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Cureus Mar 2024This is a case of a 32-year-old woman, Gravida 3 para 2, previous two cesarean sections, who presented to our emergency department at 24+3 weeks of gestation complaining...
This is a case of a 32-year-old woman, Gravida 3 para 2, previous two cesarean sections, who presented to our emergency department at 24+3 weeks of gestation complaining of severe epigastric pain radiating to the back. She was diagnosed with severe hypertriglyceridemia complicated with acute pancreatitis and was managed by a multi-disciplinary team, which included obstetrics, gastroenterology, endocrinology, hematology, nutrition, and ICU team. Initially, conservative treatment was employed for her management. She was placed on nil per oral status and initiated on a normal saline infusion at a rate of 150 ml/hour, along with insulin infusion at 0.1 unit/kg/hour and dextrose (D5) at 80 ml/hour. Additionally, she received omeprazole, meropenem, clexane (40 mg once daily subcutaneous injection), iron, vitamin supplements, and analgesics as required. Subsequently, due to the failure of the initial conservative medical management, the patient was admitted to the ICU. Plasmapheresis was performed after the insertion of a vascath, using 3000 ml of albumin 5% as replacement fluid and oral calcium. Following this, she was prescribed Omacor (Omega 3) at a dosage of 2 grams orally twice daily, along with a low carbohydrate and fat diet, to manage her triglyceride levels. After the removal of the central line, her triglycerides increased to 14.3 mmol/L, leading to the initiation of fenofibrate at a daily dose of one tablet. With persistent elevation to 16.4 mmol/L, Lipitor at 40 mg once daily was introduced. Following this intervention, her triglyceride levels stabilized, and her overall condition improved. She was discharged at 25+1 weeks with a prescribed regimen, and scheduled follow-ups were arranged in the endocrine and obstetrics clinics. At 36 weeks of gestation, she presented to the emergency room with abdominal, back, and leg pain. Fetal distress, indicated by fetal tachycardia (170-180 bpm) on cardiotocography, prompted an urgent category 1 cesarean section, which proceeded without complications.
PubMed: 38606269
DOI: 10.7759/cureus.56006 -
JPMA. the Journal of the Pakistan... Mar 2024To compare the therapeutic efficacy and drug safety of Vonoprazan and Esomeprazole triple therapies in Helicobacter pylori infection. (Randomized Controlled Trial)
Randomized Controlled Trial
Therapeutic efficacy and drug safety comparison of one-week Vonoprazan triple therapy with two-weeks Esomeprazole triple therapy in Helicobacter pylori infection: Findings from a single-centre randomized clinical trial in population of Pakistan.
OBJECTIVE
To compare the therapeutic efficacy and drug safety of Vonoprazan and Esomeprazole triple therapies in Helicobacter pylori infection.
METHODS
The randomised clinical trial was conducted from December 2022 to January 2023 at the Department of Pharmacology, Army Medical College, National University of Medical Sciences, Rawalpindi, Pakistan, in collaboration with the Gastroenterology Department of Pak Emirates Military Hospital, Rawalpindi, and comprised patients found positive for Helicobacter pylori by stool antigen test. They were randomly distributed into two groups. The EAL group received twoweek triple therapy with Esomeprazole 20mgand Amoxicillin 1000mg twice daily with Levofloxacin 500mg once daily. The VAL group was prescribed one-week triple therapy with Vonoprazan 20mg and Amoxicillin 1000mg twice daily with Levofloxacin 500mg once daily. Eradication success was evaluated by stool antigen test 4 weeks after starting the treatment. Safety of the therapy was assessed by noting adverse effects at days 3 and 14 of the treatment. Data was analysed using SPSS 27.
