veradigm Electronic Health Record Database linked to claims data (earliest HP diagnosis = index date). For the overall costs analysis, we required patients to have data available for ≥12 months before and after the index date. Then, we used multivariable modeling to assess the marginal effects of comorbidities on all cause-healthcare costs in the 12 months following HP diagnosis. For the eradication savings analysis, we identified patients with ≥1 HP eradication regimen, a subsequent HP lab test result, and ≥1 year of data after the test result. Then we used multivariable modeling to estimate HP-related cost while adjusting for eradication status, demographics, post-testing HP-related clinical variables, and the interactions between eradication status and each HP-related clinical variable. The overall cost analysis included 60,593 patients with HP (mean age 54.2 years, 65.5% female). Mean (SD) 12-month unadjusted all-cause costs were $23,693 ($78,089). Rare comorbidities demonstrated the highest marginal effect. The marginal effects of gastric cancer and PUD were $15,705 and $7,323, respectively. In the eradication savings analysis, 1,835 (80.0%) of the 2295 patients had lab test-confirmed HP eradication. Compared to failed eradication, there were significant one-year cost savings among patients with successful HP eradication and select conditions: $1,770 for PUD, $518 for atrophic gastritis, $494 for functional dyspepsia, and $352 for gastritis. The healthcare costs of patients with HP are partially confounded by their burden of high-cost comorbidities. In the subset of patients with available results, confirmed vs. failed eradication of HP was associated with short-term cost offsets among those with specific to HP-related sequelae. Helicobacter pylori (HP) is a common infection. We aimed to better understand healthcare costs for people infected with HP. Specifically, we were interested in 1) investigating whether complications from HP were causing high costs. 2) whether successful eradication of HP would lead to lower healthcare costs. We captured data on adults diagnosed with HP between 2016 and 2019. The data used in this study came from medical records and insurance bills. In the first part of the study, we found that patients with HP often have other health issues, and these other health issues were driving high healthcare costs. The majority of cost savings associated with HP eradication accrue from the prevention of potential complications of long-term infection, such as peptic ulcer disease and, rarely, gastric cancer. [ABSTRACT FROM AUTHOR]

Hepatorenal syndrome (HRS) is characterized by severely reduced renal perfusion that precipitates rapid morbidity and mortality. Terlipressin is the only US Food and Drug Administration-approved treatment to improve kidney function for adults with HRS with a rapid reduction in kidney function. Prior to the approval of terlipressin, unapproved vasoconstrictive agents used in HRS treatment were octreotide/midodrine and norepinephrine with albumin. A cohort decision-tree model representing a US hospital perspective assessed the clinical outcomes and direct medical costs (based primarily on hospital charges) of treating HRS with terlipressin + albumin (ALB) versus midodrine/octreotide (MID/OCT)+ALB, or norepinephrine (NorEp)+ALB. Treatment efficacy was defined by clinical response (complete/HRS reversal, partial, or no response) based on change of serum creatinine derived from published clinical trial reports. The proportions of patients with complete response were: terlipressin + ALB (36.2%), NorEp + ALB (19.1%), and MID/OCT + ALB (3.1%). Model outcomes included utilization of HRS-related healthcare resources (hospital and intensive care, outpatient and emergency department, dialysis, and transplantations), adverse events, and HRS-related mortality. Outcomes were assessed for the initial hospitalization in the base case and at 30, 60, and 90 days post-discharge. Total costs incurred over the initial hospitalization with terlipressin + ALB were lower vs NorEp + ALB, primarily due to higher ICU costs with NorEp + ALB ($7,433 vs $61,897). TER + ALB was associated with higher total costs vs MID/OCT + ALB due to higher pharmacy costs with terlipressin + ALB. The cost per complete response achieved of terlipressin + ALB ($451,605) was half that of NorEp + ALB ($930,571) and one-tenth that of MID/OCT + ALB ($4,942,123). HRS patients treated with terlipressin experienced better clinical outcomes and a lower cost per treatment response vs other unapproved treatments. ICU days and pharmacy costs were key cost drivers distinguishing the treatment groups. These outcomes suggest that terlipressin is cost-effective on the basis of total cost per response achieved. Hepatorenal syndrome (HRS) is a rare and sudden life-threatening complication of the liver. Patients with HRS should receive immediate treatment with a drug that narrows blood vessels known as a vasoconstrictor. Terlipressin is the most common vasoconstrictor used for patients with HRS. Other common vasoconstrictors are midodrine with octreotide and norepinephrine. This study aimed to compare the cost of terlipressin with those of midodrine with octreotide and norepinephrine while also considering how well each of them worked to reverse HRS. This was done using an economic model. This economic model assessed the costs of the vasoconstrictor drugs and the costs of treating HRS, including costs attributable to drug acquisition, adverse events, organ transplantation, dialysis, and institutional encounters (i.e. hospitalization, ICU, emergency department, and outpatient visits). The magnitude of these costs depends on how well each drug reversed HRS. Based on inputs derived from their respective clinical trials, 36% of patients who were given terlipressin had a complete response (HRS was reversed), 19% of patients who were given norepinephrine had a complete response, and 3% of patients who were given midodrine with octreotide had a complete response. The total cost per patient was approximately $163,481 for terlipressin, $177,298 for norepinephrine, and $155,030 for midodrine with octreotide. When the costs were evaluated against how well the drugs worked to reverse HRS, the lowest cost per HRS reversal was $451,605 when treated with terlipressin. The cost per reversal for norepinephrine was $930,571 and for midodrine with octreotide was $4,942,123. These results show that terlipressin works well and is more cost-effective for US hospitals compared with the other unapproved treatment options for HRS with rapid reduction in kidney function. [ABSTRACT FROM AUTHOR]

The United States Preventive Services Taskforce (USPSTF) recently recommended lowering the age for average-risk colorectal cancer (CRC) screening from 50 to 45 years. While initiating screening at age 45 versus 50 provides a greater opportunity for CRC early detection and prevention, the full profile of benefits, risks, and cost-effectiveness of expanding the screen-eligible population requires further evaluation. The costs and clinical outcomes for screening at age 45 for triennial multi-target stool DNA [mt-sDNA], and other non-invasive stool-based modalities (annual fecal immunochemical test [FIT] and annual fecal-occult blood test [FOBT]), were estimated using the validated CRC-AIM microsimulation model over a lifetime horizon. Test sensitivity and specificity inputs were based on 2021 USPSTF modeling analyses; adherence rates were based on published real-world data and the costs of the screening test, follow-up colonoscopies, complications, and CRC care were included. Outcomes are reported from the perspective of a United States payer as clinical, life-years gained (LYG), and incremental cost-effectiveness ratio (ICER); stool-based and follow-up colonoscopy adherence ranges were explored in one-way, probabilistic and threshold analyses. When compared to initiation of CRC screening at age 45 versus 50, all modalities reduced both the incidence of and mortality from CRC and increased LYG. Initiating CRC screening at age 45 was cost-effective with an ICER of $59,816 and $35,857 per quality-adjusted life year (QALY) for mt-sDNA versus FIT and FOBT, respectively. In the threshold analyses, at equivalent rates to stool-based screening, mt-sDNA was always cost-effective at a willingness-to-pay threshold of $100,000 per QALY versus FIT and FOBT. Initiating average-risk CRC screening at age 45 instead of age 50 increases the estimated clinical benefit by reducing disease burden while remaining cost-effective. Among stool-based screening modalities, mt-sDNA provides the most clinical benefit in a Commercial and Medicare population. Screening for colorectal cancer at an earlier age can provide additional benefits in terms of reducing disease complications and death. This study looked at the occurrence of disease complications and costs related to different types of colorectal cancer screening in 45 vs. 50 year old people. A model that has previously been used to project lifetime costs and disease complications in people receiving colorectal cancer screening was used in this study. We found that beginning screening at age 45 as compared to at age 50 reduced disease complications and death. In people who started screening at age 45, one particular screening type (multitarget stool DNA) was found to provide better economic value to a greater degree relative to other strategies. These findings were consistent even when many inputs into the model were changed over reasonable ranges. Therefore, our study helps show that starting screening in people at age 45 with average risk for developing colorectal cancer is beneficial by reducing disease complications and deaths, and that multitarget stool DNA is the strategy that provides the most benefits while being economically justifiable. [ABSTRACT FROM AUTHOR]

