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AAPS PharmSciTech Jun 2024The current treatment for oral inflammatory ulcerative diseases has limitations. In situ forming hydrogels have shown great potential to deliver therapeutic substances...
The current treatment for oral inflammatory ulcerative diseases has limitations. In situ forming hydrogels have shown great potential to deliver therapeutic substances for drug delivery to the buccal cavity. This study aimed to prepare and characterize lipid- and surfactant-based mixed micelle in situ gel (MIG) and evaluate whether it can offer more favorable properties than the in situ gel for effective treatment of the disease. Dexamethasone was incorporated into the MIGs particles, based on Poloxamer 407 and chitosan. The lower gelation time at 37 ℃ was considered a criterion to select superior formulations among the different lipid- and surfactant-based candidates. Further characterization was performed to evaluate the opted formulations regarding morphology, physical stability, rheology, texture, and release profile. All formulations were thermoresponsive and had a shorter gelation time as the temperature increased. Dexamethasone was released in a highly controlled manner, and morphological evaluation revealed that the mixed micelle in situ gels had spherical nanoparticles. Thixotropic behavior was observed in all MIGs, indicating a prolonged retention time of the formulation after oral administration. This study has shown that among different MIGs, the one with oleic acid is a more promising candidate than the in situ gel and other MIGs for drug delivery to the buccal cavity.
Topics: Micelles; Dexamethasone; Chitosan; Gels; Drug Delivery Systems; Poloxamer; Drug Liberation; Surface-Active Agents; Chemistry, Pharmaceutical; Hydrogels; Anti-Inflammatory Agents; Nanoparticles; Drug Carriers; Rheology; Oral Ulcer; Administration, Oral; Lipids; Oleic Acid
PubMed: 38918282
DOI: 10.1208/s12249-024-02862-2 -
PloS One 2024The aim of this study was to evaluate the impact of intravenous palonosetron compared to ondansetron on hypotension induced by spinal anesthesia in women undergoing... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The aim of this study was to evaluate the impact of intravenous palonosetron compared to ondansetron on hypotension induced by spinal anesthesia in women undergoing cesarean section.
METHODS
Fifty-four women scheduled for elective cesarean section were, randomly allocated to ondansetron group (n = 27) or palonosetron group (n = 27). Ten minutes prior to the administration of spinal anesthesia, participants received an intravenous injection of either ondansetron or palonosetron. A prophylactic phenylephrine infusion was initiated immediately following the intrathecal administration of bupivacaine and fentanyl. The infusion rate was titrated to maintain adequate blood pressure until the time of fetal delivery. The primary outcome was total dose of phenylephrine administered. The secondary outcomes were nausea or vomiting, the need for rescue antiemetics, hypotension, bradycardia, and shivering. Complete response rate, defined as the absence of postoperative nausea and vomiting and no need for additional antiemetics, were assessed for up to 24 hours post-surgery.
RESULTS
No significant differences were observed in the total dose of phenylephrine used between the ondansetron and palonosetron groups (387.5 μg [interquartile range, 291.3-507.8 μg versus 428.0 μg [interquartile range, 305.0-507.0 μg], P = 0.42). Complete response rates also showed no significant differences between the groups both within two hours post-spinal anesthesia (88.9% in the ondansetron group versus 100% in the palonosetron group; P = 0.24) and at 24 hours post-surgery (81.5% in the ondansetron group versus 88.8% in the palonosetron group; P = 0.7). In addition, there was no difference in other secondary outcomes.
CONCLUSION
Prophylactic administration of palonosetron did not demonstrate a superior effect over ondansetron in mitigating hemodynamic changes or reducing phenylephrine requirements in patients undergoing spinal anesthesia with bupivacaine and fentanyl for cesarean section.