RESULTS
Of the 122 patients, there were 61(50%) in each of the 2 groups; 30(49.2%) males and 31(50.8%) females with mean age 38.40±12.25 years in group EAL, and 35(57.4%) males and 26(42.6%) females with mean age 40.98±12.13 years in VAL group. In the EAL group, 57(93.4%) patients were found to be free of Helicobacter pylori infection compared to 58(95%) in the VAL group. Nausea 14(23%), bitter taste 41(67.2%), abdominal pain 16(26.2%) and headache 20(32.8%) were the adverse effects that were significantly more common in the EAL group compared to the VAL group B.
CONCLUSIONS
Vonoprazan-based triple therapy was found to be more effective with less reported adverse effects and potential benefits of better patient compliance due to shorter therapy duration.
CLINICAL TRIAL NUMBER
Iranian Registry of Clinical Trials: IRCT20221207056738N1.
Topics: Male; Female; Humans; Adult; Middle Aged; Helicobacter Infections; Esomeprazole; Levofloxacin; Anti-Bacterial Agents; Helicobacter pylori; Pakistan; Iran; Amoxicillin; Drug Therapy, Combination; Treatment Outcome; Clarithromycin; Proton Pump Inhibitors; Pyrroles; Sulfonamides
PubMed: 38591272
DOI: 10.47391/JPMA.9545 -
American Journal of Translational... 2024To investigate the efficacy and safety of tranexamic acid (TXA) in preventing upper gastrointestinal (GI) bleeding in patients with gastric cancer.
OBJECTIVE
To investigate the efficacy and safety of tranexamic acid (TXA) in preventing upper gastrointestinal (GI) bleeding in patients with gastric cancer.
METHODS
The clinical data of patients with gastric cancer complicated with acute non-operative GI bleeding treated in the Fourth Hospital of Hebei Medical University from 2020 to 2022 were collected and retrospectively analyzed. The survival status of the patients was followed up by telephone. The dataset of 168 patients was divided into a control group (n=85) and a TXA group (n=83), at a 1:1 ratio. The patients in the control group were treated with esomeprazole, and the patients in the TXA group received additional TXA. The hemostatic effect, rebleeding rate, and mortality of patients were compared between the two groups. The Cox proportional hazard model was used to evaluate the overall survival of patients as well as the related risk factors.
RESULTS
The success rate of hemostasis and the normal blood coagulation rate in the TXA group were significantly higher than those in the control group (P=0.003 and P=0.016). The secondary bleeding rate, thrombus formation rate and digestive tract perforation rate in the TXA group were significantly lower than those in the control group (P=0.002, P=0.003 and P=0.035). The improvement of all indicators in the TXA group was better than that in the control group (all P<0.05). For patients with gastric cancer complicated with acute GI bleeding treated with TXA, the Cox proportional hazard model identified III~IV stage, time of TXA treatment, surgical treatment after hemorrhage, and an increase of D-dimer as independent risk factors for upper GI bleeding (all P<0.05).
CONCLUSION
TXA can be an effective treatment for patients with gastric cancer complicated by GI bleeding.
PubMed: 38586096
DOI: 10.62347/KOLI5819 -
Gastroenterology Apr 2024High-dose proton pump inhibitor (PPI) therapy has been recommended to prevent rebleeding of high-risk peptic ulcer (PU) after hemostasis. Vonoprazan has been proven to...
Comparison of Vonoprazan vs Intravenous Proton Pump Inhibitor for Prevention of High-Risk Peptic Ulcers Rebleeding After Successful Endoscopic Hemostasis: A Multicenter Randomized Noninferiority Trial.
BACKGROUND & AIMS
High-dose proton pump inhibitor (PPI) therapy has been recommended to prevent rebleeding of high-risk peptic ulcer (PU) after hemostasis. Vonoprazan has been proven to be noninferior to PPIs in various acid-related diseases. This study aimed to compare the efficacy of vonoprazan vs PPI for preventing high-risk PU rebleeding after hemostasis.