We evaluated the pharmacoeconomic value of polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) in previously untreated diffuse large B-cell lymphoma (DLBCL) versus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). A 3-state partitioned survival model was used to estimate life years (LYs), quality-adjusted LYs (QALYs), and cost impacts of Pola-R-CHP versus R-CHOP. Analyses utilized mixture-cure survival modelling, assessed a lifetime horizon, discounted all outcomes at 3% per year, and examined both payer and societal perspectives. Progression-free survival, overall survival (OS), drug utilization, treatment duration, adverse reactions, and subsequent treatment inputs were based on data from the POLARIX study (NCT03274492). Costs included drug acquisition/administration, adverse reaction management, routine care, subsequent treatments, end-of-life care, and work productivity. Incremental cost-effectiveness ratios of Pola-R-CHP versus R-CHOP were $70,719/QALY gained and $88,855/QALY gained from societal and payer perspectives, respectively. The $32,824 higher total cost of Pola-R-CHP versus R-CHOP was largely due to higher drug costs ($122,525 vs $27,694), with cost offsets including subsequent treatment (–$52,765), routine care (–$1,781), end-of-life care (–$383), and work productivity (–$8,418). Pola-R-CHP resulted in an increase of 0.47 LYs and 0.46 QALYs versus R-CHOP. Pola-R-CHP was cost-effective in 60.9% and 58.0% of simulations at a willingness-to-pay threshold of $150,000/QALY gained from societal and payer perspectives, respectively. There was uncertainty around the OS extrapolation in the model, and costs were derived from different sources. Recommended prophylactic medications were not included; prophylactic use of granulocyte colony-stimulating factor for all patients was assumed to be equal across treatment arms in POLARIX. Work productivity loss was estimated from a general population and was not specific to patients with DLBCL. Pola-R-CHP was projected to be cost-effective versus R-CHOP in previously untreated DLBCL, suggesting that Pola-R-CHP represents good value relative to R-CHOP in this setting. [ABSTRACT FROM AUTHOR]

Nivolumab plus ipilimumab (NIVO + IPI) and pembrolizumab plus axitinib (PEM + AXI) have demonstrated significant clinical benefits as first-line (1 L) treatments for intermediate/poor-risk advanced renal cell carcinoma (aRCC) patients. This study aimed to assess the cost-effectiveness of NIVO + IPI versus PEM + AXI from a Brazilian private healthcare system perspective, utilizing a novel approach to estimate comparative efficacy between the treatments. A three-state partitioned survival model (progression-free, progressed, and death) was developed to estimate costs, life-years (LYs), quality-adjusted LYs (QALYs), and the incremental cost-utility ratio (ICUR) over a 40-year time horizon. In the absence of head-to-head comparisons between NIVO + IPI and PEM + AXI, clinical data for NIVO + IPI was obtained from CheckMate 214 (NCT02231749) and for PEM + AXI from KEYNOTE-426 (NCT02853331). A matching-adjusted indirect comparison was conducted to account for the imbalance of treatment effect modifiers between the trials. Patient characteristics, resource use, health state utilities, and costs were based on Brazilian-specific sources. Costs and health outcomes were both discounted by 5% annually in line with Brazilian guidelines. The robustness of the results was evaluated through extensive sensitivity analysis and scenario analyses. When comparing the matched versus unmatched OS, PFS, and TTD curves there was no noteworthy difference. NIVO + IPI was associated with cost savings (R$ 350,232), higher LYs (5.54 vs. 4.61), and QALYs (4.74 vs. 3.76) versus PEM + AXI, resulting in NIVO + IPI dominating PEM + AXI. Key model drivers were the treatment duration for PEM, NIVO, and AXI. NIVO + IPI remained dominant in all scenario analyses, which indicated that model results were robust to alternative modelling inputs or assumptions. This analysis shows that NIVO + IPI is estimated to be a life-extending and potentially cost-saving 1 L treatment option when compared with PEM + AXI for intermediate/poor-risk a RCC patients in the Brazilian private healthcare system. Nivolumab plus ipilimumab (NIVO+IPI) and pembrolizumab plus axitinib (PEM+AXI) are currently the two most prescribed therapies in the Brazilian private healthcare market for the first-line (1L) treatment of intermediate/poor-risk advanced renal cell carcinoma (RCC) patients. Given that financial resources are limited, economic evaluations are needed to enable Brazilian payers to make informed decisions. In order to provide robust evidence on the relative costs and benefits of 1L RCC treatments in the Brazilian private healthcare system, the cost-effectiveness of NIVO+IPI versus PEM+AXI was evaluated using a three-state model. This model simulates the patient's journey, where a patient can remain free of disease progression, experience disease progression, or die. To reflect the Brazilian situation, patient characteristics, healthcare resource use and costs, and quality-of life data in the model were based on Brazilian sources. NIVO+IPI and PEM+AXI have not been compared "head-to-head" in a clinical trial, therefore treatment efficacy was estimated using a matching-adjusted indirect comparison, a method that uses patient-level data from one trial (Checkmate 214) to match summary patient characteristics from the comparator trial (KEYNOTE-426), thus enabling a robust comparison. Model results showed that NIVO+IPI was associated with cost savings (R$ 350,232), higher life-years (5.54 vs 4.61), and quality-adjusted life-years (4.74 vs 3.76) versus PEM+AXI, resulting in NIVO+IPI being less costly and providing more clinical benefits than PEM+AXI. By showing that NIVO+IPI is a life-extending and cost-saving 1L treatment option when compared with PEM+AXI for intermediate/poor-risk aRCC patients, this study can help Brazilian payers make value-based choices on their resource allocation. [ABSTRACT FROM AUTHOR]