Topics: Humans; Female; Anesthesia, Spinal; Cesarean Section; Palonosetron; Adult; Hypotension; Pregnancy; Ondansetron; Antiemetics; Postoperative Nausea and Vomiting; Phenylephrine; Anesthesia, Obstetrical
PubMed: 38917195
DOI: 10.1371/journal.pone.0305913 -
Journal of Hematology & Oncology Jun 2024It remains a substantial challenge to balance treatment efficacy and toxicity in geriatric patients with multiple myeloma (MM), primarily due to the dynamic nature of...
It remains a substantial challenge to balance treatment efficacy and toxicity in geriatric patients with multiple myeloma (MM), primarily due to the dynamic nature of frailty. Here, we conducted a prospective study to evaluate the feasibility and benefits of dynamic frailty-tailored therapy (DynaFiT) in elderly patients. Patients with newly diagnosed MM (aged ≥ 65 years) received eight induction cycles of bortezomib, lenalidomide, and dexamethasone (daratumumab was recommended for frail patients), with treatment intensity adjusted according to longitudinal changes in the frailty category (IMWG-FI) at each cycle. Of 90 patients, 33 (37%), 16 (18%), and 41 (45%) were fit, intermediate fit, and frail at baseline, respectively. Of 75 patients who had geriatric assessment at least twice, 28 (37%) experienced frailty category changes at least once. At analysis, 15/26 (58%) frail patients improved (27% became fit and 31% became intermediate fit), 4/15 (27%) intermediate fit patients either improved or deteriorated (two for each), and 6/30 (20%) fit patients deteriorated. During induction, 34/90 (38%) patients discontinued treatment, including 10/33 (30%) fit, 4/16 (25%) intermediate fit, and 20/41 (49%) frail; 14/40 (35%) frail patients discontinued treatment within the first two cycles, mainly because of non-hematologic toxicity (mostly infections). For fit, intermediate-fit, and frail patients, the overall response rate was 100%, 93%, and 73%, respectively; one-year overall survival was 90%, 75%, and 54%, respectively. Therefore, the individualized DynaFiT is feasible and promising for heterogeneous elderly patients.
Topics: Humans; Multiple Myeloma; Aged; Prospective Studies; Male; Female; Aged, 80 and over; Dexamethasone; Antineoplastic Combined Chemotherapy Protocols; Frailty; Lenalidomide; Bortezomib; Precision Medicine; Frail Elderly; Geriatric Assessment; Antibodies, Monoclonal
PubMed: 38915117
DOI: 10.1186/s13045-024-01569-y -
ELife Jun 2024The serotonin-gated ion channel (5-HTR) mediates excitatory neuronal communication in the gut and the brain. It is the target for setrons, a class of competitive...
The serotonin-gated ion channel (5-HTR) mediates excitatory neuronal communication in the gut and the brain. It is the target for setrons, a class of competitive antagonists widely used as antiemetics, and is involved in several neurological diseases. Cryo-electron microscopy (cryo-EM) of the 5-HTR in complex with serotonin or setrons revealed that the protein has access to a wide conformational landscape. However, assigning known high-resolution structures to actual states contributing to the physiological response remains a challenge. In the present study, we used voltage-clamp fluorometry (VCF) to measure simultaneously, for 5-HTR expressed at a cell membrane, conformational changes by fluorescence and channel opening by electrophysiology. Four positions identified by mutational screening report motions around and outside the serotonin-binding site through incorporation of cysteine-tethered rhodamine dyes with or without a nearby quenching tryptophan. VCF recordings show that the 5-HTR has access to four families of conformations endowed with distinct fluorescence signatures: 'resting-like' without ligand, 'inhibited-like' with setrons, 'pre-active-like' with partial agonists, and 'active-like' (open channel) with partial and strong agonists. Data are remarkably consistent with cryo-EM structures, the fluorescence partners matching respectively apo, setron-bound, 5-HT bound-closed, and 5-HT-bound-open conformations. Data show that strong agonists promote a concerted motion of all fluorescently labeled sensors during activation, while partial agonists, especially when loss-of-function mutations are engineered, stabilize both active and pre-active conformations. In conclusion, VCF, though the monitoring of electrophysiologically silent conformational changes, illuminates allosteric mechanisms contributing to signal transduction and their differential regulation by important classes of physiological and clinical effectors.
