Increase In Dose Research Articles

A Pilot Project to Implement a Pharmacist-Managed Remote Blood Pressure Monitoring Service

Background: Clinicians often hesitate to adjust antihypertensive medications based solely on clinic blood pressure (BP) readings. Limitations to obtaining home readings include access to sphygmomanometers and ability to provide accurate, reliable readings upon follow-up. Objective: This study examined whether an online platform linked to remote BP monitoring improved BP management and facilitated effective clinical interventions by pharmacists. Methods: Thirty patients with uncontrolled hypertension were enrolled and provided a remote BP monitor for home use. BP data downloaded to an online platform were monitored by two clinic pharmacists. Daily BP checks were requested (up to twice daily), and pharmacists called patients approximately weekly for 6 months. Through approved protocols, pharmacists individualized interventions to improve patient care. Descriptive statistics were used for demographic and clinical data. Results: The average systolic BP reduction was 39 mmHg (IQR = 17-52.5) for the 21 patients included in analysis. A target BP <140/<90 was achieved by 67%, and 76% had improved BP control. Patients utilized the cuff 2-4 times (n = 10) or >5 times weekly (n = 11). Through 261 patient contact attempts, the pharmacists requested more BP checks (n = 62), changed medications (n = 57), or provided non-pharmacologic counseling (n = 24) most often. Medication changes commonly included dose increases (n = 35) and additional agents (n = 17) for BP control. Spironolactone (n = 5) and thiazide diuretics (n = 5) were the most added medications. Conclusions: Most patients were willing to check their BP when provided with devices. The majority achieved a clinically significant decrease in home BP readings, demonstrating that pharmacist-driven home-monitoring programs can improve the optimization of hypertension regimens.

Pharmacokinetics of nano- and microcrystal formulations of low solubility compounds after intramuscular injection to mice.

The aim of this study was to investigate the pharmacokinetics (PK) of poorly soluble compounds when administered intramuscularly (i.m.) as crystalline particles of different sizes. Three uncharged compounds (griseofulvin, AZ'72, and AZ'07) with varying aqueous solubility were dosed to mice at 10 and 50mg/kg as nano- and microparticle formulations. The PK of the compounds was evaluated. The smaller particles of the drugs resulted in higher maximum plasma concentration (Cmax) and area under the plasma concentration-time profile (AUC) at 50mg/kg. There was a dose-proportional increase in AUC but less than dose dose-proportional increase in Cmax. The evaluation at 10mg/kg was more complex as increased exposure for nanoparticles was only observed for griseofulvin which has the highest solubility. In addition, there was an increase in half-life with an increase in dose. This study highlights that general expectations based on in vitro dissolution (i.e. that smaller particles dissolve faster than larger particles when surrounded by liquid) do not always translate to in vivo and demonstrates the importance of understanding the physicochemical properties of the drug, the characteristics of the formulations and the microphysiology at the delivery site.

Combinatory effect of ALA-PDT and itraconazole in the treatment of cutaneous protothecosis

BackgroundAs a rare subcutaneous infection, protothecosis is easily misdiagnosed. Similar to other subcutaneous infection, there is no unified standard for treatment, for cases not suitable for surgery, clinicians often use antifungal drugs based on their experience, and the course of treatment varies from several months to several years. Based on the fact that there are few relevant materials and researches on photodynamic therapy (PDT), we conducted a study based on a clinical case that used oral itraconazole combined with 5-aminolevylinic acid photodynamic therapy (ALA-PDT) to treat a patient with cutaneous protothecosis caused by Prototheca wicherhamii. MethodsDifferent concentrations of ALA and different light doses were used to investigate the effects of ALA-PDT on the growth inhibition of P. wickerhamii in vitro with Colony-counting Methods. And we used transmission electron microscopy (TEM) to visualize the structural changes and the effects of ALA-PDT treating on cellular structures of the P. wickerhamii. Futher, we performed the susceptibility test of P. wickerhamii to itraconazole before and after ALA-PDT in vitro. ResultsWe have successfully treated a patient with cutaneous protothecosis caused by P. wickerhamii by using combination therapy in a total of 9-week course of treatment. In vitro, ALA-PDT can inhibit the growth of P. wickerhamii when the ALA concentration was 5 mg/mL (P < 0.01), and this effect became stronger as the concentration of ALA or light dose is increased. Using TEM, we confirmed that ALA-PDT can disrupt the cell wall structure and partition structure of P. wickerhamii, which may contribute to its inhibitory effect. Further studies showed that the MIC of itraconazole for P. wickerhamii was decreased after ALA-PDT. ConclusionsALA-PDT combined with oral itraconazole can be used to treat cutaneous protothecosis. Accordingly, ALA-PDT can destroy the cell wall and partition structure of P. wickerhamii leading to an inhibitory effect on it in vitro, and the effect is enhanced with the increase of ALA concentration and light dose. Also, the sensitivity of P. wickerhamii to itraconazole is observed increased after ALA-PDT. So our study provides a theoretical basis for the promising treatment against cutaneus protothecosis.