The objective of this study was to estimate and compare the cost-effectiveness of switching from a bivalent to a nonavalent human papillomavirus (HPV) vaccination program in Norway, incorporating all nonavalent vaccine-preventable HPV-related diseases and in the context of the latest cervical cancer screening program. A well-established dynamic transmission model of the natural history of HPV infection and disease was adapted to the Norwegian population. We determined the number of cases of HPV-related diseases and subsequent number of deaths, and the economic burden of HPV-related disease under the current standard of care conditions of bivalent and nonavalent vaccinations of girls and boys aged 12 years. Compared to bivalent vaccination, nonavalent vaccination averted an additional 4,357 cases of HPV-related cancers, 421,925 cases of genital warts, and 543 cases of recurrent respiratory papillomatosis (RRP) over a 100-year time horizon. Nonavalent vaccination also averted an additional 1,044 deaths over the 100-year time horizon when compared with bivalent vaccination. Total costs were higher for the nonavalent strategy (10.5 billion NOK [€1.03 billion] vs. 9.3–9.4 billion NOK [€915–925 million] for bivalent vaccination). A switch to nonavalent vaccination had a higher vaccination cost (4.4 billion NOK [€433 million] vs. 2.7 billion NOK [€266 million] for bivalent vaccination) but resulted in a savings of 627–694 million NOK [€62–68 million] in treatment costs. A switch to nonavalent vaccination demonstrated an incremental cost-effectiveness ratio of 102,500 NOK (€10,086) per QALY versus bivalent vaccination. Using a model that incorporated the full range of HPV-related diseases, and the latest cervical cancer screening practices, we found that switching from bivalent to nonavalent vaccination would be considered cost-effective in Norway. Human papillomavirus (HPV) is a sexually transmitted infection that is common in Norway. Vaccination against HPV has substantially reduced the burden of HPV-related diseases globally. The HPV vaccine is available in bivalent, quadrivalent, and nonavalent forms. The bivalent vaccine is currently used in the Norwegian national immunization program, but the nonavalent vaccine is also licensed in Norway. In order to gain a more complete understanding of the benefits of nonavalent vaccination, it is necessary to evaluate the cost-effectiveness of switching from the bivalent vaccine to the nonavalent vaccine in light of the full array of vaccine-preventable diseases, including both cervical and noncervical cancers, genital warts, and recurrent respiratory papillomatosis (RRP). Our results show that, when the full range of HPV-related diseases is considered, nonavalent vaccination would be cost-effective relative to bivalent vaccination in Norway. Compared to bivalent vaccination, nonavalent vaccination averted an additional 4,357 cases of HPV-related cancers, 421,925 cases of genital warts, and 543 cases of RRP over a 100-year time horizon. Nonavalent vaccination also averted an additional 1,044 deaths over the 100-year time horizon when compared with bivalent vaccination. While total costs were higher for the nonavalent strategy (10.5 billion NOK [€1.03 billion] vs. 9.3-9.4 billion NOK [€915–925 million] for bivalent vaccination), switching to the nonavalent strategy resulted in a savings of 627–694 million NOK [€62–68 million] in treatment costs compared to the bivalent strategy. [ABSTRACT FROM AUTHOR]

To assess the cost-effectiveness of transarterial radioembolization (TARE) versus conventional transarterial chemoembolization (cTACE) and drug-eluting beads chemoembolization (DEE-TACE) for patients with unresectable early- to intermediate-stage hepatocellular carcinoma (HCC). A cohort-based Markov model with a five-year time horizon was developed to evaluate the cost-effectiveness of the three embolization treatments. Upon entering the model, patients with HCC received either TARE or one of the two other embolization treatments. Patients remained in a "watch and wait" state for tumor downstaging that allowed them to move to health states such as liver transplant, resection, systemic therapies, or cure. Clinical input parameters were retrieved from the published literature, and where values could not be sourced, assumptions were made and validated by clinical experts. Health benefits were quantified using quality-adjusted life years (QALYs). Cost input parameters were obtained from various sources, including the Medicare Cost Report, IBM® Micromedex RED BOOK, and published literature. At five years, TARE was found to be cost-saving (saving $15,779 per person compared to cTACE) and produced 0.33 more QALYs per person than cTACE. TARE cost $13,696 more but produced 0.33 more QALYs than DEE-TACE, with an incremental cost-effectiveness ratio of $41,474 per QALY gained at five years. After accounting for parameter uncertainty, the likelihood of TARE being cost-effective was at least 90% against all comparators at a cost-effectiveness threshold of $100,000 per QALY gained. TARE produces more QALYs than cTACE and DEE-TACE, with a high probability of being cost-effective against both comparators. The Barcelona Clinic Liver Cancer guideline recommends the use of transarterial radioembolization (TARE), conventional (cTACE), or drug-eluting bead transarterial chemoembolization (DEE-TACE) for treating hepatocellular carcinoma (HCC). This study evaluated the cost-effectiveness of TARE versus two alternative embolization treatments (cTACE and DEE-TACE) in treating patients with unresectable early- to intermediate-stage HCC. A cohort-based Markov model was developed to analyze the costs and benefits of these treatments from a US healthcare perspective within a 5-year time horizon. A 20-year time horizon was assessed as a scenario. In the model, patients were assigned to receive TARE, cTACE, or DEE-TACE and remained in the "watch and wait" stage for tumor downstaging. Data used in the model was taken from previous studies and in consultation with clinical experts. The benefits of the treatments were measured by considering the impact on the patient's quality of life. The costs associated with the treatments were obtained from various sources, including reports, publicly available databases, and published literature. The findings show that TARE is not only cost-saving compared to cTACE but also results in a higher number of quality-adjusted life years (QALYs) per person. While TARE was more expensive than DEE-TACE, it produced more QALYs, further indicating more favorable patient outcomes and overall treatment effectiveness. These findings could potentially impact resource allocation and decision-making for the treatment of HCC. [ABSTRACT FROM AUTHOR]

Apixaban and rivaroxaban are two direct-acting oral anticoagulants (DOACs) recommended for thromboprophylaxis in cancer patients treated with chemotherapy in an ambulatory setting. We aimed to assess the cost-utility of thromboprophylaxis with apixaban and rivaroxaban vs no thromboprophylaxis in ambulatory cancer patients starting chemotherapy with an intermediate-to-high risk of venous thromboembolism (VTE), Khorana score ≥ 2 points. A cost-effectiveness analysis was performed from the perspective of Spain's National Health System (NHS) using an analytical decision model in the short-term (180 days) and a Markov model in the long-term (5 years). Transition probabilities were obtained from randomized, double-blind, placebo-controlled clinical trials of apixaban and rivaroxaban in adult ambulatory patients with cancer at risk for VTE, treated with chemotherapy (AVERT and CASSINI trials). The costs (€2,021) were taken from Spanish sources. The utilities of the model were obtained through the EQ-5D questionnaire. Deterministic (base case) and probabilistic (second-order Monte Carlo simulation) analyses were conducted. In the probabilistic sensitivity analysis, apixaban generated a cost per patient of €1,082 ± 187, with a 95% confidence interval (CI) of €713–1,442, while no prophylaxis produced a cost per patient of €1,146 ± 218, with a 95% CI of €700–1,491, with a saving of €64 per patient and a gain of 0.008 QALYs. Likewise, rivaroxaban provided a cost per patient of €993 ± 133, with a 95% CI of €748–1,310, while no prophylaxis produced a cost per patient of €872 ± 152, with a 95% CI of €602–1,250, with an additional expense of €121 per patient and a gain of 0.008 QALYs. In thromboprophylaxis of cancer patients, the use of apixaban and rivaroxaban generated similar costs compared to non-prophylaxis, without the difference found being statistically significant, with a clinically insignificant QALY gain. [ABSTRACT FROM AUTHOR]

