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World Journal of Gastroenterology Jun 2024The combination of endoscopic ultrasound with endoscopic treatment of type 1 gastric variceal hemorrhage may improve the robustness and generalizability of the findings...
The combination of endoscopic ultrasound with endoscopic treatment of type 1 gastric variceal hemorrhage may improve the robustness and generalizability of the findings in future studies. Moreover, the esophageal varices should also be included in the evaluation of treatment efficacy in subsequent studies to reach a more convincing conclusion.
Topics: Esophageal and Gastric Varices; Humans; Ligation; Treatment Outcome; Gastrointestinal Hemorrhage; Tissue Adhesives; Endosonography; Injections; Hemostasis, Endoscopic; Endoscopy, Gastrointestinal
PubMed: 38899333
DOI: 10.3748/wjg.v30.i21.2827 -
Ciencia & Saude Coletiva Jun 2024This article aims to discuss the expectations of Homosexual Men, Bisexual Men and a Transgender Woman, who use or want to use an oral pre-exposure prophylaxis (PrEP) for...
This article aims to discuss the expectations of Homosexual Men, Bisexual Men and a Transgender Woman, who use or want to use an oral pre-exposure prophylaxis (PrEP) for the human immunodeficiency virus (HIV) about PrEP modalities. Sixteen PrEP users, who are followed up in the BCN Checkpoint, were interviewed,. The interviews were audio-recorded, subjected to thematic categorical analysis within the theoretical framework from the praxiographic perspective. They are all adapted to the use of daily oral and event-based PrEP. In relation to the new PrEP modalities (monthly pill; intramuscular injection every two months; subcutaneous injection every six months), they are all very receptive to these possibilities, but they lack information on the specificities of each and specific assessment of their needs. Comments about the use of oral PrEP are positive, and expectations regarding the new PrEP modalities are visibly high. However, the most important thing for the interviewees is the guarantee that they will have follow-up appointments to continue taking care of their affective-sexual health, which is not dependent on the type of PrEP modalities.
Topics: Humans; Pre-Exposure Prophylaxis; Male; HIV Infections; Female; Adult; Anti-HIV Agents; Sexual and Gender Minorities; Interviews as Topic; Transgender Persons; Administration, Oral; Middle Aged; Young Adult; Injections, Intramuscular
PubMed: 38896667
DOI: 10.1590/1413-81232024296.03042023 -
Journal of Clinical Immunology Jun 2024Facilitated subcutaneous immunoglobulin (fSCIG; immune globulin infusion 10% [human] with recombinant human hyaluronidase [rHuPH20]) permits high-volume subcutaneous...
Tolerability and Safety of Large-Volume Hyaluronidase-Facilitated Subcutaneous Immunoglobulin 10% Administered with or without Dose Ramp-Up: A Phase 1 Study in Healthy Participants.
PURPOSE
Facilitated subcutaneous immunoglobulin (fSCIG; immune globulin infusion 10% [human] with recombinant human hyaluronidase [rHuPH20]) permits high-volume subcutaneous immunoglobulin (SCIG) infusion, shorter infusion times and reduced dosing frequency relative to conventional SCIG. It is initiated by gradually increasing infusion volumes over time (dose ramp-up) to achieve target dose level (TDL). Whether ramp-up strategies have tolerability or safety advantages over direct initiation at full TDL has not been evaluated clinically.
METHODS
This phase 1 open-label study assessed tolerability and safety of fSCIG 10% with accelerated or no ramp-up compared with conventional ramp-up in healthy adults (NCT04578535). Participants were assigned to one of the three ramp-up arms to achieve TDLs of 0.4 or 1.0 g/kg/infusion. The primary endpoint was the proportion of infusions completed without interruption or infusion rate reduction owing to treatment-emergent adverse events (TEAEs). Safety was assessed as a secondary endpoint.
RESULTS
Of 51 participants enrolled, 50 (98.0%) tolerated all fSCIG 10% infusions initiated (n = 174). Infusion rate was reduced in one participant owing to headache in the 0.4 g/kg/infusion conventional ramp-up arm. Study discontinuations were higher in the no ramp-up arm (70%) versus the conventional (0%) and accelerated (22%) arms at the 1.0 g/kg/infusion TDL. Safety outcomes did not substantially differ between treatment arms.