Preparation & characterization of polyvinyl alcohol/thymol blue composites gel and films for low radiation dosimetry

BackgroundExposure to low radiation has been indispensable due to it is necessity in radiography and it is induced potential effects in patients and radiology staff. Hence the measurement and detection became inevitable for radiation practitioners and the patients. The study aimed to present the synthesis of polyvinyl alcohol gel doped with Thymol Blue dye (PVA/TB) as gel and films for low radiation dosimetry. MethodThe polymer was prepared under controlled parameters (PVA 5%, temperature 80 °C, dopped with 0.01, 0.03, 0.05, 0.07, 0.09 mw of TB). The formed gel and films were irradiated with x-ray as: 0, 2, 4, 6, 8, 10 mGy. ResultsGel and films showed color quenching from yellow to light yellow as the radiation dose increased, as well as gradual significant (R2 = 0.97) reduction in optical density for all concentration (0.01, 0.02–0.09 mw of TB). The UV-spectroscope for (PVA/TB0.01mw) gel showed absorbance peaks at λ = 435, 326 and 279 nm, that decreased significantly (R2 = 0.97) as the radiation dose increases. And XRD for (PVA/TB0.01 mw) reveals the crystallinity of PVA at 2 thetas = 19.5° which increased to 40.5% at 10 mGy. FTIR revealed the chemical bonds with relevant intensities (CH (725.1–781 & 3030 cm−1), C – C (883.2 & 1170.6 cm−1), C – O (1063- 1096 cm−1), CH2 (1357.6 cm−1 wagging, 2879.2 cm−1 alkyl stretch), C = C (1623.8–1651.5 cm−1), C = O (1681.6–1683.6 cm−1), C – OH (3288 cm−1)) that decreased as the radiation dose increased and new radiogenic bonds at vibrational bands 1063–1096 cm−1 referring to C – O – C of Polysaccharide's pyranose and at 2125.1 cm−1 for C ≡ C alkenyl). ConclusionBoth forms of PVA/TB films and gel showed feasibility and applicability for radiation detection and measurement.

Toxicological evaluation of combination products containing imidacloprid, moxidectin and pyriproxyfen

The purpose of the research is to investigate subacute cutaneous toxicity in rats, allergenic properties in guinea pigs and tolerance of increased doses of drugs based on imidacloprid, moxidectin and pyriproxyfen by dogs and cats of different age groups.Materials and methods. Toxicological studies (subacute cutaneous toxicity, study of allergenic properties) were conducted in the vivarium of the All-Russian Research Institute of Plant Protection, a branch of the Federal Scientific Center for Experimental Veterinary Medicine of the Russian Academy of Sciences, on male rats and guinea pigs. Experiments on the tolerance of drugs by target animal species (dogs, cats) were conducted in the Podolsk department of the All-Russian Research Institute of Plant Protection. The choice of doses, frequency and methods of administration of the studied drugs were determined in accordance with the Guidelines for Experimental (Preclinical) Study of New Pharmacological Substances. All doses were calculated for the drug taking into account the density (1.08 g/cm3).Results and discussion. When studying the acute cutaneous toxicity of the drug on rats, LD50 exceeded the maximum possible dose of 10 000 mg/kg (hazard class 4 according to GOST 12.1.007-76). In a subacute experiment on rats, it was established that doses of 1000 and 500 mg/kg are ineffective (safe), the threshold and toxic doses could not be established. These drugs, when treating animals 8 times with an interval of 3 days in a three- and five-fold increase in the maximum therapeutic dose during the experimental period, did not have a negative effect on the general condition of the animals, their physiological status and behavior; no statistically significant changes in the morphological and biochemical parameters of the blood, physicochemical parameters of urine were noted in animals from the experimental groups compared to the control. However, in one adult dog from the second experimental group, which was used a five-fold increase in the maximum therapeutic dose of the drug, depression was noted on the 20th day of the experiment. The physiological state of the animal returned to normal within 24 hours voluntarily without the use of symptomatic therapy.