This study aimed to estimate the 10-year cost-consequence of weight loss on obesity-related outcomes in a sample of privately insured adults with obesity in Saudi Arabia (KSA). We analyzed data of adults with obesity (BMI ≥ 30 kg/m2) available in Nphies, the private health insurance platform of the Council of Health Insurance, KSA. A micro-costing analysis was used to obtain domestic cost estimates for obesity-related outcomes. Cox proportional hazard models were used to estimate the benefit of weight loss by preventing incident cases of 10 obesity-related outcomes. In the study cohort (n = 314,079), the 30–34.9 BMI category contributed two-thirds of the cohort, and no gender differences were found in the age distribution of BMI categories. The elderly population had a higher prevalence of obesity-related outcomes, such as hypertension, osteoarthritis, and type 2 diabetes mellitus (T2DM). The baseline cost (2023) for treating these outcomes was USD 1.245 billion, which could double in 10 years. A 15% weight loss could save USD 1.295 billion over 10 years, with most savings due to T2DM (USD 430 million), given its higher prevalence (27.5%). The model was most sensitive to cost variability in T2DM, dyslipidemia, and hypertension. The results should be interpreted within the bounds of the study cohort, and Nphies is in its early stages of implementation. The cost estimates may differ if repeated among adults with obesity only, potentially leading to increased cost savings with weight loss. Moderate weight loss of 5–15% over 10 years is associated with substantial cost savings in Saudi Arabia. For a 15% weight loss, 18.8% of incidence cases of obesity-related outcomes may be prevented, and slowed increases in T2DM, dyslipidemia, and hypertension may lead to considerable cost savings. The findings would help policymakers to implement weight loss programs in KSA. [ABSTRACT FROM AUTHOR]

Pimavanserin (PIM) is the only FDA approved atypical antipsychotic (AAP) for the treatment of Parkinson's Disease Psychosis (PDP) while other off-label AAPs like quetiapine (QUE) are also used. Real-world comparative effects of PIM and QUE on health resource utilization (HCRU) may provide insights about their relative benefits. To examine annual HCRU among newly initiated PIM or QUE monotherapy among patients with PDP. Retrospective analysis of 100% Medicare (Parts A, B, and D) claims of patients with PDP during 1 January 2013 to 31 December 2019 was conducted. Treatment-naive patients with first prescription for PIM or QUE from 1 January 2014 to 31 December 2018 were selected if they had ≥12-months continuous monotherapy and had no prior AAP use for ≥12-month pre-index. Post-index 12-month HCRU was compared between 1:1 propensity score matched (PSM) PIM or QUE cohorts. HCRU outcomes included: rates of all-cause and psychiatric-related inpatient hospitalizations by stay-type [i.e., long-term stays (LT-stays), short-term stays (ST-stays), skilled nursing facility stays (SNF-stays)], outpatient hospitalizations, emergency room (ER) visits, and office visits. Relative risk and 95% confidence intervals are reported [RR (95% CI)]. A total of 842 and 7,116 were treated with PIM and QUE, respectively. Mean age and gender distribution were similar among both groups. After PSM, those on PIM (n=842) had significantly lower RR for all-cause: inpatient hospitalizations [RR=0.78 (0.70–0.87)], ST-stays [RR=0.75 (0.66–0.84)], SNF-stays [RR=0.64 (0.54–0.76)], and ER visits [RR=0.91 (0.84–0.97)] vs. QUE (n=842). PIM patients had slightly higher RR for all-cause office visits [RR=1.03 (1.01–1.05)] vs. QUE. Psychiatric-related inpatient hospitalizations were also lower for PIM vs. QUE: [RR=0.63 (0.48–0.82)] ST-stays [RR=0.61 (0.43–0.86)], SNF-stay [RR=0.69 (0.47–1.02)], and ER visits [RR=0.53 (0.37–0.76)]. In this analysis of PDP patients, PIM monotherapy resulted in nearly 22% and 37% lower all-cause hospitalizations and psychiatric-related inpatient hospitalizations compared to QUE. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a severe condition with poor prognosis that places a significant burden on patients, caregivers, and healthcare systems. Selective internal radiation therapy (SIRT) is a treatment available to patients with HCC which addresses some of the limitations of alternative treatment options. A cost-effectiveness analysis was undertaken into the use of SIRT using Y-90 resin microspheres for the treatment of unresectable intermediate- and late-stage HCC in Brazil. A partitioned-survival model was developed, including a tunnel state for patients downstaged to receive treatments with curative intent. Sorafenib was the selected comparator, a common systemic treatment in Brazil and for which comparative evidence exists. Clinical data were extracted from published sources of pivotal trials, and effectiveness was measured in quality-adjusted life-years (QALYs) and life-years (LYs). The analysis was conducted from the Brazilian private payer perspective and a lifetime horizon was implemented. Comprehensive sensitivity analyses were conducted. LYs and QALYs were higher for SIRT with Y-90 resin microspheres versus sorafenib (0.27 and 0.20 incremental LYs and QALYs, respectively) and costs were slightly higher for SIRT (R$15,864). The base case incremental cost-effectiveness ratio (ICER) was R$77,602 per QALY. The ICER was mostly influenced by parameters defining the sorafenib overall survival curve and SIRT had a 73% probability of being cost-effective at a willingness-to-pay threshold of R$135,761 per QALY (3-times the per-capita gross domestic product in Brazil). Overall, sensitivity analyses confirmed the robustness of the results indicating that SIRT with Y-90 resin microspheres is cost-effective compared with sorafenib. A rapidly evolving treatment landscape in Brazil and worldwide, and the lack of local data for some variables were the main limitations. SIRT with Y-90 resin microspheres is a cost-effective option compared with sorafenib in Brazil. [ABSTRACT FROM AUTHOR]