Topics: Receptors, Serotonin, 5-HT3; Fluorometry; Humans; Patch-Clamp Techniques; Protein Conformation; Serotonin; Cryoelectron Microscopy; HEK293 Cells; Binding Sites; Ion Channel Gating
PubMed: 38913422
DOI: 10.7554/eLife.93174 -
International Ophthalmology Jun 2024Macular edema (ME) is a common complication following branch retinal vein occlusion (BRVO) and is also the main reason for visual impairment. This study aimed to compare... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
BACKGROUND
Macular edema (ME) is a common complication following branch retinal vein occlusion (BRVO) and is also the main reason for visual impairment. This study aimed to compare the efficacy and safety of intravitreal ranibizumab (IVR) or dexamethasone implant (IDI) monotherapy, as well as the combination of IVR and IDI injections, in patients with ME secondary to branch retinal vein occlusion (BRVO).
METHODS
This multicenter, prospective, and comparative study included 292 patients with unilateral ME involvement (total of 292 eyes) secondary to BRVO. The patients were randomly assigned to three groups and followed up for 12 months. Patients in group 1 (n = 96) were treated with 3-dose loading IVR injections followed by a pro re nata (PRN) regimen. Patients in group 2 (n = 98) received IVR combined with IDI injection, followed by IVR PRN regimen. Patients in group 3 (n = 98) were treated with IDI injection, followed by repeated IDI injection based on clinical necessity. Best corrected visual acuity (BCVA), central retinal thickness (CRT), complications, and frequency of injections were recorded and compared between the three groups.
RESULTS
At baseline, the three groups did not differ in age, gender, duration of ME, BCVA, IOP, and CRT (P > 0.05). Mean number of total injections per eye within 12 months were 7.1 ± 2.3 (range 4-9) in group 1, 3.7 ± 1.5 (range 2-6) in group 2, and 1.8 ± 0.4 (range 1-3) in group 3. There was a statistical difference in the number of injections between group 1 and group 2 (P = 0.037). Eyes in group 3 received fewer injections than those in group 2, but the difference was not statistically significant (P = 0.052). BCVA improvement and CRT reduction were achieved in all groups and there was no significant difference between the three groups at the end of the 12th month. However, IOP elevation and cataract progression were more frequent in group 3, especially in those patients who received repeated IDI injections.
CONCLUSION
Three therapeutic regimens had comparable efficacy in treating ME secondary to BRVO. Combination therapy had an advantage in maintaining good effect with fewer re-injections and complications.
TRIAL REGISTRATION INFORMATION
The study complied with the principles of the Declaration of Helsinki and was approved by Xi'an Aier Ancient City Eye Hospital, Xi'an Aier Eye Hospital, and Xianyang Aier Eye Hospital ethics committees (2022SF-367).
Topics: Humans; Retinal Vein Occlusion; Ranibizumab; Male; Female; Dexamethasone; Intravitreal Injections; Macular Edema; Prospective Studies; Drug Implants; Visual Acuity; Middle Aged; Angiogenesis Inhibitors; Glucocorticoids; Tomography, Optical Coherence; Treatment Outcome; Aged; Drug Therapy, Combination; Follow-Up Studies
PubMed: 38913192
DOI: 10.1007/s10792-024-03158-x -
Supportive Care in Cancer : Official... Jun 2024This study describes chemotherapy-induced nausea and vomiting (CINV) control rates in pediatric and adult patients who did or did not receive guideline-consistent CINV... (Review)
Review
PURPOSE
This study describes chemotherapy-induced nausea and vomiting (CINV) control rates in pediatric and adult patients who did or did not receive guideline-consistent CINV prophylaxis.