Research on the Stability and Response of Food Packaging Polystyrene Resin Materials to γ-ray Irradiation.

Radiation stability of food packaging materials is the key to ensuring food quality. In this study, 60Co γ-ray was selected to investigate the radiation resistance of food packaging polystyrene (PS) resin material, although the FTIR analysis showed that the intensity of several peaks decreased slightly. The gel permeation chromatography (GPC) results displayed that the value of peak molecular weight (Mp) of PS went from 2.68 × 105 g/mol down to 2.22 × 105 g/mol. Moreover, the residual mass (Res) of PS increased from 7.208 to 30.23%, indicating that the tendency of coking of PS was stronger after irradiation. In addition, the peak intensities of the three main pyrolysis products -CH2-, CH4, and CH2=CH2 increased by more than 30% compared to unirradiated PS, and a large number of them were detected in the whole pyrolysis process. Moreover, mechanical property analysis finds that both breaking strength and elongation data increased before irradiation dose of 50 kGy, then, decreased sharply with further increase of irradiation dose. The theoretical bond order analysis confirmed that the tertiary carbon bond attaching the benzene ring had the lowest bond energy. This study can give helpful guidance when using PS for food packing materials.

On the response of the CR-39 NTD to low doses of gamma rays using optical and photoluminescence spectroscopy

In this work, the response of the CR-39 nuclear track detector (NTD) exposed to different low doses of gamma rays was investigated using UV–Vis and photoluminescence spectroscopy. Five NTDs of CR-39 were irradiated with low gamma-ray doses ranging from 10 to 120 kGy using a60Co source. The dose of gamma rays correlates with red shift in the absorption spectra of a gamma-irradiated CR-39 detector. As the gamma dose increases, the indirect and direct energy band gaps, as well as Urbach energy, decrease gradually. However, the decrease in the indirect optical band gap is greater than the decrease in the direct band gap. The observed spectra of the CR-39 detector after being irradiated with different doses of γ-rays showed an acceptable variation in photoluminescence (PL) emission spectra generated by a well-defined excitation wavelength of 290 nm. Starting at 45 kGy dose, the integrated area of the photoluminescence peak increases and tends to saturate, whereas the photoluminescence peak height is linearly correlated with the gamma dose with high sensitivity, which is 53.1 ± 6.3 CPS. kGy−1. According to the current findings, photoluminescence (PL) spectroscopy has a greater sensitivity than UV–Vis spectroscopy for measuring the response of the CR-39 detector to gamma rays in the dose range of 10–120 kGy. The results reflected a potential possibility of using the CR-39 detector in dosimetric applications of low gamma ray doses through the high resolution achieved by photoluminescence (PL) and UV–Vis spectroscopy.

Abstract P327: Comparing the Blood Pressure Response to Antihypertensive Treatment Intensification and Dose Increase to No Action for Uncontrolled Hypertension

Background: The addition of a new antihypertension medication class (CA) or dose increase (DI) in patients with hypertension (HTN) is relatively infrequent when HTN is uncontrolled (blood pressure [BP, mmHg] ≥ 140/90) during outpatient visits. We compared systolic (S)BP changes following CA, DI, or no medication changes for uncontrolled BP. Methods: A patient cohort from 6 diverse healthcare organizations, engaged in a quality improvement program, was identified with previously diagnosed HTN. Uncontrolled outpatient SBP measurements observed at participating program sites were compared to follow-up measurements within 7 to 120 days for evaluating SBP change. ANCOVA and linear regression analyses were used to control clinical and demographic covariates and assess differences in SBP change following treatment decision. Results: A prospective cohort of 124,068 patients with HTN spanning 280,937 events was identified, mean age 63.3 ± 13.9. Class addition reduced SBP 2.0 mmHg (95% CI, 1.81 – 2.24), whereas dose increase did not lower SBP [-0.07 (95% CI, -0.31, 0.16)]. Conclusion: In this study, CA lowered BP modestly, whereas DI appeared ineffective. Since patients were not randomized, our results may under-estimate the effects of CA and DI on BP, i.e., clinicians may have expected a greater decline of SBP than simply regression to the mean for patients with uncontrolled hypertension in the absence of DI or TI. Our data are consistent with reports that CA has a greater effect to lower BP than DI. Our findings also highlight some challenges of interpreting real world data compared to randomized clinical trials.

Pathophysiologic Vasodilation in Cardiogenic Shock and Its Impact on Mortality.