Gastro-esophageal reflux disease (GERD) is a common, chronic gastrointestinal condition characterized by heartburn, chest pain, regurgitation, and bloating. The current standard of care includes chronic treatment with proton pump inhibitors (PPIs) or, in selected patients, laparoscopic anti-reflux surgery. RefluxStop is a novel implantable device indicated for GERD patients eligible for laparoscopic surgical treatment. The aim of this analysis was to assess the cost-effectiveness of RefluxStop against available treatment options for GERD. A Markov model was developed to assess the cost-effectiveness of RefluxStop compared with PPI-based medical management (MM) and two surgical management options, LNF and magnetic sphincter augmentation (MSA, LINX system), in people with GERD. Clinical outcomes and costs were estimated over a lifetime horizon from the UK National Health Service perspective and an annual discount rate of 3.5% was applied. RefluxStop showed favorable surgical outcomes compared with both LNF and MSA. The base case incremental cost-effectiveness ratios compared with MM, LNF, and MSA were £4,156, £6,517, and £249 per QALY gained, respectively. At the UK cost-effectiveness threshold of £20,000 per QALY gained, the probability that RefluxStop was cost-effective against MM, LNF, and MSA was 100%, 93%, and 100%, respectively. The model presented the results of a comparison, with evidence for RefluxStop derived from its single-arm CE mark trial and that for comparators from the literature. The varied clinical care pathway of individual GERD patients was necessarily simplified for modeling purposes, and necessary assumptions were made; however, the model results proved robust to sensitivity analyses. Introduction of RefluxStop was estimated to extend life expectancy and improve quality-of-life of GERD patients when compared with MM, LNF, and MSA. The results of the cost-effectiveness analysis demonstrated that RefluxStop is highly likely to be a cost-effective treatment option within NHS England. [ABSTRACT FROM AUTHOR]

Assessing the value of single or short-term therapies (SSTs) within traditional cost-effectiveness analyses (CEAs) has been a topic of discussion as the number of SSTs increases, particularly regarding the effect of discounting on valuation. To quantify the impact of discounting in economic evaluations, a CEA of a hypothetical SST and equivalent chronic therapy was conducted using standard methods. A lifetime Markov model was developed for a hypothetical chronic, progressive disease that could be treated with an SST, chronic therapy, or no novel treatment, termed standard of care (SoC). Incremental cost-effectiveness ratios (ICERs) with quality-adjusted life years (QALYs) comparing SST vs. SoC and an equivalent chronic therapy vs. SoC were assessed from a payer perspective. Both treatments had equal benefits and undiscounted lifetime costs; 3% discounting was applied to costs/benefits in the base case, and the impact of discounting was assessed. In the base case example, both the SST and equivalent chronic therapy vs. SoC had ICERs of $86,000/QALY without discounting. With 3% discounting, the ICER for the SST increased by 116% ($186,000/QALY) while the ICER for the chronic therapy increased by 10% ($95,000/QALY) despite equal clinical benefit. In scenario analyses, the ICER of the SST was consistently higher than the equivalent chronic therapy across a range of assumptions/inputs. Varying the cost/benefit discount rates had a greater impact on the SST. Differences in the ICERs between the therapies increased with increasing life expectancy/time horizon. The simple model structure may not be reflective of acute or more complex diseases. Also, the scenario of perfect equivalency in efficacy and lifetime costs is hypothetical. This quantitative assessment showed the extent to which SST CEAs are highly sensitive to discounting, resulting in worse value assessments for SSTs than equivalent chronic therapies. [ABSTRACT FROM AUTHOR]

This study estimated the "process utilities" of treatment options for patients with relapsed/refractory multiple myeloma (RRMM) in Japan using the time trade-off (TTO) method. Chimeric antigen receptor (CAR) T cell immunotherapy is available for patients with RRMM who are triple-class exposed (TCE) after treatment with immunomodulatory agents, proteasome inhibitors, and anti-CD38 monoclonal antibodies. However, the impact of available treatment options on health state utilities has not been well characterized, particularly in relation to process utilities. Eight vignettes of health states and daily activity restrictions related to each of the following RRMM therapies were prepared: no treatment, CAR T cell therapy with idecabtagene vicleucel (ide-cel), regular intravenous infusion, and oral administration. A face-to-face survey of healthy Japanese adults who were representative of the general population was conducted. The TTO method was used to evaluate each vignette and to generate utility scores for each treatment regimen. Three hundred and nineteen respondents participated in the survey (mean age: 44 years [range: 20–64]; female: 50%). Utility scores for no treatment, ide-cel, oral pomalidomide, and dexamethasone (Pd) therapy ranged from ∼0.7 to 0.8. Utility scores for regular intravenous infusion regimens ranged from 0.50 to 0.56. There was a difference of ∼0.2 between the utility scores for no treatment/ide-cel/oral administration and regular intravenous infusions. Differences in treatment administration across RRMM therapies showed a substantial impact on health state utilities. When quantifying the value of treatments, process utility gains should be considered as an independent factor in health technology assessments. [ABSTRACT FROM AUTHOR]

For patients with cartilage defects of the knee, a new biocompatible and in situ cross-linkable albumin-hyaluronan-based hydrogel has been developed for matrix-associated autologous chondrocyte implantation (M-ACI) – NOVOCART Inject plus (Ninject; TETEC AG, Reutlingen, Germany). We aimed to estimate the potential cost-effectiveness of NInject, that is not available on the market, yet compared to spheroids of human autologous matrix-associated chondrocytes (Spherox; CO.DON GmbH, Leipzig, Germany) and microfracture. An early Markov model was developed to estimate the cost-effectiveness in the United Kingdom (UK) from the payer perspective. Transition probabilities, response rates, utility values and costs were derived from literature. Since NInject has not yet been launched and no prices are available, its costs were assumed equal to those of Spherox. Cycle length was set at one year and the time horizon chosen was notional patients' remaining lifetime. Model robustness was evaluated with deterministic and probabilistic sensitivity analyses (DSA; PSA) and value of information analysis (VOIA). The Markov model was built using TreeAge Pro Healthcare. NInject was cost-effective compared to microfracture (ICER: ₤5,147) while Spherox was extendedly dominated. In sensitivity analyses, the ICER exceeded conventional WTP threshold of ₤20,000 only when the utility value after successful first treatment with NInject was decreased by 20% (ICER: ₤69,620). PSA corroborated the cost-effectiveness findings of NInject, compared to both alternatives, with probabilities of 60% of NInject undercutting the aforementioned WTP threshold and being the most cost-effective alternative. The VOIA revealed that obtaining additional evidence on the new technology will likely not be cost-effective for the UK National Health Service. This early Markov model showed that NInject is cost-effective for the treatment of articular cartilage defects in the knee, compared to Spherox and microfracture. However, as the final price of NInject has yet to be determined, the cost-effectiveness analysis performed in this study is provisional, assuming equal prices for NInject and Spherox. [ABSTRACT FROM AUTHOR]

Real-world evidence is a valuable source of information in healthcare. This study describes the challenges and successes during algorithm development to identify cancer cohorts and multi-agent chemotherapy regimens from claims data to perform a comparative effectiveness analysis of granulocyte colony stimulating factor (G-CSF) use. Using the Biologics and Biosimilars Collective Intelligence Consortium's Distributed Research Network, we iteratively developed and tested a de novo algorithm to accurately identify patients by cancer diagnosis, then extract chemotherapy and G-CSF administrations for a retrospective study of prophylactic G-CSF. After identifying patients with cancer and subsequent chemotherapy exposures, we observed only 12% of patients with cancer received chemotherapy, which is fewer than expected based on prior analyses. Therefore, we reversed the initial inclusion criteria to identify chemotherapy receipt, then prior cancer diagnosis, which increased the number of patients from 2,814 to 3,645, or 68% of patients receiving chemotherapy had diagnoses of interest. Additionally, we excluded patients with cancer diagnoses that differed from those of interest in the 183 days before the index date of G-CSF receipt, including early-stage cancers without G-CSF or chemotherapy exposure. By removing this criterion, we retained 77 patients who were previously excluded. Finally, we incorporated a 5-day window to identify all chemotherapy drugs administered (excluding oral prednisone and methotrexate, as these medications may be used for other non-malignant conditions) as patients may fill oral prescriptions days to weeks prior to infusion. This increased the number of patients with chemotherapy exposures of interest to 6,010. The final cohort of included patients, based on G-CSF exposure, increased from 420 from the initial algorithm to 886 using the final algorithm. Medications used for multiple indications, sensitivity and specificity of administrative codes, and relative timing of medication exposure must all be evaluated to identify patient cohorts receiving chemotherapy from claims data. [ABSTRACT FROM AUTHOR]