CONCLUSION
The favorable tolerability and safety profiles of fSCIG 10% in healthy participants support initiating treatment with fSCIG 10% with accelerated ramp-up at TDLs up to 1.0 g/kg. Data support no ramp-up at TDLs close to 0.4 g/kg but additional data are needed for higher doses.
Topics: Humans; Hyaluronoglucosaminidase; Male; Female; Adult; Healthy Volunteers; Infusions, Subcutaneous; Young Adult; Middle Aged; Immunoglobulins; Recombinant Proteins; Adolescent
PubMed: 38896141
DOI: 10.1007/s10875-024-01742-5 -
Lakartidningen Jun 2024
Topics: Humans; Anti-Bacterial Agents; beta-Lactams; Infusions, Intravenous; Practice Guidelines as Topic; beta Lactam Antibiotics
PubMed: 38895758
DOI: No ID Found -
Drug Design, Development and Therapy 2024This study compared the pharmacokinetics, safety and bioequivalence (BE) of generic and original apremilast tablets in healthy Chinese subjects under fasting and... (Randomized Controlled Trial)
Randomized Controlled Trial Clinical Trial
OBJECTIVE
This study compared the pharmacokinetics, safety and bioequivalence (BE) of generic and original apremilast tablets in healthy Chinese subjects under fasting and postprandial conditions, providing sufficient evidence for abbreviated new drug application.
METHODS
A randomized, open-label, two-formulation, single-dose, two-period crossover pharmacokinetic study was performed. Thirty-two eligible healthy Chinese subjects were enrolled in fasting and postprandial studies, respectively. In each trial, subjects received a single 30-mg dose of the test or reference apremilast tablet, followed by a 7-day washout interval between periods. Serial blood samples were obtained for up to 48 h post-intake in each period, and the plasma concentrations of apremilast were determined by a validated method. The primary pharmacokinetic (PK) parameters, including the maximum plasma concentration (C), the areas under the plasma concentration-time curve (AUC, AUC), were calculated using the non-compartmental method. The geometric mean ratios of the two formulations and the corresponding 90% confidence intervals (CIs) were acquired for bioequivalence analysis. The safety of both formulations was also evaluated.
RESULTS
Under fasting and postprandial states, the PK parameters of the test drug were similar to those of the reference drug. The 90% CIs of the geometric mean ratios of the test to reference formulations were 94.09-103.44% for C, 94.05-103.51% for AUC, and 94.56-103.86% for AUC under fasting conditions, and 99.18-112.48% for C, 98.79-106.02% for AUC, and 98.95-105.89% for AUC under postprandial conditions, all of which were within the bioequivalence range of 80.00-125.00%. Both formulations were well tolerated, and no serious adverse events occurred during the study.
CONCLUSION
The trial confirmed that the PK parameters of the generic and original apremilast tablets were bioequivalent in healthy Chinese subjects under fasting and postprandial states, which met the predetermined regulatory standards. Both formulations were safe and well tolerated.
CLINICAL TRIAL REGISTRATION
chinaDrugtrials.org.cn, identifier CTR20191056 (July 30, 2019); chictr.org.cn, identifier ChiCTR2300076806 (October 19, 2023).
Topics: Humans; Therapeutic Equivalency; Thalidomide; Fasting; Postprandial Period; Adult; Male; Cross-Over Studies; Healthy Volunteers; Tablets; Young Adult; Female; Anti-Inflammatory Agents, Non-Steroidal; Asian People; Area Under Curve; Administration, Oral
PubMed: 38895175
DOI: 10.2147/DDDT.S461771 -
Molecules (Basel, Switzerland) Jun 2024Itampolin A, a natural brominated tyrosine alkaloid isolated from the sponge , has been shown to have good inhibitory effects in lung cancer cells as a p38α inhibitor....
Pharmacokinetics and Tissue Distribution of Itampolin A following Intragastric and Intravenous Administration in Rats Using Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry.