Cardiogenic shock (CS) mortality remains near 40%. In addition to inadequate cardiac output, patients with severe CS may exhibit vasodilation. We aimed to examine the prevalence and consequences of vasodilation in CS. We analyzed all patients hospitalized at a CS referral center who were diagnosed with CS stages B to E and did not have concurrent sepsis or recent cardiac surgery. Vasodilation was defined by lower systemic vascular resistance (SVR), higher norepinephrine equivalent dose, or a blunted SVR response to pressors. Threshold SVR values were determined by their relation to 14-day mortality in spline models. The primary outcome was death within 14 days of CS onset in multivariable-adjusted Cox models. This study included 713 patients with a mean age of 60 years and 27% females; 14-day mortality was 28%, and 38% were vasodilated. The median SVR was 1308 dynes•s•cm-5 (interquartile range, 870-1652), median norepinephrine equivalent was 0.11 µg/kg per minute (interquartile range, 0-0.2), and 28% had a blunted pressor response. Each 100-dynes•s•cm-5 decrease in SVR below 800 was associated with 20% higher mortality (adjusted hazard ratio, 1.23; P=0.004). Each 0.1-µg/kg per minute increase in norepinephrine equivalent dose was associated with 15% higher mortality (adjusted hazard ratio, 1.12; P<0.001). A blunted pressor response was associated with a nearly 2-fold mortality increase (adjusted hazard ratio, 1.74; P=0.003). Pathophysiologic vasodilation is prevalent in CS and independently associated with an increased risk of death. CS vasodilation can be identified by SVR <800 dynes•s•cm-5, high doses of pressors, or a blunted SVR response to pressors. Additional studies exploring mechanisms and treatments for CS vasodilation are needed.

A lung SBRT treatment planning technique to focus high dose on gross disease

This study investigated a straightforward treatment planning technique for definitive stereotactic body radiation therapy (SBRT) for patients with early-stage lung cancer aimed at increasing dose to gross disease by strategically penalizing the normal tissue objective (NTO) in the EclipseTM treatment planning system. Twenty-five SBRT cases were replanned to 50 Gy in 5 fractions using static and dynamic NTO methods (50 plans total). The NTO had a start dose of 100% at the target border, end dose of 20%, fall-off rate of 0.4/mm, and a priority of 150. For the static NTO plans, a lower planning target volume (PTV) objective was placed at 52 Gy with a priority of 100. Maximum dose was not penalized. Optimization was performed without user interaction. In contrast, the planner incrementally increased the priority of the NTO on the dynamic NTO plans until 95% of the target volume was covered by the prescription dose. Further, the dynamic NTO plans used both PTV lower and upper objectives at 63-64 Gy with priorities of 50. Maximum dose was penalized to ensure that the hot spot was within ± 2% of the static NTO global maximum dose. Following optimization, all plans were normalized so that the prescription dose covered 95% of the PTV. Plans were scored based on RTOG 0813 criteria, and dose to the internal target volume (ITV) and PTV was evaluated. The Wilcoxon signed-rank test (threshold = 0.05) was used to evaluate differences between the static and dynamic NTO plans. All plans met RTOG 0813 planning guidelines. In comparison to the static NTO plans, the dynamic NTO plans exhibited statistically significant increases in PTV mean dose, ITV mean dose, and PTV-ITV mean dose. Notably, the dynamic NTO plans more effectively concentrated the high dose on gross disease at the center of the PTV. As compared to the static NTO plans, the mean dose was 4.6 Gy higher in the ITV while only 1.3 Gy higher in the PTV-ITV rind of the dynamic NTO plans. Global maximum doses were similar. There were some small yet statistically significant differences in dose conformity between plan types. Furthermore, the dynamic NTO plans demonstrated a significant reduction in total monitor units (MU). This study demonstrated an efficient optimization strategy for lung SBRT plans that concentrates the highest dose in the gross disease, which may improve local control.

Abstract P117: Provider Concordance to the Current 2017 High Blood Pressure (BP) Clinical Practice Guidelines and Patient Blood Pressure Control