This retrospective, observational cohort study aimed to determine the burden of comorbidities, hospitalization, and healthcare costs among patients with non-alcoholic steatohepatitis (NASH) in the United States stratified by fibrosis-4 (FIB-4) or body mass index (BMI). Adults with NASH were identified in the Veradigm Health Insights Electronic Health Record Database and linked Komodo claims data. The index date was the earliest coded NASH diagnosis between 1 January 2016 and 31 December 2020 with valid FIB-4 and ≥6 months of database activity and continuous enrollment pre- and post-index. We excluded patients with viral hepatitis, alcohol-use disorder, or alcoholic liver disease. Patients were stratified by FIB-4: FIB-4 ≤ 0.95, 0.95 < FIB-4 ≤ 2.67, 2.67 < FIB-4 ≤ 4.12, FIB-4 > 4.12) or BMI (BMI <25, 25 ≤ BMI ≤30, BMI > 30). Multivariate analysis was used to assess the relationship of FIB-4 with costs and hospitalizations. Among 6,743 qualifying patients, index FIB-4 was ≤0.95 for 2,345 patents, 0.95–2.67 for 3,289 patients, 2.67–4.12 for 571 patients, and >4.12 for 538 patients (mean age 55.8 years; 62.9% female). Mean age, comorbidity burden, cardiovascular disease risk, and healthcare utilization increased with increasing FIB-4. Mean ± SD annual costs increased from $16,744±$53,810 to $34,667±$67,691 between the lowest and highest FIB-4 cohorts and were higher among patients with BMI <25 ($24,568±$81,250) than BMI >30 ($21,542±$61,490). A one-unit increase in FIB-4 at index was associated with a 3.4% (95%CI: 1.7%–5.2%) increase in mean total annual cost and an 11.6% (95%CI: 8.0%–15.3%) increased likelihood of hospitalization. A higher FIB-4 was associated with increased healthcare costs and risk of hospitalization in adults with NASH; however, even patients with FIB-4 ≤ 0.95 presented a significant burden. [ABSTRACT FROM AUTHOR]

Screening for non-valvular atrial fibrillation (NVAF) is key in identifying patients with undiagnosed disease who may be eligible for anticoagulation therapy. Understanding the economic value of screening is necessary to assess optimal strategies for payers and healthcare systems. We evaluated the cost effectiveness of opportunistic screening with handheld digital devices and pulse palpation, as well as targeted screening predictive algorithms for UK patients ≥75 years of age. A previously developed Markov cohort model was adapted to evaluate clinical and economic outcomes of opportunistic screening including pulse palpation, Zenicor (extended 14 days), KardiaMobile (extended), and two algorithms compared to no screening. Key model inputs including epidemiology estimates, screening effectiveness, and risks for medical events were derived from the STROKESTOP, ARISTOTLE studies, and published literature, and cost inputs were obtained from a UK national cost database. Health and cost outcomes, annually discounted at 3.5%, were reported for a cohort of 10,000 patients vs. no screening over a time horizon equivalent to a patient's lifetime, Analyses were performed from a UK National Health Services and personal social services perspective. Zenicor, pulse palpation, and KardiaMobile were dominant (providing better health outcomes at lower costs) vs. no screening; both algorithms were cost-effective vs. no screening, with incremental cost-effectiveness ratios per quality-adjusted life-year (QALY) of £1,040 and £1,166. Zenicor, pulse palpation, and KardiaMobile remained dominant options vs. no screening in all scenarios explored. Deterministic sensitivity analyses indicated long-term stroke care costs, prevalence of undiagnosed NVAF in patients 75–79 years of age, and clinical efficacy of anticoagulant on stroke prevention were the main drivers of the cost-effectiveness results. Screening for NVAF at ≥75 years of age could result in fewer NVAF-related strokes. NVAF screening is cost-effective and may be cost-saving depending on the program chosen. [ABSTRACT FROM AUTHOR]

In 2019, the prevalence of dialysis in Kuwait were 465 patient/million population, while the annual mortality rate among dialysis patients reached 12%. To improve resource allocation within the health care system, a cost-effectiveness model was conducted from a societal perspective to assess the cost-effectiveness of the use of dapagliflozin as an add-on-therapy against SoC (ramipril) among CKD patients with or without type-2 diabetes over their lifetime. A Markov process model was utilized to assess the cost-effectiveness of dapagliflozin + ramipril versus ramipril alone on a cohort of patients with an eGFR of 25 to 75 mL/min/1.73, with or without type-2 diabetes and a urinary ACR of 200 to 5,000 over their lifetime. The model included nine health states: (i) the six stages of CKD representing stages 1, 2, 3a, 3b, 4 and 5; (ii)ESRD, which represents RRT as dialysis or kidney transplant and (iii) death. Most of the clinical data were captured from the DAPA-CKD study. We assumed that the mortality risk of our study was similar to DAPA-CKD. The utility data were captured from different studies. Direct medical and indirect costs were captured from local data sources. Sensitivity analyses were conducted. The difference in QALY between dapagliflozin + ramipril versus ramipril was 0.2. The difference in cost between the two arms was KWD −4,120 (−USD25750). Dapagliflozin + ramipril generate better QALYs and lower costs than ramipril in CKD patients. Dapagliflozin improved the outcomes and generated cost savings in CKD patients. Adoption of dapagliflozin + ramipril is considered to be a cost saving option in addition to the improvement in QALYs in CKD patients with or without type-2 diabetes due to its nephroprotective effect, regardless of the aetiology of CKD, which eventually leads to reduction of dialysis and the transplantation cost burden on the Kuwaiti health care system. This study was focussed only on DAPA-CKD cohort. [ABSTRACT FROM AUTHOR]