Itampolin A, a natural brominated tyrosine alkaloid isolated from the sponge , has been shown to have good inhibitory effects in lung cancer cells as a p38α inhibitor. A simple, sensitive, and reliable ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method has been established, validated, and applied to the study of the pharmacokinetics and tissue distribution of itampolin A following intragastric and intravenous administration. Itampolin A and theophylline (internal standard, IS) were extracted by the simple protein precipitation technique using methanol as the precipitating solvent. Chromatographic separation was achieved by using the optimized mobile phase of a 0.1% formic acid aqueous solution and acetonitrile in the gradient elution mode. Itampolin A and IS were detected and quantified using positive electrospray ionization in the multiple reaction monitoring mode with transitions of / 863.9 → 569.1 for itampolin A and / 181.1 → 124.1 for IS, respectively. The assay exhibited a linear dynamic range of 1-1600 ng/mL for itampolin A in biological samples and the low limit of quantification was 1 ng/mL. Non-compartmental pharmacokinetic parameters indicated that itampolin A was well-absorbed into the systemic circulation and rapidly eliminated after administration. The apparent distribution volume of itampolin A was much higher after intragastric administration than that after intravenous administration. A tissue distribution study showed that itampolin A could be detected in different tissues and maintained a high concentration in the lung, which provided a material basis for its effective application in lung cancer. The pharmacokinetic process and tissue distribution characteristics of imtapolin A were expounded in this study, which can provide beneficial information for the further research and clinical application of itampolin A.
Topics: Animals; Tandem Mass Spectrometry; Tissue Distribution; Chromatography, High Pressure Liquid; Administration, Intravenous; Rats; Male; Rats, Sprague-Dawley
PubMed: 38893526
DOI: 10.3390/molecules29112652 -
Molecules (Basel, Switzerland) Jun 2024Oral anticoagulant therapy (OAT) for managing atrial fibrillation (AF) encompasses vitamin K antagonists (VKAs, such as warfarin), which was the mainstay of...
Oral anticoagulant therapy (OAT) for managing atrial fibrillation (AF) encompasses vitamin K antagonists (VKAs, such as warfarin), which was the mainstay of anticoagulation therapy before 2010, and direct-acting oral anticoagulants (DOACs, namely dabigatran etexilate, rivaroxaban, apixaban, edoxaban), approved for the prevention of AF stroke over the last thirteen years. Due to the lower risk of major bleeding associated with DOACs, anticoagulant switching is a common practice in AF patients. Nevertheless, there are issues related to OAT switching that still need to be fully understood, especially for patients in whom AF and heart failure (HF) coexist. Herein, the effective impact of the therapeutic switching from warfarin to DOACs in HF patients with AF, in terms of cardiac remodeling, clinical status, endothelial function and inflammatory biomarkers, was assessed by a machine learning (ML) analysis of a clinical database, which ultimately shed light on the real positive and pleiotropic effects mediated by DOACs in addition to their anticoagulant activity.
Topics: Humans; Atrial Fibrillation; Heart Failure; Machine Learning; Anticoagulants; Administration, Oral; Male; Female; Aged; Chronic Disease; Warfarin
PubMed: 38893525
DOI: 10.3390/molecules29112651 -
Nutrients May 2024Palmitoylethanolamide (PEA) emerged over the years as a promising approach in the management of chronic pain. Despite the fact that the efficacy of micron-size PEA... (Meta-Analysis)
Meta-Analysis Review
Palmitoylethanolamide (PEA) emerged over the years as a promising approach in the management of chronic pain. Despite the fact that the efficacy of micron-size PEA formulations appears to be time-dependent, the optimal timing has not yet been elucidated. This systematic review and meta-analysis aim to estimate the possible advantage of an extended treatment in the relief of chronic pain. The literature search was conducted consulting scientific databases, to identify clinical trials in which micron-size PEA was administered for at least 60 days, and pain assessed by the Visual Analogue Scale (VAS) or Numeric Rating Scale (NRS). Nine studies matched the required criteria, for a total of 742 patients involved. The meta-analysis showed a statistically and clinically significant pain intensity reduction after 60 days of micron-size PEA supplementation, compared to 30 days (1.36 points, < 0.01). The secondary analysis revealed a weighted NRS/VAS score decrease of 2.08 points within the first month of treatment. These two obtained scores corresponded to a 35.1% pain intensity reduction within the first month, followed by a further 35.4% during the second month. Overall, these results confirm the clinically relevant and time-depended pain-relieving effect of micron-size PEA and therefore the advantage of an extended treatment, especially in patient with incomplete pain management.