Introduction: The AHA/ACC 2017 High BP guidelines introduced key changes, compared to previous guidelines, including a new hypertension definition (≥130/80 mm Hg) and lower medication thresholds for patients at cardiovascular risk. The impact of provider adherence to these guidelines on patient BP control has not been fully explored. Methods: We identified 3,749 new stage 1 hypertension patients (7,214 visits) and 11,013 new stage 2 hypertension patients (33,321 visits), aged ≥18, from the Vanderbilt University Medical Center database. We scrutinized outpatient BP levels, prescribed medications, follow-up visits, lab results, demographics, comorbid conditions, and physician notes from January 2018 to December 2022. This data was compared to hypertension treatment criteria developed from the 2017 guidelines that was validated by six hypertension experts. Active primary care patients (with 1 visit per year) were included. Mixed-effects Poisson regression and mixed-effects linear regression examined the relationship between guideline adherence and controlled BP (&lt;130/80 mm Hg) and continuous BP, respectively. Results: Among stage 1 hypertension visits, 12.2% were treated with at least one antihypertensive drug according to guidelines, resulting in a 13% increase in BP control and a reduction in systolic BP by 2.02 mm Hg. For stage 2 hypertension visits, 26% received treatment with at least two first-line antihypertensive drug classes, leading to a 45% increase in BP control and reductions in systolic and diastolic BP by 3.79 mm Hg and 1.93 mm Hg, respectively. No significant difference in BP control was observed among stage 2 patients treated with two versus one first-line drug. Adherence to follow-up guidelines resulted in a 24% improvement in BP control for stage 1 patients and stage 2 patients when their follow-up visit occurred within 1 month. Subsequent follow-up visits within 1-month improved BP control by 34% if BP was not controlled previously. Additionally, 42.4% of patients with uncontrolled BP for 1 month received an increase in medication dose or a change/addition of medication class and showed a 7% increase in BP control within next month. Conclusion: Provider adherence to recommended antihypertensive drug treatment guidelines (12%-26%), follow-up assessments guidelines (29%-37%), and treatment intensification (42.4%) were poor. However, patients treated according to the guidelines showed significant improved BP control.

Agranulocytosis Induced by Overdosage of Mercaptopurine: A Case Report

Drug-induced agranulocytosis (DIAG) is a rare but potentially fatal hematological complication. Thiopurines, such as mercaptopurine (6-MP), are widely used in the treatment of chronic inflammatory bowel diseases (IBD), but can cause myelotoxicity due to the accumulation of active metabolites. We report the case of a 48-year-old woman with ulcerative colitis who developed severe agranulocytosis following an accidental overdose of 6-MP. The patient presented with febrile pancytopenia with a neutrophil count of 0.04 G/L. Bone marrow examination revealed normal cellularity with an inversion of the maturation pyramid of the granulocyte lineage. A treatment combining growth factors (filgrastim) and antibiotics (tazobactam) was initiated, leading to progressive improvement over 5 weeks. The toxicity of 6-MP is mainly due to the accumulation of 6-thioguanine nucleotides (6-TGN). The polymorphism of the gene encoding the enzyme thiopurine S-methyltransferase (TPMT) can influence the risk of myelotoxicity. Two strategies are proposed to minimize this risk: evaluation of TPMT activity with dosage adjustment, or regular monitoring of blood counts with gradual dose increase. This case highlights the importance of rigorous biological monitoring when initiating 6-MP treatment, regardless of the TPMT test. Increased vigilance is necessary when using immunosuppressive drugs in the treatment of IBD to optimize efficacy and minimize toxicity.

Hemodynamic Collapse After Intubation in Critical Care Transport

Objectives The aim of this study was to describe the incidence of and modifiable risk factors for post intubation hemodynamic collapse in prehospital and interfacility critical care transport. Methods Single center retrospective chart review of adult patients (≥18 years) intubated by a critical care transport team between January 2017 and May 2023. The primary outcome was incidence of hemodynamic collapse (systolic blood pressure <90 mmHg for greater than 30 min, new vasopressor requirement, vasopressor dose increase, fluid bolus of >15 mL/kg, systolic blood pressure <65 mmHg at least once, or cardiac arrest). Secondary outcomes included post intubation hypoxia, as well as association of hemodynamic collapse with potentially modifiable risk factors including pre intubation shock index, pre intubation heart rate, pre intubation systolic blood pressure, and induction agent. Results Three hundred and thirty-three patients were included. Ninety-seven (29.1%) patients experienced hemodynamic collapse and 36 (10.8%) of patients experienced life threatening hemodynamic collapse. Pre intubation shock index >1 (OR 3.18, 95% CI 1.15–8.74) was associated with post intubation hemodynamic collapse. Choice of induction agent, fluid bolus prior to intubation, location of intubation, presence of traumatic injury, and age were not correlated with risk of hemodynamic collapse. The number of intubation attempts and methods of intubation were similar between groups. Conclusions Hemodynamic collapse and life-threatening hemodynamic collapse after intubation occurred frequently in this critical care transport cohort. Shock index greater than one was associated with significantly higher risk of hemodynamic collapse and life-threatening hemodynamic collapse.