People with recurrent epileptic seizures are typically treated with anti-seizure medications (ASMs). Around a third of epilepsy patients fail to achieve an adequate response to ASMs and may be eligible to receive vagus nerve stimulation (VNS) therapy for their drug-resistant epilepsy (DRE) if they are unsuited to surgery. VNS received approval from the United States (US) Food and Drug Administration agency. However, there has to date been no comprehensive cost effectiveness evaluation of VNS within the US setting. This study was designed, using a US Medicare perspective, to estimate costs and quality-adjusted life years (QALYs) associated with VNS as an adjunct to ongoing ASM therapy, compared to ASMs alone. We developed a cohort state transition model in Microsoft Excel, with four health states defined by different percentage reductions in seizure frequency, with a 3-month cycle and transition probabilities derived from published clinical trials and registry data. Sensitivity analyses were conducted to understand the impact of parameter uncertainty. Costs included the VNS device, placement, programming, battery changes, and removal; ASM therapy; adverse events associated with VNS (dyspnea, hoarseness, and cough); and costs associated with seizure burden (i.e. hospitalizations, emergency department visits, neurologist visits). Under base case assumptions, treatment with VNS was associated with a 0.385 QALY gain and a $109,678 saving per patient, when compared with ASM therapy alone. The incremental net monetary benefit (iNMB) was $128,903 at a threshold of $50,000 per QALY, with the positive iNMB indicating that VNS is a highly cost effective treatment. This result is explained by the modeled reduction in relative seizure frequency and associated reduction in healthcare resource use that the VNS group experienced. Sensitivity analyses supported this conclusion. VNS was evaluated as a cost effective addition to the current standard of care in the treatment of DRE in the US Medicare context. Anti-seizure medications (ASMs) are drugs commonly prescribed to people with epilepsy to help prevent seizures from reoccurring. But these drugs do not work for all people: around a third keep having seizures despite taking the medication—a condition called drug-resistant epilepsy (DRE). For such people, their main options involve trying different combinations of ASMs, having brain surgery, or having a medical device implanted. In the United States (US), vagus nerve stimulation (VNS) therapy is approved by the Food and Drug Administration agency for DRE patients who are still having focal onset seizures despite trying ASM therapy. Using methods defined by the US evaluation body, the Institute for Clinical and Economic Review, we made an economic model to assess how cost effective VNS would be as an add-on to ASM therapy. The evaluation utilizes a previously published model, which was updated to use costs, health-related quality of life, and mortality estimates relevant to the US Medicare setting. The analysis demonstrated that VNS could generate cost savings when used as an add-on ASM treatment in the US Medicare setting. VNS may reduce the number of seizures, and subsequently improve patient quality of life and result in substantially lower costs for Medicare (e.g. in emergency and hospital care for a person having a seizure). We tested uncertainties in our model using standard methods—these additional analyses allow us to conclude that VNS is highly likely to be a cost effective addition to the current standard of care for DRE treatment from a US perspective. [ABSTRACT FROM AUTHOR]

Advanced energy devices are commonly used in electrosurgery, including ultrasonic and advanced bipolar (ABP) devices. Smoke evacuation and reusable dispersive electrodes are also utilized during electrosurgery to improve staff and patient safety. This study assessed the budget impact of adopting a portfolio of Ethicon energy devices compared to devices from other manufacturers from a Spanish hospital perspective. The main analysis compared the Ethicon advanced energy device portfolio (ultrasonic and ABP devices) to Non-Ethicon advanced energy devices. It was assumed that 4,000 procedures using one advanced energy device each were performed annually, and the cost impact of operating room time, length of stay, and transfusions were considered. A probabilistic budget impact analysis with 10,000 iterations was conducted for generalizability to other hospitals in Spain and Europe. Secondary analysis assessed whether cost savings from the Ethicon advanced energy device portfolio could offset costs of adopting smoke evacuation and reusable dispersive electrodes (Full Ethicon energy portfolio). In the main analysis, the annual budget impact of introducing the Ethicon advanced energy device portfolio was cost saving in 79.8% of probabilistic iterations (mean: -€945,214; 95% credible interval [CrI]: -€3,242,710; €1,285,942) with a mean budget impact per procedure of -€236 (95% CrI: -€811; €321). In the secondary analysis, adding smoke evacuation and reusable dispersive electrodes was still cost saving in 75.3% of iterations compared to Non-Ethicon advanced energy devices (mean: -€778,208; 95% CrI: -€3,075,086; €1,464,728) with a mean budget impact per procedure of -€97 (95% CrI: -€384; €183). Savings resulted from differences in operating room time, length of hospital stay, and volume of disposable electrodes. Adopting Ethicon advanced energy devices demonstrated economic benefits compared to non-Ethicon devices. Introducing the advanced portfolio may improve surgical care quality and the full portfolio was cost saving while improving OR safety for staff and patients. This study created an economic model to calculate whether using modern electrical surgical tools with features to make cutting tissue and stopping bleeding faster and easier could save Spanish hospitals money. The electrical surgery tools from one manufacturer were compared to those from various other companies. Differences in how long surgery took to perform, how long patients stayed in hospital after their surgery, and how many blood transfusions they needed were considered in the model. The model was tested 10,000 times with random changes in the costs and settings used to be surer about the range of possible results. The results showed the devices from one manufacturer could save a Spanish hospital money in almost 80% of model runs and that savings worked out to €236 per surgery. In another analysis, savings were enough to cover the cost of introducing safety devices to remove surgical smoke from the operating room and reusable patient grounding electrodes that prevent some injuries potentially caused by small sticky electrodes. In conclusion, the model showed that Spanish hospitals may be able to save money by switching to the modern electrical surgery tools from Ethicon. [ABSTRACT FROM AUTHOR]

Several disease-modifying treatments (DMTs) for relapsing-remitting multiple sclerosis (RRMS) reduce relapse rates and slow disease progression. RRMS DMTs have varying efficacy and administration routes; DMTs prescribed first may not be the most effective on relapses or disease progression. Here, we aimed to quantify the benefit of initiating ofatumumab, a high-efficacy DMT, earlier in the treatment pathway. Aggregate data from a real-world cohort of patients with RRMS, who were eligible for dimethyl fumarate (DMF) or ofatumumab treatment within the UK National Health Service (N = 615), were used to produce a simulated patient cohort. The cohort was tracked through a discrete event simulation (DES) model, based on the Expanded Disability Status Scale (EDSS), with a lifetime time horizon. Outcomes assessed were: mean number of relapses, time to wheelchair (EDSS ≥7), and time to death. Two modeling approaches were used. The first compared outcomes between two treatment sequences (base case: ofatumumab to natalizumab versus DMF to ofatumumab). The second incorporated a time-specific delay of 1–5 years for switching from DMF to ofatumumab; the difference in outcomes as a function of increasing delay to ofatumumab are reported. Compared with delayed ofatumumab, fewer relapses and increased time to wheelchair were predicted for earlier ofatumumab in the treatment-sequence approach (mean relapses over the lifetime time horizon: 8.63 versus 9.00; time to wheelchair: 17.55 versus 16.60 years). Time to death was similar for both sequences. At Year 10, a numerically greater proportion of patients receiving earlier ofatumumab had mild disease (EDSS 0–3: 44.12% versus 40.06%). Greater differences, reflecting poorer outcomes, were predicted for relapses and time to wheelchair with increasing delays to ofatumumab treatment. The DES model provided a means by which the magnitude of benefit associated with earlier ofatumumab initiation could be quantified; fewer relapses and a prolonged time to wheelchair were predicted. [ABSTRACT FROM AUTHOR]

