Prevalence, predictors and outcomes of potential drug-drug interactions in left ventricular failure: considerable factors for quality use of medicines

Hospitalized patients with left ventricular failure (LVF) are at high risk for potential drug-drug interactions (pDDIs) and its related adverse effects owing to multiple risk factors such as old age, comorbidities and polypharmacy. This cross-sectional study conducted in two tertiary care hospitals aim to identify frequency, levels and predictors of pDDIs in LVF patients. Data about patients’ demographic, hospital stay, medication therapy, sign/symptoms and laboratory test results were collected for 385 patients with LVF. Micromedex Drug-Reax® was used to screen patients’ medication profiles for pDDIs. Overall prevalence and severity-wise prevalence of pDDIs were identified. Chisquare test was performed for comparative analysis of various variables. Logistic regression was applied to determine the odds-ratios (OR) for predictors of pDDIs. The prevalence of pDDIs was 96.4% (n=371). Overall 335 drug-interacting pairs were detected, which were presented in a total of 2870 pDDIs. Majority of pDDIs were of major- (48.9%) and moderate-severity (47.5%). Logistic regression analysis shows significant association of >6 all types of pDDIs with >12 drugs as compared with <8 drugs (OR=16.5; p=<0.001). Likewise, there was a significant association of >4 majorpDDIs with men as compared with female (OR=1.9; p=0.007) and >12 drugs as compared with <8 drugs (OR=10.9; p=<0.001). Hypotension (n=57), impaired renal function (23) and increased blood pressure (22) were the most frequent adverse outcomes associated with pDDIs. This study shows high prevalence of pDDIs in LVF patients. Majority of pDDIs were of major- and moderate-severity. Male patients and those prescribed greater number of medicines were more exposed to major-pDDIs

Heat generation effects on maxwell nanofluid passing over an oscillating vertical plate

This article investigates the flow of Maxwell nanofluid over an oscillating plate with copper nanoparticles and kerosene oil as a base fluid. Novel aspects of heat generation, free convection and thermophysical properties of nanofluids are given special attention in this research. Revised model for passive control of nanoparticle volume fraction at the plate is used in this study. The formulated differential system is solved analytically using Laplace transform technique. The solutions acquired for momentum, temperature and shear stress are greatly influenced with the variation of the volume fraction and Maxwell parameter. The computational software MathCAD-15 has been used for plotting the graphs

Cytotoxicity against A549 Human Lung Cancer Cell Line via the Mitochondrial Membrane Potential and Nuclear Condensation Effects of Nepeta paulsenii Briq., a Perennial Herb

The genus Nepeta belongs to the largest Lamiaceae family, with 300 species, which are distributed throughout the various regions of Africa, Asia, India, and America. Along with other plant families distinguished by their medicinal and therapeutic values, the Nepeta genus of Lameaceae remains relatively valuable. Hence, the phytochemicals of N. paulsenii Briq. were extracted using different plant parts, i.e., leaves, stem, roots, flowers, and the whole plant by using various solvents (ethanol, water, and ethyl acetate), obtaining 15 fractions. Each extract of dried plant material was analyzed by FT-IR and GC-MS to identify the chemical constituents. The cytotoxicity of each fraction was analyzed by MTT assay and mitochondrial membrane potential and nuclear condensation assays against lung cancer cells. Among the ethyl acetate and ethanolic extracts, the flowers showed the best results, with IC50 values of 51.57 μg/mL and 50.58 μg/mL, respectively. In contrast, among the water extracts of the various plant segments, the stem showed the best results, with an IC50 value of 123.80 μg/mL. 5-flourouracil was used as the standard drug, providing an IC50 value of 83.62 μg/mL. The Hoechst 33342 stain results indicated apoptotic features, i.e., chromatin dissolution and broken down, fragmented, and crescent-shaped nuclei. The ethanolic extracts of the flowers showed more pronounced apoptotic effects on the cells. The mitochondrial membrane potential indicated that rhodamine 123 fluorescence signals suppressed mitochondrial potential due to the treatment with the extracts. Again, the apoptotic index of the ethanolic extract of the flowers remained the highest. Hence it can be concluded that the flower part of N. paulsenii Briq. was found to be the most active against the A459 human lung cancer cell line