Adsorption Studies of Pb&amp;lt;sup&amp;gt;2+&amp;lt;/sup&amp;gt;, Cu&amp;lt;sup&amp;gt;2+&amp;lt;/sup&amp;gt; and Cr&amp;lt;sup&amp;gt;3+&amp;lt;/sup&amp;gt; from Aqueous Solution Using &amp;lt;i&amp;gt;Azadirachta Indica &amp;lt;/i&amp;gt;(Neem) Seed Husk and &amp;lt;i&amp;gt;Adansonia Digitata &amp;lt;/i&amp;gt;(Baobab) Seeds

The adsorption of Pb&amp;lt;sup&amp;gt;2+&amp;lt;/sup&amp;gt;, Cu&amp;lt;sup&amp;gt;2+&amp;lt;/sup&amp;gt; and Cr&amp;lt;sup&amp;gt;3+&amp;lt;/sup&amp;gt; from aqueous solution using Neem seed husk (NSH) and baobab seed (BS) were studied through the use of batch adsorption system. The adsorbents were prepared by drying at 120°C for 24hours and were characterized using FT-IR, XRD, and SEM analysis. The FTIR spectroscopy revealed the presence of O-H, N-H, C-H, C=C, C=O, and C-O stretching; XRD revealed the particle sizes as 44.51nm for NSH and 42.61nm while the morphology of the NSH and BS were revealed by SEM to be porous for NSH and BS. Various parameters such as, initial metal ion concentration, adsorbent dosage, contact time, Temperature and pH of metal ion solution were investigated in a batch-adsorption System. The adsorption uptake was found to increase with increase in adsorbent dose, contact time and temperature but decreases with the initial concentration. The uptake of the metal ions increases and reaches optimum at pH of 4-6. The maximum adsorption capacity was found to be Pb-NSH (15.267mg/g) and Cu-NSH (19.46mg/g). Adsorption of Cu&amp;lt;sup&amp;gt;2+&amp;lt;/sup&amp;gt;onto NSH fitted Langmuir isotherm model with (R&amp;lt;sup&amp;gt;2&amp;lt;/sup&amp;gt; &amp;gt; 0.93) while Adsorption of Pb-NSH Fitted Freundlich isotherm Model with (R&amp;lt;sup&amp;gt;2&amp;lt;/sup&amp;gt;&amp;gt; 0.99). Kinetic data fitted pseudo-second-order model (R&amp;lt;sup&amp;gt;2&amp;lt;/sup&amp;gt; &amp;gt; 0.98) which was more suitable in explaining the adsorption rate. Thermodynamic data showed that Gibb’s free energy (ΔG°) values for all metal ions were negative indicating feasibility and favorability of adsorption. Positive enthalpy change (ΔH°) and Entropy change (ΔS°) values indicate endothermic processes and increase in randomness.

Analyzing the Impact of Annealed Steel Sludge Doses on the Physicochemical Properties of Biochar Obtained from Waste Date Palm Frond

Large quantities of date palm frond waste generated from the pruning process are accumulated or burned in burn barrels, harming the environment and having very little economic value. However, because of the lack of data revealing the characteristic magnetic properties of biochar derived from date palm fronds, further research on low-cost and sustainable strategies could offer a new composite material and serve to extend the way for novel applications. In this study, we prepared biochar derived from palm fronds via pyrolysis under a limited-oxygen atmosphere at a lower temperature of 300 °C for 2 h. We introduced a facile strategy for the production of magnetic biochar with various doses of annealed steel sludge material via ball milling. Various amounts of annealed steel sludge material (5%, 15%, and 25% w) were added to date palm frond biochar, and the obtained product was fabricated by ball milling. The physicochemical characteristics of the magnetic biochar composite were subsequently analyzed using scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR) spectroscopy, and UV-vis spectroscopy. Our findings showed that the ball milling method is a successful step for producing date palm fronds with magnetic biochar material possessing rough and packed pores, as shown by SEM. XRD patterns assumed the existence of magnetic phases of iron oxide (magnetite (Fe3O4), hematite (α-Fe2O3), and maghemite (γ-Fe2O3) at different generated peaks. FTIR outputs exhibited the abundant presence of various oxygen-containing functional groups (- COOH and -OH) on the surface of magnetic biochar material, which help to create chemically reactive sites to adsorb potential surrounding species. The UV spectra showed a noticeable enhancement of the optical properties of the magnetic biochar with an increase in the sludge dose for light absorption in the visible region from wavelengths of 400 – 700 nm . This result signifies the synthetic optimization and potential application of magnetic biochar materials for composites that could be employed in targeted uses including soil amendment, water remediation and energy applications.