Topics: Palmitic Acids; Humans; Amides; Ethanolamines; Chronic Pain; Pain Measurement; Administration, Oral; Treatment Outcome; Analgesics
PubMed: 38892586
DOI: 10.3390/nu16111653 -
Nutrients May 2024The aim of this pilot study was to evaluate and compare bioavailability and safety of two Vitamin D formulations (softgels) in healthy adults, at single daily doses of... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
The aim of this pilot study was to evaluate and compare bioavailability and safety of two Vitamin D formulations (softgels) in healthy adults, at single daily doses of 1000 and 2500 IU, over a 60-day period. A total of 69 participants were initially screened for eligibility in a double-blind randomized study with a four-arm parallel design; 35 participants were randomized to treatment groups: (1) standard Vitamin D 1000 IU (STD1000), (2) micellar Vitamin D 1000 IU (LMD1000), (3) standard Vitamin D 2500 IU (STD2500), and (4) micellar Vitamin D 2500 IU (LMD2500). Serum Vitamin D concentrations were determined through calcifediol [25(OH)D] at baseline (=before treatment), at day 5, 10, and 15 (=during treatment), at day 30 (=end of treatment), and at day 45 and 60 (=during follow-up/post treatment). Safety markers and minerals were evaluated at baseline and at day 30 and day 60. The pharmacokinetic parameters with respect to iAUC were found to be significantly different between LMD1000 vs. STD1000: iAUC(5-60): 992 ± 260 vs. 177 ± 140 nmol day/L; < 0.05, suggesting up to 6 times higher Vitamin D absorption of LMD when measured incrementally. During follow-up, participants in the LMD1000 treatment group showed approx. 7 times higher Vitamin D concentrations than the STD1000 group (iAUC(30-60): 680 ± 190 vs. 104 ± 91 nmol day/L; < 0.05). However, no significant differences were found between the pharmacokinetics of the higher dosing groups STD2500 and LMD2500. No significant changes in serum 1,25(OH)D concentrations or other biochemical safety markers were detected at day 60; no excess risks of hypercalcemia (i.e., total serum calcium > 2.63 mmol/L) or other adverse events were identified. LMD, a micellar delivery vehicle for microencapsulating Vitamin D (LipoMicel), proved to be safe and only showed superior bioavailability when compared to standard Vitamin D at the lower dose of 1000 IU. This study has clinical trial registration: NCT05209425.
Topics: Humans; Pilot Projects; Cholecalciferol; Male; Female; Double-Blind Method; Adult; Dietary Supplements; Micelles; Biological Availability; Administration, Oral; Middle Aged; Young Adult; Calcifediol; Vitamin D
PubMed: 38892507
DOI: 10.3390/nu16111573 -
Nutrients May 2024Skin problems caused by aging have attracted much attention, and marine collagen peptides have been proved to improve these problems, while mammalian collagen peptides...
Oral Administration of Deer Bone Collagen Peptide Can Enhance the Skin Hydration Ability and Antioxidant Ability of Aging Mice Induced by D-Gal, and Regulate the Synthesis and Degradation of Collagen.
Skin problems caused by aging have attracted much attention, and marine collagen peptides have been proved to improve these problems, while mammalian collagen peptides are rarely reported. In this study, fermented deer bone collagen peptide (FCP) and non-fermented deer bone collagen peptide (NCP) were extracted from fermented and non-fermented deer bone, respectively, and their peptide sequences and differential proteins were analyzed using LC-MS/MS technology. After they were applied to aging mice induced with D-gal, the skin hydration ability, antioxidant ability, collagen synthesis, and degradation ability of the mice were studied. The results show that FCP and NCP are mainly peptides that constitute type Ⅰ collagen, and their peptide segments are different. In vivo experiments show that FCP and NCP can improve the richness of collagen fibers in the skin of aging mice; improve the hydration ability of skin; promote the activity of antioxidant-related enzymes; and also show that through the TGF-β and MAPK pathways, the synthesis and degradation of collagen in skin are regulated. These results show that deer bone collagen peptide can improve skin problems caused by aging, promote skin hydration and antioxidant capacity of aging mice, and regulate collagen synthesis and degradation through the MAPK pathway.
Topics: Animals; Deer; Antioxidants; Mice; Skin; Bone and Bones; Collagen; Aging; Administration, Oral; Peptides; Skin Aging; Male; Fermentation; Collagen Type I
PubMed: 38892482
DOI: 10.3390/nu16111548