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Research Square Sep 2023Prediction of high-risk events in mental disorder patients is crucial. In our previous study, we developed a deep learning model: DeepBiomarker by using electronic...
Prediction of Adverse Events Risk in Patients with Comorbid Post- Traumatic Stress Disorder and Alcohol Use Disorder Using Electronic Medical Records by Deep Learning Models.
BACKGROUND
Prediction of high-risk events in mental disorder patients is crucial. In our previous study, we developed a deep learning model: DeepBiomarker by using electronic medical records (EMR) to predict suicide related event (SRE) risk in post-traumatic stress disorder (PTSD) patients.
METHODS
We applied DeepBiomarker2 through data integration of multimodal information: lab test, medication, co-morbidities, and social determinants of health. We analyzed EMRs of 5,565 patients from University of Pittsburgh Medical Center with a diagnosis of PTSD and alcohol use disorder (AUD) on risk of developing an adverse event (opioid use disorder, SREs, depression and death).
RESULTS
DeepBiomarker2 predicted whether a PTSD + AUD patient will have a diagnosis of any adverse events (SREs, opioid use disorder, depression, death) within 3 months with area under the receiver operator curve (AUROC) of 0.94. We found piroxicam, vilazodone, dronabinol, tenofovir, suvorexant, empagliflozin, famciclovir, veramyst, amantadine, sulfasalazine, and lamivudine to have potential to reduce risk.
CONCLUSIONS
DeepBiomarker2 can predict multiple adverse event risk with high accuracy and identify potential risk and beneficial factors. Our results offer suggestions for personalized interventions in a variety of clinical and diverse populations.
PubMed: 37790550
DOI: 10.21203/rs.3.rs-3299369/v1 -
RSC Advances Sep 2023Piroxicam and naproxen are well-known non-steroidal anti-inflammatory drugs that are frequently detected in aquatic environments due to their widespread usage and...
Piroxicam and naproxen are well-known non-steroidal anti-inflammatory drugs that are frequently detected in aquatic environments due to their widespread usage and improper disposal practices. This research investigates the photocatalytic degradation of these drugs by using CeO nanoparticles. The nanoparticles were synthesized by using plant extract and were characterized through various characterization techniques such as UV-visible spectroscopy, FTIR spectroscopy, SEM, EDX, and XRD. The photocatalytic degradation of piroxicam and naproxen using CeO nanoparticles led to the efficient removal of these pharmaceutical drugs in a short time duration with photodegradation efficiencies of 89% and 97% for naproxen and piroxicam, respectively. The photodegradation reaction was found to follow pseudo-order first-order kinetics. The recyclability of the catalyst was also studied for up to six cycles where the degradation efficiency was maintained at 100% till the 2nd cycle and was decreased by 11 and 13% for piroxicam and naproxen respectively after the 6th cycle. The current work focused on the achievement of sustainable development goals (SDGs) for water purification environmentally benign nanoparticles to remedy water pollution as it is the most prevalent issue in developed and underdeveloped countries throughout the world.
PubMed: 37746332
DOI: 10.1039/d3ra04185a -
Quantum Sensing for Real-Time Monitoring of Drug Efficacy in Synovial Fluid from Arthritis Patients.Nano Letters Sep 2023Diamond-based relaxometry is a new technique that allows nanoscale magnetic resonance measurements. Here we present its first application in patient samples. More...
Diamond-based relaxometry is a new technique that allows nanoscale magnetic resonance measurements. Here we present its first application in patient samples. More specifically, we demonstrate that relaxometry can determine the free radical load in samples from arthritis patients. We found that we can clearly differentiate between osteoarthritis and rheumatoid arthritis patients in both the synovial fluid itself and cells derived from it. Furthermore, we tested how synovial fluid and its cells respond to piroxicam, a common nonsteroidal anti-inflammatory drug (NSAID). It is known that this drug leads to a reduction in reactive oxygen species production in fibroblast-like synoviocytes (FLS). Here, we investigated the formation of free radicals specifically. While FLS from osteoarthritis patients showed a drastic decrease in the free radical load, cells from rheumatoid arthritis retained a similar radical load after treatment. This offers a possible explanation for why piroxicam is more beneficial for patients with osteoarthritis than those with rheumatoid arthritis.