Synergistic effects of H\u3csub\u3e2\u3c/sub\u3eO\u3csub\u3e2\u3c/sub\u3e and S\u3csub\u3e2\u3c/sub\u3eO\u3csub\u3e8\u3c/sub\u3e\u3csup\u3e2−\u3c/sup\u3e in the gamma radiation induced degradation of congo-red dye: Kinetics and toxicities evaluation

© 2019 Elsevier B.V. Gamma radiation has received increasing attention due to their high potential in degradation of recalcitrant pollutants. Thus in the present study, gamma radiation was used for degradation of congo-red (CR) dye, a highly toxic and carcinogenic pollutant, in the presence of H2O2 and S2O82−. The CR was significantly degraded by gamma radiation (i.e., 53%), however, presence of H2O2 and S2O82− promoted degradation of CR to 98 and 87%, respectively, at 1184 Gy absorbed dose. The radical scavengers and electron spin resonance studies revealed that gamma radiation decompose H2O2 and S2O82− into [rad]OH and SO4[rad]− and both [rad]OH and SO4[rad]− caused degradation of CR. The CR showed high reactivity, i.e., 3.25 × 109 and 8.50 × 108 M−1 s−1 with [rad]OH and SO4[rad]−, respectively, and removal of CR was inhibited in the presence of [rad]OH and SO4[rad]− scavengers. The removal of CR was promoted with elevating initial concentrations of H2O2 and S2O82− and decreasing initial concentrations of CR. pH of aqueous solution also significantly influenced removal of the dye. The proposed degradation pathways of CR were established from the [rad]OH mediated degradation of CR and nature of identified degradation products. The greater mineralization of CR, formation of small molecular mass degradation product, and decline in concentration of acetate after extended treatment suggest the gamma-ray mediated peroxide based process to be a promising alternative for potential degradation of CR

Fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin with gemtuzumab ozogamicin improves event-free survival in younger patients with newly diagnosed aml and overall survival in patients with npm1 and flt3 mutations

Purpose To determine the optimal induction chemotherapy regimen for younger adults with newly diagnosed AML without known adverse risk cytogenetics. Patients and Methods One thousand thirty-three patients were randomly assigned to intensified (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin [FLAG-Ida]) or standard (daunorubicin and Ara-C [DA]) induction chemotherapy, with one or two doses of gemtuzumab ozogamicin (GO). The primary end point was overall survival (OS). Results There was no difference in remission rate after two courses between FLAG-Ida + GO and DA + GO (complete remission [CR] + CR with incomplete hematologic recovery 93% v 91%) or in day 60 mortality (4.3% v 4.6%). There was no difference in OS (66% v 63%; P = .41); however, the risk of relapse was lower with FLAG-Ida + GO (24% v 41%; P < .001) and 3-year event-free survival was higher (57% v 45%; P < .001). In patients with an NPM1 mutation (30%), 3-year OS was significantly higher with FLAG-Ida + GO (82% v 64%; P = .005). NPM1 measurable residual disease (MRD) clearance was also greater, with 88% versus 77% becoming MRD-negative in peripheral blood after cycle 2 (P = .02). Three-year OS was also higher in patients with a FLT3 mutation (64% v 54%; P = .047). Fewer transplants were performed in patients receiving FLAG-Ida + GO (238 v 278; P = .02). There was no difference in outcome according to the number of GO doses, although NPM1 MRD clearance was higher with two doses in the DA arm. Patients with core binding factor AML treated with DA and one dose of GO had a 3-year OS of 96% with no survival benefit from FLAG-Ida + GO. Conclusion Overall, FLAG-Ida + GO significantly reduced relapse without improving OS. However, exploratory analyses show that patients with NPM1 and FLT3 mutations had substantial improvements in OS. By contrast, in patients with core binding factor AML, outcomes were excellent with DA + GO with no FLAG-Ida benefit

The global retinoblastoma outcome study : a prospective, cluster-based analysis of 4064 patients from 149 countries