METHODS
A multicenter, randomized, noninferiority study was conducted in 6 centers. Pre-endoscopic and endoscopic therapy were performed according to standard protocol. After successful hemostasis, patients with high-risk PU bleeding (Forrest class Ia/Ib, IIa/IIb) were randomized into 1:1 to receive vonoprazan (20 mg twice a day for 3 days, then 20 mg once a day for 28 days) or high-dose PPI (pantoprazole intravenous infusion 8 mg/h for 3 days, then omeprazole 20 mg twice a day for 28 days). The primary outcome was a 30-day rebleeding rate. Secondary outcomes included 3- and 7-day rebleeding rate, all-cause and bleeding-related mortality, rate of rescue therapy, blood transfusion, length of hospital stay, and safety.
RESULTS
Of 194 patients, baseline characteristics, severity of bleeding, and stage of ulcers were comparable between the 2 groups. The 30-day rebleeding rates in vonoprazan and PPI groups were 7.1% (7 of 98) and 10.4% (10 of 96), respectively; noninferiority (within 10% margin) of vonoprazan to PPI was confirmed (%risk difference, -3.3; 95% confidence interval, -11.2 to 4.7; P < .001). The 3-day and 7-day rebleeding rates in the vonoprazan group remained noninferior to PPI (P < .001 by Farrington and Manning test). All secondary outcomes were also comparable between the 2 groups.
CONCLUSION
In patients with high-risk PU bleeding, the efficacy of vonoprazan in preventing 30-day rebleeding was noninferior to intravenous PPI. (ClinicalTrials.gov, Number: NCT05005910).
PubMed: 38582271
DOI: 10.1053/j.gastro.2024.03.036 -
MethodsX Jun 2024Green analytical approaches are employed for the determination of active pharmaceutical ingredients, in conjunction with their impurities. Smart chemometric...
Greenness-sustainability metrics for assessment smart-chemometric spectrophotometric strategy for evaluation of the combination of six gastric proton-pump inhibitors with two selected impurities.
Green analytical approaches are employed for the determination of active pharmaceutical ingredients, in conjunction with their impurities. Smart chemometric spectrophotometric techniques, including orthogonal partial least square (OPLS), variable selection such as genetic algorithm (GA-OPLS), and interval selection (i-OPLS), were utilized. These chemometric models were implemented for assessing six proton-pump inhibitors Omeprazole, Esomeprazole, Lansoprazole, Pantoprazole, Rabeprazole, and Dexlansoprazole along with two selected official impurities, namely 4-Desmethoxy omeprazole impurity and Rabeprazole-impurity B. Experimental design was implemented to separate impurities, in the process of multivariate calibration, a five-level eight-factor calibration design consisting of 25 samples was selected. This design was deliberately selected to guarantee that the components were mutually orthogonal to assess the model's performance and reliability, a separate validation set of 15 samples was constructed. The best-performing of the proposed techniques were identified by considering the least favorable values of the Correlation Coefficient (R ≥ 0.9995), the Root Mean Square Error of Prediction (RMSEP) values between (0.0102-0.5622), and the Relative Error of Prediction (REP) values between (0.2961-1.1917). The proposed and reported methods' greenness-sustainability was quantitatively evaluated, and a comparative study of the greenness profile was established through a spider chart, the National Environmental Method Index tool, advanced and modified NEMI along with the Hexagon tool, and the whiteness qualities of the presented approaches were assessed by implementing the recently adopted Red-Green-Blue paradigm and White Analytical Chemistry tool. These approaches are well-suited for use in quality control laboratories due to their observed acceptance, long-term sustainability, simplicity, and affordability.
PubMed: 38577411
DOI: 10.1016/j.mex.2024.102670 -
Antimicrobial Agents and Chemotherapy May 2024The increasing prevalence of dermatophyte resistance to terbinafine, a key drug in the treatment of dermatophytosis, represents a significant obstacle to treatment. is...