Topics: Humans; Synovial Fluid; Synovial Membrane; Piroxicam; Cells, Cultured; Arthritis, Rheumatoid; Osteoarthritis; Fibroblasts
PubMed: 37676737
DOI: 10.1021/acs.nanolett.3c01506 -
European Journal of Pharmaceutical... Nov 2023
PubMed: 37673750
DOI: 10.1016/j.ejps.2023.106575 -
Cancers Aug 2023It was recently shown that targeting extracellular vimentin (eVim) is safe and effective in preclinical models. Here, we report the safety and efficacy in client-owned...
It was recently shown that targeting extracellular vimentin (eVim) is safe and effective in preclinical models. Here, we report the safety and efficacy in client-owned dogs with spontaneous bladder cancer of CVx1, an iBoost technology-based vaccine targeting eVim in combination with COX-2 inhibition. This was a single-arm prospective phase 1/2 study with CVx1 in 20 client-owned dogs with spontaneous UC which involved four subcutaneous vaccinations with CVx1 at 2-week intervals for induction of antibody titers, followed by maintenance vaccinations at 2-month intervals. Additionally, daily cyclooxygenase (COX)-2 inhibition with meloxicam was given. The response was assessed by antibody titers, physical condition, abdominal ultrasound and thorax X-ray. The primary endpoints were the development of antibody titers, as well as overall survival compared to a historical control group receiving carboplatin and COX-2 inhibition with piroxicam. Kaplan-Meier survival analysis was performed. All dogs developed antibodies against eVim. Titers were adequately maintained for the duration of this study. A median overall survival of 374 days was observed, which was 196 days for the historical control group ( < 0.01). Short-term grade 1-2 toxicity at the injection site and some related systemic symptoms peri-vaccination were observed. No toxicity was observed related to the induced antibody response. A limitation of this study is the single-arm prospective setting. CVx1 plus meloxicam consistently induced efficient antibody titers, was well tolerated and showed prolonged survival. The results obtained merit further development for human clinical care.
PubMed: 37568772
DOI: 10.3390/cancers15153958 -
International Journal of Pharmaceutics Aug 2023In nasal drug product development, screening studies are vital to select promising compounds or formulations. The Parallel Artificial Membrane Permeability Assay...
In nasal drug product development, screening studies are vital to select promising compounds or formulations. The Parallel Artificial Membrane Permeability Assay (PAMPA), a high throughput screening tool, has been applied to evaluate drug permeability across several barriers such as the skin or blood-brain barrier. Herein, a new nasal-PAMPA model was optimized to predict nasal permeability, using a biorelevant donor medium containing mucin. The apparent permeability (P) of 15 reference compounds was assessed in six different experimental conditions, and the most discriminating and predictive model was applied to a test drug (piroxicam) and mucoadhesive powder formulations loading the same drug. The model with 0.5% (w/v) mucin in the donor compartment and 2% (w/v) phosphatidylcholine in the lipid membrane accurately distinguished high and low permeable compounds. Additionally, it exhibited the highest correlation with permeation across human nasal epithelial cells, RPMI 2650 (R = 0.93). When applied to powder formulations, this model was sensitive to the presence of mucoadhesive excipients and the drug solid state. Overall, the nasal-PAMPA model was more rapid than cell-based assays, without requiring specialized training or equipment, showing to be a promising in vitro tool that can be applied in drug and formulation screening for nasal delivery.
Topics: Humans; Pharmaceutical Preparations; High-Throughput Screening Assays; Powders; Skin; Permeability; Membranes, Artificial
PubMed: 37479103
DOI: 10.1016/j.ijpharm.2023.123252 -
European Journal of Pharmacology Sep 2023Capsaicin and allyl isothiocyanate (AITC) activate transient receptor potential (TRP) vanilloid-1 (TRPV1) and TRP ankyrin-1 (TRPA1), respectively. TRPV1 and TRPA1...