METHODS
We conducted a systematic literature review of studies published in 2000 or later that evaluated CINV control in patients receiving guideline-consistent vs. guideline-inconsistent CINV prophylaxis and reported at least one CINV-related patient outcome. Studies were excluded if the guideline evaluated was not publicly available or not developed by a professional organization. Over-prophylaxis was defined as antiemetic use recommended for a higher level of chemotherapy emetogenicity than a patient was receiving.
RESULTS
We identified 7060 citations and retrieved 141 publications for full-text evaluation. Of these, 21 publications (14 prospective and seven retrospective studies) evaluating guidelines developed by six organizations were included. The terms used to describe CINV endpoints and definition of guideline-consistent CINV prophylaxis varied among studies. Included studies either did not address over-prophylaxis in their definition of guideline-consistent CINV prophylaxis (48%; 10/21) or defined it as guideline-inconsistent (38%; 8/21) or guideline-consistent (3/21; 14%). Eleven included studies (52%; 11/21) reported a clinically meaningful improvement in at least one CINV endpoint in patients receiving guideline-consistent CINV prophylaxis. Ten reported a statistically significant improvement.
CONCLUSIONS
This evidence supports the use of guideline-consistent prophylaxis to optimize CINV control. Institutions caring for patients with cancer should systematically adapt CINV CPGs for local implementation and routinely evaluate CINV outcomes.
Topics: Humans; Nausea; Vomiting; Antineoplastic Agents; Adult; Antiemetics; Child; Neoplasms; Guideline Adherence; Practice Guidelines as Topic; Treatment Outcome
PubMed: 38913170
DOI: 10.1007/s00520-024-08623-y -
Journal of Maxillofacial and Oral... Jun 2024The aim of this study was to compare the efficacy and safety of transdermal Fentanyl patch with oral Ketorolac for pain management in dry socket patients.
OBJECTIVES
The aim of this study was to compare the efficacy and safety of transdermal Fentanyl patch with oral Ketorolac for pain management in dry socket patients.
STUDY DESIGN
Sixty patients who were diagnosed with dry socket (VAS > 40 mm) were recruited in this prospective randomized controlled trial. Patients were divided into two groups. Group1 ( = 30) Transdermal Fentanyl patch (25mcg/hr) was given and in Group 2 ( = 30) Ketorolac 10 mg Oral tablet was prescribed for pain management. The primary endpoint was the mean pain scores within 72 h evaluated by visual analog scale (VAS). Secondary measures included the safety and tolerability, amount of rescue medication (analgesic and antiemetic) and effectiveness of treatment interventions by Brief Pain Inventory Questionnaire (BPI).
RESULTS
The mean VAS pain scores were significantly less in group 1 (Fentanyl) as compared to group 2 (ketorolac) on all follow-up days. Significant difference was noted in the mean amount of rescue analgesic medication. It was 2.16 + 1.53 in group 1 and 8.50 + 3.98 in group 2. Side effects were seen in both the groups. Nausea (46%) and vomiting (43%) were reported in group 1 while headache (36.6%) and epigastric pain (53.3%) in group 2.
CONCLUSIONS
Thus, transdermal Fentanyl was better in pain control than Ketorolac with less need for rescue analgesic medication in dry socket.
PubMed: 38911417
DOI: 10.1007/s12663-022-01713-6 -
Drug Design, Development and Therapy 2024
Randomized Controlled Trial
Penehyclidine for Prevention of Postoperative Nausea and Vomiting in Patients Undergoing Gynecological Laparoscopic Surgery Under Combined Intravenous and Inhalation Anesthesia: A Randomized, Double-Blind, Placebo-Controlled Trial [Letter].