The increasing prevalence of dermatophyte resistance to terbinafine, a key drug in the treatment of dermatophytosis, represents a significant obstacle to treatment. is the most commonly isolated fungus in dermatophytosis. In , we identified TERG_07844, a gene encoding a previously uncharacterized putative protein kinase, as an ortholog of budding yeast polyamine transport kinase 2 (Ptk2), and found that Ptk2 (TrPtk2) is involved in terbinafine tolerance. In both and , Ptk2 knockout strains were more sensitive to terbinafine compared with the wild types, suggesting that promotion of terbinafine tolerance is a conserved function of fungal Ptk2. Pma1 is activated through phosphorylation by Ptk2 in . Overexpression of Pma1 (TrPma1) in Ptk2 knockout strain (ΔTrPtk2) suppressed terbinafine sensitivity, suggesting that the induction of terbinafine tolerance by TrPtk2 is mediated by TrPma1. Furthermore, omeprazole, an inhibitor of plasma membrane proton pump Pma1, increased the terbinafine sensitivity of clinically isolated terbinafine-resistant strains. These findings suggest that, in dermatophytes, the TrPtk2-TrPma1 pathway plays a key role in promoting intrinsic terbinafine tolerance and may serve as a potential target for combinational antifungal therapy against terbinafine-resistant dermatophytes.
Topics: Terbinafine; Antifungal Agents; Saccharomyces cerevisiae; Drug Resistance, Fungal; Microbial Sensitivity Tests; Arthrodermataceae; Fungal Proteins; Proton-Translocating ATPases; Saccharomyces cerevisiae Proteins; Phosphorylation
PubMed: 38567956
DOI: 10.1128/aac.01609-23 -
Frontiers in Pediatrics 2024Eosinophilic esophagitis (EoE) is a chronic, immune-mediated inflammation of the esophagus, characterized by symptoms related to esophageal dysfunction, resulting from...
INTRODUCTION
Eosinophilic esophagitis (EoE) is a chronic, immune-mediated inflammation of the esophagus, characterized by symptoms related to esophageal dysfunction, resulting from severe eosinophilic infiltration of the esophageal mucosa. It is common in atopic subjects and food antigens have been identified as the most common triggers. However, a seasonal variation in EoE prevalence, correlated with air pollen levels, is reported, suggesting that also aeroallergens may play a role. Little is known about the interplay between EoE and concomitant atopy treatment for aeroallergens.
CASE PRESENTATION
We describe the case of an 11-year-old boy who presented dysphagia, vomiting, drooling, and chest pain while eating meat, developed 15 months after receiving sublingual immunotherapy (SLIT) for Alternaria (SUBLIVAC®). He underwent esophagogastroduodenoscopy (EGD) revealing severe eosinophilic predominant inflammation (100 eos/HPF), consistent with the diagnosis of EoE, not improving at the EGDs performed after both omeprazole and topical corticosteroids treatment, despite symptom improvement. Afterward, immunotherapy was switched from sublingual to injective form. At the EGD performed 1 month later, macroscopic examination of the esophageal mucosa was normal and eosinophilic infiltration was significantly decreased (5-10 eos/HPF).
CONCLUSIONS
SLIT may induce EoE by chronic antigenic exposure of oral mucosa in patients with a robust allergic susceptibility: while attenuating the IgE-mediated immune reactions, the progressive contact with the causative allergen might induce a chronic stimulation of the immune system with the consequent activation of tissue eosinophils. Our data suggest monitoring patients receiving SLIT for EoE symptoms and to discontinue SLIT on their earlier appearance, possibly as a first-line treatment.
PubMed: 38567182
DOI: 10.3389/fped.2024.1379162 -
Journal of Inflammation Research 2024Gastric ulcers pose a significant health risk due to an imbalance between protective and aggressive factors on the mucous membrane. Nonsteroidal anti-inflammatory drug...
BACKGROUND
Gastric ulcers pose a significant health risk due to an imbalance between protective and aggressive factors on the mucous membrane. Nonsteroidal anti-inflammatory drug (NSAID)-induced gastric damage affects 25% of users. Quinoxaline compounds, known for their diverse biological properties, have potential applications in cancer therapy and as antimicrobial agents targeting various pathogens.