Efficacy and safety of tegoprazan- and rabeprazole-based concomitant therapies for Helicobacter pylori infection: Real-world evidence.

Tegoprazan, a novel potassium-competitive acid blocker, has been approved for Helicobacter pylori eradication in Korea. We compared the efficacy and safety of tegoprazan- and rabeprazole-based concomitant therapies for H.pylori eradication in real-world clinical practice. We retrospectively analyzed data from patients with H.pylori infection treated with tegoprazan- or rabeprazole-based concomitant therapies. The primary endpoint was H.pylori eradication rate. The secondary endpoint was adverse events. Among the 1474 included patients, 620 and 854 received tegoprazan- and rabeprazole-based concomitant therapies, respectively. Intention-to-treat analysis showed no significant difference in the eradication rates between the tegoprazan- and rabeprazole-based concomitant therapy groups (74.7% [95% confidence interval [CI], 71.1-78.0%] vs 72.7% [95% CI, 69.7-75.6%], P=0.400). Per-protocol analysis also demonstrated similar eradication rates for the groups (tegoprazan vs rabeprazole: 88.0% [95% CI, 85.0-90.6%] vs 85.9% [95% CI, 83.2-88.3%], P=0.288). Although the overall adverse event rate did not differ between groups (tegoprazan vs rabeprazole, 39.2% vs 40.6%, P=0.578), abdominal discomfort was less frequent in the tegoprazan group than in the rabeprazole group (1.3 vs 4.8%, P=0.001). Tegoprazan- and rabeprazole-based concomitant therapies for H.pylori eradication showed comparable efficacy and overall safety. The effect of tegoprazan on dose increases or other regimens, such as bismuth-containing quadruple therapy, should be further evaluated, because the efficacy of tegoprazan-based concomitant therapy may be suboptimal in regions where the clarithromycin resistance rate is high.

Recommended doses of endovenous vancomycin are insufficient to achieve therapeutic concentrations in paediatric patients

ObjectivesVancomycin therapeutic drug monitoring is challenging, especially in the paediatric population where evidence is scarce. The main objective of this study was to analyse the achievement of therapeutic concentrations of...

Treatment Targets Should Influence Choice of Infliximab Dose Intensification Strategy in Inflammatory Bowel Disease: A Pharmacokinetic Simulation Study.

The optimal infliximabdose intensification strategy to address loss of response associated with subtherapeutic infliximabtrough levels remains uncertain, as does whether post-intensification trough and treatment targets should influence this decision. This pharmacokineticsimulation study aimed to identify infliximab dose intensification strategies capable of achieving post-intensification infliximab trough thresholds associated with clinical and objective treatment targets in Crohn's disease and ulcerative colitis. A validated pharmacokinetic infliximab model, applied to 200 simulated patients, identified those with subtherapeutic (<3.00mg/L) trough levels after 30weeks of standard (5mg/kg 8-weekly) dosing, and subsequently applied 10 dose intensification strategies over a further 32weeks. The proportion of simulations achieving 32-week post-intensification infliximab trough levels associated with endoscopic remission (ulcerative colitis >7.50 mg/L, Crohn's disease >9.70 mg/L) was the primary outcome, with perianal fistula healing (Crohn's disease >10.10 mg/L) and clinical improvement (ulcerative colitis >3.70 mg/L, Crohn's disease >7.00mg/L) evaluated as secondary outcomes. All outcomes were stratified by intensity of dose intensification, with standard (≤10mg/kg 8-weekly or 5mg/kg 4-weekly; n=5) and intensive (>10mg/kg 8-weekly or 5mg/kg 4-weekly; n=5) dosing strategies defined, respectively. The median pre-intensification infliximab trough level was 0.91mg/L (interquartile range 1.37). Intensive dosing strategies were more likely to achieve infliximab trough concentrations associated with endoscopic remission (ulcerative colitis 36.48% vs. 10.80%, Crohn's disease 25.98 vs. 4.68%), perianal fistula healing (24.52% vs. 4.36%) and clinical improvement (ulcerative colitis 61.90% vs. 34.86%, Crohn's disease 40.32 vs. 12.08%) than standard intensification strategies (all p<0.01). When controlling for cumulative (mg/kg) infliximab dose over 32weeks, strategies that concurrently dose increased and interval shortened achieved the highestinfliximab trough levels (all p<0.01). This simulation-based analysis highlights the potential of using post-intensification infliximab trough thresholds associated with aspirational treatment targets in Crohn's disease and ulcerative colitis to guide choice of infliximab dose intensification strategy. Intensive dose intensification strategies, particularly those that concurrently dose increase and interval shorten, appear to achieve higher infliximab levels than standard dose intensification strategies. This may be particularly important in the pursuit of stringent endpoints, such as endoscopic remission and fistula healing, which have been consistently associated with higher infliximab trough levels. These findings require validation across real-world cohorts.