To estimate clinical events and evaluate the financial implications of introducing ferric carboxymaltose (FCM) to treat iron deficiency (ID) at discharge in patients hospitalized for acute heart failure (AHF) with left ventricular ejection fraction (LVEF) <50% in the UK, Switzerland and Italy. A decision analytic cost-offset model was developed to evaluate the costs associated with introducing FCM for all eligible patients in three countries compared to a world without FCM, over a five-year time horizon. Data from AFFIRM-AHF clinical trial were used to model clinical outcomes, using an established cohort state-transition Markov model. Country-specific prevalence estimates were derived using data from real-world studies to extrapolate number of events and consequent cost totals to the population at risk on a national scale. The cost-offset modeling demonstrated that FCM is projected to be a cost-saving intervention in all three country settings over a five-year time horizon. Savings were driven primarily by reduced hospitalizations and avoided cardiovascular deaths, with net cost savings of −£14,008,238, −CHF25,456,455 and −€105,295,146 incurred to the UK, Switzerland and Italy, respectively. Although AFFIRM-AHF was a multinational trial, efficacy data per country was not sufficiently large to enable country-specific analysis, therefore overall clinical parameters have been assumed to apply to all countries. This study provides further evidence of the potential cost savings achievable by treating ID with FCM at discharge in patients hospitalized for AHF with LVEF <50%. The value of FCM treatment within the healthcare systems of the UK, Switzerland and Italy was demonstrated even within a limited time frame of one year, with consistent cost savings indicated over a longer term. [ABSTRACT FROM AUTHOR]

Pimavanserin (PIM) is the only FDA-approved atypical antipsychotic (AAP) for hallucinations and delusions associated with Parkinson's disease psychosis (PDP). Comparative real-world analyses demonstrating its benefits are needed. To evaluate health care resource utilization (HCRU) outcomes among PDP patients treated with PIM vs. other-AAPs. Retrospective cohort analysis of Parts A, B, and D claims from 100% Medicare sample from 01 January 2013–31 December 2019 was conducted. PDP Patients initiating (i.e. index date) continuous monotherapy (PIM vs. other-AAPs) for ≥12-months during 01 January 2014–31 December 2018 without 12-months pre-index AAP use were selected after 1:1 propensity score matching (PSM) on 31 variables (sex, race, region, age, and 27 Elixhauser comorbidities). HCRU outcomes included: annual all-cause and psychiatric hospitalization (short-term stay, long-term stay, and SNF-stay [skilled nursing facility]) rates, annual all-cause and psychiatric-ER visit rates, mean per-patient-per-year (PPPY) hospitalizations, and average length of stay (ALOS). PIM and other-AAPs were compared using generalized linear models (GLM) controlled for demographic characteristics, comorbidities, coexisting-dementia, and coexisting insomnia. Of 12,164 PDP patients, 48.41% (n = 5,889) were female, and mean age was 77 (±8.14) years. Among 1:1 matched patients (n = 842 in each), 37.8% (n = 319) on PIM vs. 49.8% (n = 420) on other-AAPs (p <.05) reported ≥1 all-cause hospitalizations, respectively. Specifically, short-term and SNF-stay among PIM patients vs. other-AAPs were: 34% (n = 286) vs. 46.2% (n = 389) and 20.2% (n = 170) vs. 31.8% (n = 267) (p <.05), respectively. Similarly, 9.6% (n = 81) of PIM vs. 14.6% (n = 123) of other-AAPs patients had ≥1 psychiatric hospitalization (p <.05). Furthermore, ≥1 all-cause and psychiatric ER visit among PIM vs. other-AAPs were 61.6% (n = 519) vs. 69.4% (n = 584) and 5.2% (n = 43) vs. 10.2% (n = 86) (p <.05), respectively. PIM also had significantly lower ALOS, and mean PPPY short-term hospitalization and SNF-stays. In this analysis of PDP patients, PIM monotherapy resulted in nearly 12% and 7% lower all-cause hospitalizations and ER visits vs. other-AAPs. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea syndrome (OSAS) in children has become a major public health problem that affects the physical and mental growth of children. OSAS can result in adverse outcomes during growth and development, inhibiting the normal development of the metabolic, cardiovascular, and immune systems. OSAS is characterized by partial or complete obstruction of the upper airway, and prolonged obstruction that causes intermittent hypoxia and sleep fragmentation in children. The human microbiota is a complex community that is in dynamic equilibrium in the human body. Intermittent hypoxia and sleep fragmentation induced by childhood OSAS alter the composition of the gut microbiome. At the same time, changes in the gut microbiome affect sleep patterns in children through immunomodulatory and metabolic mechanisms, and induce further comorbidities, such as obesity, hypertension, and cardiovascular disease. This article discusses recent progress in research into the mechanisms of OSAS-induced changes in the gut microbiota and its pathophysiology in children. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to assess the effects of butylphthalide on cognitive deficiencies following sleep deprivation (SD).Methods: The influence of butylphthalide on cognitive function changes in SD-induced mice was evaluated. Nissl staining and HE staining were used to analyze the morphology changes of the hippocampal formation. The changes in cognitive function of SD-induced mice were detected by the Morris water maze. Inflammatory factors, apoptosis, and signal pathway-related proteins in the mice hippocampus were detected.Results: SD increased escape latency and path length for mice to reach the hidden platform, decreased the time and range of activity in the target area, and reduced the number and time for traversing the target area. Butylphthalide significantly improved the cognitive decline of SD-induced spatial exploration and learning/memory ability. Butylphthalide also decreased the degeneration of hippocampal neurone, neuronal apoptosis, and inflammatory factors in hippocampus tissue. In addition, butylphthalide activated the nuclear factor erythroid 2-related factor (Nrf2)/heme oxygenase 1 (HO-1) pathway.Conclusion: Butylphthalide alleviated SD-induced cognitive decline, neuronal apoptosis, and inflammation by activating Nrf2/HO-1 pathway. We suggested that butylphthalide may be a prospective candidate for the alleviation of cognitive deficit induced by SD. [ABSTRACT FROM AUTHOR]

Background: Acute diarrhea is the most frequent diagnosis among ill travelers. Sleep loss may weaken the body's defense against pathogens and increase susceptibility to infection. The relationship between sleep and infectious diarrhea has not been studied and was assessed utilizing data from a controlled human infection model (CHIM) for enterotoxigenic Escherichia coli (ETEC).Methods: During a CHIM assessing the efficacy of an immunoprophylactic targeting ETEC against moderate-to-severe diarrhea (MSD) following challenge, we measured sleep via actigraphy over an 8-day inpatient period. We hypothesized better sleep pre-challenge would predict illness symptomatology following challenge.Results: Among 57 participants (aged 34.4 ± 8.1 years, 64% male), there was no relationship between sleep metrics and incidence of MSD. However, longer total sleep time the night preceding ETEC challenge was associated with lower maximum 24 h diarrhea volume (B = -1.80, p = 0.01) and total diarrhea volume (B = -2.45, p = 0.01).Conclusions: This novel study showed that shorter sleep duration predicted diarrhea severity over the course of an ETEC infection. Future work should experimentally manipulate sleep to further clarify its impact on diarrhea-related outcomes for ETEC and other important enteric pathogens. [ABSTRACT FROM AUTHOR]