DATA SHARING : The study data will become available online once all analyses are complete.BACKGROUND : Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. METHODS : We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1, 2017, and Dec 31, 2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. FINDINGS : The cohort included 4064 children from 149 countries. The median age at diagnosis was 23·2 months (IQR 11·0–36·5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0·8%) of 636 children from high-income countries, 55 (5·4%) of 1027 children from upper-middle-income countries, 342 (19·7%) of 1738 children from lower-middle-income countries, and 196 (42·9%) of 457 children from low-income countries. Enucleation surgery was available for all children and intravenous chemotherapy was available for 4014 (98·8%) of 4064 children. The 3-year survival rate was 99·5% (95% CI 98·8–100·0) for children from high-income countries, 91·2% (89·5–93·0) for children from upper-middle-income countries, 80·3% (78·3–82·3) for children from lower-middle-income countries, and 57·3% (52·1-63·0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16·67; 95% CI 4·76–50·00), cT4 advanced tumour compared to cT1 (8·98; 4·44–18·18), and older age at diagnosis in children up to 3 years (1·38 per year; 1·23–1·56). For children aged 3–7 years, the mortality risk decreased slightly (p=0·0104 for the change in slope). INTERPRETATION : This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes.The Queen Elizabeth Diamond Jubilee Trust and the Wellcome Trust.https://www.thelancet.com/journals/langlo/homeam2023Paediatrics and Child Healt

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Exact Solution for Heat Transfer Free Convection Flow of Maxwell Nanofluids with Graphene Nanoparticles

This article focuses on the flow of Maxwell nanofluids with graphene nanoparticles over a vertical plate (static) with constant wall temperature. Possessing high thermal conductivity, engine oil is useful to be chosen as base fluid with free convection. The problem is modelled in terms of PDE’s with boundary conditions. Some suitable non-dimensional variables are interposed to transform the governing equations into dimensionless form. The generated equations are solved via Laplace transform technique. Exact solutions are evaluated for velocity and temperature. These solutions are significantly controlled by some parameters involved. Temperature rises with elevation in volume fraction while Velocity decreases with increment in volume fraction. A comparison with previous published results are established and discussed. Moreover, a detailed discussion is made for influence of volume fraction on the flow and heat profile

Heat Transfer Enhancement in Free Convection Flow of CNTs Maxwell Nanofluids with Four Different Types of Molecular Liquids

This article investigates heat transfer enhancement in free convection flow of Maxwell nanofluids with carbon nanotubes (CNTs) over a vertically static plate with constant wall temperature. Two kinds of CNTs i.e. single walls carbon nanotubes (SWCNTs) and multiple walls carbon nanotubes (MWCNTs) are suspended in four different types of base liquids (Kerosene oil, Engine oil, water and ethylene glycol). Kerosene oil-based nanofluids are given a special consideration due to their higher thermal conductivities, unique properties and applications. The problem is modelled in terms of PDE’s with initial and boundary conditions. Some relevant non-dimensional variables are inserted in order to transmute the governing problem into dimensionless form. The resulting problem is solved via Laplace transform technique and exact solutions for velocity, shear stress and temperature are acquired. These solutions are significantly controlled by the variations of parameters including the relaxation time, Prandtl number, Grashof number and nanoparticles volume fraction. Velocity and temperature increases with elevation in Grashof number while Shear stress minimizes with increasing Maxwell parameter. A comparison between SWCNTs and MWCNTs in each case is made. Moreover, a graph showing the comparison amongst four different types of nanofluids for both CNTs is also plotted

Casson Model of MHD Flow of SA-Based Hybrid Nanofluid Using Caputo Time-Fractional Models

In this paper MHD flow of Casson hybrid nanofluids are investigated with Caputo time-fractional derivative. Alumina (Al) and copper (Cu) are used as nanoparticles in this study with heat, mass transfer and MHD flow over a vertical channel in a porous medium. The problem is modeled using Caputo fractional derivatives and thermophysical properties of hybrid nanoparticles. The influence of concerned parameters is investigated physically and graphically on the heat, concentration and flow. The effect of volume fraction on thermal conductivity of hybrid nanofluids is observed