Assessment of the hormesis effect and toxic damage of short-term low-dose aflatoxin B1 in grass carp (Ctenopharyngodon idellus)

The present study was conducted to evaluate the hormesis and toxicity of short-term low-dose aflatoxin B1 in grass carp (Ctenopharyngodon idellus). Triplicate isonitrogenous and isocaloric aflatoxin B1 diets—CD (control, 0 ug/kg), D1 (20 ug/kg), and D2 (500 ug/kg)—were prepared and fed to grass carp with an initial mean body weight of (15.2 ± 0.1) g for 56 days. The results showed that the weight gain rate and specific growth rate of grass carp fed diet D2 were significantly higher, and the feed coefficient and crude fat content of the whole body were significantly lower (P &amp;lt; 0.05) compared with those fed diet CD. Serum superoxide dismutase content of grass carp fed D1 diet increased significantly (P &amp;lt; 0.05) with an increasing dose of aflatoxin B1, but when the dose reached 500 ug/kg (D2), serum superoxide dismutase, complement C3, and immunoglobulin M of grass carp decreased significantly (P &amp;lt; 0.05), while malondialdehyde increased significantly (P &amp;lt; 0.05). After short-term feeding of aflatoxin B1-containing diets (D1 and D2), liver body index, visceral body index, serum total cholesterol, triglyceride, and urea nitrogen content of grass carp increased significantly (P &amp;lt; 0.05), total bile acid secretion decreased significantly (P &amp;lt; 0.05), and structural damages such as increase in vacuoles, organizational structure loosening, and nucleus translocation were observed in the liver. Meanwhile, liver function indexes such as serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase increased significantly with the increase of aflatoxin B1 dose (P &amp;lt; 0.05). In addition, the height of intestinal villi, crypt depth, villus–crypt ratio, and tubular cell number, as well as the content of trypsin and lipase activities in the intestine of grass carp in the D2 group, were significantly higher than those in the CD group (P &amp;lt; 0.05). In conclusion, after a short-term intake of low doses of aflatoxin B1 (≤500 ug/kg), the toxicological damage of aflatoxin B1 was pronounced, although it produced a certain degree of hormesis on the growth performance and intestinal structure and function of grass carp. At a dose of 20 ug/kg, the non-specific immune system and liver structure and function of grass carp showed obvious toxic damage.

Hypogammaglobulinemia and Infection Events in Patients with Autoimmune Diseases Treated with Rituximab: 10 Years Real-Life Experience.

To investigate predictors of hypogammaglobulinemia (HGG) and severe infection event (SIE) in patients with autoimmune disease (AID) receiving rituximab (RTX) therapy. This was a retrospective study conducted in a tertiary medical center in China. Predictors of HGG or SIE were assessed using Cox analysis. Restricted cubic spline (RCS) analysis was applied to examine the correlation between glucocorticoid (GC) maintenance dose and SIE. A total of 219 patients were included in this study, with a cumulative follow-up time of 698.28 person-years. Within the study population, 117 patients were diagnosed with connective tissue disease, 75 patients presented with ANCA-associated vasculitis, and 27 patients exhibited IgG4-related disease. HGG was reported in 63.3% of the patients, where an obvious decline in IgG and IgM was shown three months after RTX initiation. The rate of SIE was 7.2 per 100 person-years. An increase in the GC maintenance dose was an independent risk factor for both hypo-IgG (HR 1.07, 95% CI 1.02-1.12, p = 0.003) and SIE (HR 1.06, 95% CI 1.02-1.1, p = 0.004). Further RCS analysis identified 7.48mg/d prednisone as a safe threshold dose for patients who underwent RTX treatment to avoid a significantly increased risk for SIE. HGG was relatively common in RTX-treated AID patients. Patients with chronic lung disease or who were taking ≥ 7.5mg/d prednisone during RTX treatment were at increased risk for SIE and warrant attention from physicians.