Topics: Humans; Double-Blind Method; Laparoscopy; Female; Quinuclidines; Postoperative Nausea and Vomiting; Gynecologic Surgical Procedures; Anesthesia, Inhalation; Antiemetics; Randomized Controlled Trials as Topic; Anesthesia, Intravenous
PubMed: 38911028
DOI: 10.2147/DDDT.S482220 -
BMJ Open Jun 2024Although the prognosis of Langerhans cell histiocytosis (LCH) is excellent, the high recurrence rate and permanent consequences, such as central diabetes insipidus and...
INTRODUCTION
Although the prognosis of Langerhans cell histiocytosis (LCH) is excellent, the high recurrence rate and permanent consequences, such as central diabetes insipidus and LCH-associated neurodegenerative diseases, remain to be resolved. Based on previous reports that patients with high-risk multisystem LCH show elevated levels of inflammatory molecules, we hypothesised that dexamethasone would more effectively suppress LCH-associated inflammation, especially in the central nervous system (CNS). We further hypothesised that intrathecal chemotherapy would effectively reduce CNS complications. We administer zoledronate to patients with multifocal bone LCH based on an efficacy report from a small case series.
METHODS AND ANALYSIS
This phase II study (labelled the LCH-19-MSMFB study) is designed to evaluate the significance of introducing dexamethasone and intrathecal chemotherapy for multisystem disease and zoledronate for multifocal bone disease in previously untreated, newly diagnosed children, adolescents (under 20 years) and adults under 40 years. The primary endpoint is the 3-year event-free survival rate by risk group of under 20 years and the 3-year event-free survival rate of 20 years and over.
ETHICS AND DISSEMINATION
This study was approved by the Central Review Board of the National Hospital Organisation Nagoya Medical Centre (Nagoya, Japan) on 21 January 2022 and was registered in the Japan Registry of Clinical Trials (https://jrct.niph.go.jp/en-latest-detail/jRCTs041210027). Written informed consent will be obtained from all patients and/or their guardians.
TRIAL REGISTRATION NUMBER
jRCTs041210027.
Topics: Humans; Histiocytosis, Langerhans-Cell; Child; Adolescent; Japan; Adult; Dexamethasone; Young Adult; Zoledronic Acid; Male; Female; Clinical Trials, Phase II as Topic; Child, Preschool; Bone Density Conservation Agents
PubMed: 38910000
DOI: 10.1136/bmjopen-2024-084159 -
Scientific Reports Jun 2024Head-fixation of mice enables high-resolution monitoring of neuronal activity coupled with precise control of environmental stimuli. Virtual reality can be used to...
Head-fixation of mice enables high-resolution monitoring of neuronal activity coupled with precise control of environmental stimuli. Virtual reality can be used to emulate the visual experience of movement during head fixation, but a low inertia floating real-world environment (mobile homecage, MHC) has the potential to engage more sensory modalities and provide a richer experimental environment for complex behavioral tasks. However, it is not known whether mice react to this adapted environment in a similar manner to real environments, or whether the MHC can be used to implement validated, maze-based behavioral tasks. Here, we show that hippocampal place cell representations are intact in the MHC and that the system allows relatively long (20 min) whole-cell patch clamp recordings from dorsal CA1 pyramidal neurons, revealing sub-threshold membrane potential dynamics. Furthermore, mice learn the location of a liquid reward within an adapted T-maze guided by 2-dimensional spatial navigation cues and relearn the location when spatial contingencies are reversed. Bilateral infusions of scopolamine show that this learning is hippocampus-dependent and requires intact cholinergic signalling. Therefore, we characterize the MHC system as an experimental tool to study sub-threshold membrane potential dynamics that underpin complex navigation behaviors.
Topics: Animals; Mice; Spatial Navigation; Maze Learning; Male; Hippocampus; Pyramidal Cells; Mice, Inbred C57BL; Membrane Potentials; CA1 Region, Hippocampal; Virtual Reality; Scopolamine; Patch-Clamp Techniques
PubMed: 38906952
DOI: 10.1038/s41598-024-64807-w