Capsaicin and allyl isothiocyanate (AITC) activate transient receptor potential (TRP) vanilloid-1 (TRPV1) and TRP ankyrin-1 (TRPA1), respectively. TRPV1 and TRPA1 expression have been identified in the gastrointestinal (GI) tract. GI mucosal functions remain largely undefined for TRPV1 and TRPA1 with side-dependence and regional differences in signalling unclear. Here we investigated TRPV1- and TRPA1-induced vectorial ion transport as changes in short-circuit current (ΔI), in defined segments of mouse colon mucosa (ascending, transverse and descending) under voltage-clamp conditions in Ussing chambers. Drugs were applied basolaterally (bl) or apically (ap). Capsaicin responses were biphasic, with primary secretory and secondary anti-secretory phases, observed with bl application only, which predominated in descending colon. AITC responses were monophasic and secretory, with ΔI dependent on colonic region (ascending vs. descending) and sidedness (bl vs. ap). Aprepitant (neurokinin-1 (NK1) antagonist, bl) and tetrodotoxin (Na channel blocker, bl) significantly inhibited capsaicin primary responses in descending colon, while GW627368 (EP4 receptor antagonist, bl) and piroxicam (cyclooxygenase inhibitor, bl) inhibited AITC responses in ascending and descending colonic mucosae. Antagonism of the calcitonin gene-related peptide (CGRP) receptor had no effect on mucosal TRPV1 signalling, while tetrodotoxin and antagonists of the 5-hydroxytryptamine-3 and 4 receptors, CGRP receptor, and EP1/2/3 receptors had no effect on mucosal TRPA1 signalling. Our data demonstrates the regional-specificity and side-dependence of colonic TRPV1 and TRPA1 signalling, with involvement of submucosal neurons and mediation by epithelial NK1 receptor activation for TRPV1, and endogenous prostaglandins and EP4 receptor activation for TRPA1 mucosal responses.
Topics: Mice; Animals; Transient Receptor Potential Channels; TRPA1 Cation Channel; Capsaicin; Tetrodotoxin; Colon; Mucous Membrane; TRPV Cation Channels
PubMed: 37394028
DOI: 10.1016/j.ejphar.2023.175897 -
European Journal of Pharmaceutical... Sep 2023Semi-solid extrusion (SSE) 3D printing enables flexible designs and dose sizes to be printed on demand and is a suitable tool for fabricating personalized dosage forms....
Semi-solid extrusion (SSE) 3D printing enables flexible designs and dose sizes to be printed on demand and is a suitable tool for fabricating personalized dosage forms. Controlled Expansion of Supercritical Solution (CESS®) is a particle size reduction technology, and it produces particles of a pure active pharmaceutical ingredient (API) in a dry state, suspendable in the printing ink. In the current study, as a model API of poorly water-soluble drug, nanoformed piroxicam (nanoPRX) prepared by CESS® was accommodated in hydroxypropyl methylcellulose- or hydroxypropyl cellulose-based ink formulations to warrant the printability in SSE 3D printing. Importantly, care must be taken when developing nanoPRX formulations to avoid changes in their polymorphic form or particle size. Printing inks suitable for SSE 3D printing that successfully stabilized the nanoPRX were developed. The inks were printed into films with escalating doses with exceptional accuracy. The original polymorphic form of nanoPRX in the prepared dosage forms was not affected by the manufacturing process. In addition, the conducted stability study showed that the nanoPRX in the prepared dosage form remained stable for at least three months from printing. Overall, the study rationalizes that with nanoparticle-based printing inks, superior dose control for the production of personalized dosage forms of poorly water-soluble drugs at the point-of-care can be achieved.
Topics: Piroxicam; Printing, Three-Dimensional; Technology; Excipients; Water
PubMed: 37329925
DOI: 10.1016/j.ejps.2023.106497 -
JBRA Assisted Reproduction Sep 2023Endogenous prostaglandins are involved in hemostasis, renal excretion of electrolytes, and implicated in dysmenorrhea. Piroxicam and Nitroglycerin are common drugs used...
OBJECTIVE
Endogenous prostaglandins are involved in hemostasis, renal excretion of electrolytes, and implicated in dysmenorrhea. Piroxicam and Nitroglycerin are common drugs used in treating dysmenorrhea by inhibiting the cyclooxygenase pathway involved in prostaglandin production. However, studies comparing the effects of these drugs on prostaglandin-modulated hemostasis and renal function are lacking.
METHODS
Fifteen female rats (120-160g) were divided into 3 groups (20 per group), namely Control (distilled water, 0.3 mL), Piroxicam treated (3mg/kg) and Nitroglycerin treated (1 mg/kg). Di-estrous phase was confirmed in animals in each group using the Pipette smear method. Treatment was administered for 4 days covering the estrous cycle. Bleeding and clotting time were assessed and blood concentrations of sodium, potassium, urea and platelet counts were evaluated in all phases. Data were analyzed using one-way ANOVA and Newman-Keuls post-hoc test. Statistical significance was considered at p<0.0.
RESULTS
The nitroglycerin-treated group showed significant increases in blood potassium during di-estrous while the piroxicam-treated group showed significant increases in blood potassium, urea and clotting time with a significant decrease in sodium levels during di-estrous compared to controls. Results obtained in other phases were not significant compared to controls.
CONCLUSIONS
The study showed that Nitroglycerin produces minimum alteration of blood and electrolyte indices compared to piroxicam during di-estrous.
Topics: Humans; Female; Rats; Animals; Piroxicam; Rats, Wistar; Nitroglycerin; Cyclooxygenase Inhibitors; Prostaglandins; Dysmenorrhea; Urea; Sodium; Electrolytes; Potassium
PubMed: 37134015
DOI: 10.5935/1518-0557.20220069 -
Drug Delivery Dec 2023Cyclodextrin nanosponges are solid nanoparticles, designed by cross-linking of cyclodextrin polymer; it has been used widely as a good delivery system for water...
Cyclodextrin nanosponges are solid nanoparticles, designed by cross-linking of cyclodextrin polymer; it has been used widely as a good delivery system for water insoluble drugs. The aim of this study is to enhance the solubility of Piroxicam (PXM) using β-Cyclodextrin based nanosponges formulations. PXM nanosponge (PXM-NS) formulations were prepared using β-cyclodextrin and carbonyldiimidazole as a cross linker, three ratios of β-cyclodextrin to crosslinker in addition to three drug to nanosponges ratios were tested. Piroxicam nanosponge formulations were characterized for its particle size, zeta potential, physical compatibility and in vitro release. Stability studies at three temperatures (4 °C, 25 °C and 40 °C) were done for optimal formula. Finally, the in vivo analgesic activity and pharmacokinetic parameters of the optimal formula were conducted. The optimized PXM-NS formula (PXM-NS10) showed particle size (362 ± 14.06 nm), polydispersity index (0.0518), zeta potential (17 ± 1.05 mV), and %EE (79.13 ± 4.33). The dissolution study showed a significant increase in the amount of PXM dissolved compared with the unformulated drug. Stability studies confirmed that nanosponge showed accepted stability for 90 days at 4 °C and 25 °C. In vivo analgesic studies verified that there was a significant enhancement in the analgesic response to PXM in mice, and 1.42 fold enhancement in the relative bioavailability of PXM-NS10 as compared to commercial tablets. Nanosponge prepared under optimal conditions is an encouraging formula for increasing the solubility and therefore the bioavailability of Piroxicam.
Topics: Mice; Animals; Piroxicam; Drug Carriers; Solubility; beta-Cyclodextrins; Analgesics
PubMed: 36744372
DOI: 10.1080/10717544.2023.2174208