OBJECTIVE
Our study aimed to investigate the impact of DMQ on gastroprotective mechanisms in an experimental model of indomethacin-induced gastric ulcer.
METHODS
Thirty male Wistar rats were randomly assigned to five groups. Group 1 served as the control, while Group 2 received a single oral dose of IND (30 mg/kg). Groups 3 and 4 received oral DMQ (30 mg/kg and 60 mg/kg, respectively) for three days, with the final dose administered intragastrically one hour before IND administration. Group 5 received esomeprazole (30 mg/kg) orally for three days, with the final dose given one hour before IND administration. Rats were sacrificed four hours after IND induction.
RESULTS
Indomethacin-induced ulcers were associated with epithelial damage and blood streaks on the gastric mucosa. However, DMQ significantly decreased levels of inflammatory biomarkers (TNF-α, IL-6, Cox-2, IFN-γ, and IL-β1) while increasing gastroprotective mediator prostaglandin E2 (PGE2) and mucin levels. Histopathological analysis revealed a significant reduction in ulcer-induced pathological alterations and upregulation of tumor suppressor genes (NF-κB levels) following DMQ treatment. Rats treated with Indo+DMQ showed a significant decrease in ulcer index compared to the Indo group, with mild injuries observed.
CONCLUSION
DMQ demonstrated promising gastroprotective effects against IND-induced gastric ulcers, as evidenced by alterations in histopathological data and upregulation of gene expression.
PubMed: 38566982
DOI: 10.2147/JIR.S453425 -
Endocrine Practice : Official Journal... Jun 2024This study evaluates the impact of a representative proton pump inhibitor (PPI) (omeprazole), administered simultaneously or staggered, on the pharmacokinetics of... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
This study evaluates the impact of a representative proton pump inhibitor (PPI) (omeprazole), administered simultaneously or staggered, on the pharmacokinetics of levothyroxine (LT4) solution (Tirosint-SOL).
METHODS
This was a randomized, 3-way crossover, comparative bioavailability study in 36 healthy adults under fasting conditions. Omeprazole 40 mg delayed-release capsule was administered once daily from Day 1 to 6 (mornings, Treatment-A; evenings, Treatment-B; none, Treatment-C) to increase and stabilize gastric pH. In the morning of Day 5, a single dose of LT4 solution 600 mcg was administered. Blood samples were collected 0 to 48 hours post-LT4 administration. Noncompartmental pharmacokinetic parameters were calculated for total serum thyroxine using baseline-corrected data. Maximum concentration (C) and area under the concentration-time curve (AUC) were included in an analysis of variance to obtain geometric mean ratios and 90% confidence intervals.
RESULTS
For both comparisons (A/C and B/C), geometric mean ratios and 90% confidence intervals for all parameters were within the equivalence boundaries (80%-125%), indicating bioequivalence: for A/C, AUC 98.98% [94%-104%], and C 91.68% [87%-97%]; for B/C, AUC 98.94% [95%-103%], and C 94.90% [90%-100%]. Median T (time associated with Cmax) was similar across treatments.
CONCLUSION
This study demonstrated that Tirosint-SOL bioavailability is unaffected by coadministration of a representative PPI, given simultaneously or staggered by about 12 hours, compared to administration of LT4 solution alone. For hypothyroid patients on PPI therapy, administration of LT4 solution may reduce variations in thyroid stimulating hormone levels related to intermittent use of acid-reducing drugs and consequently the need for dose adjustments.
Topics: Humans; Proton Pump Inhibitors; Male; Thyroxine; Adult; Biological Availability; Cross-Over Studies; Female; Middle Aged; Omeprazole; Young Adult; Drug Interactions
PubMed: 38554774
DOI: 10.1016/j.eprac.2024.03.388 -
European Journal of Drug Metabolism and... May 2024Abrocitinib is an oral small-molecule Janus kinase (JAK)-1 inhibitor approved for the treatment of moderate-to-severe atopic dermatitis. In vitro studies indicated that...
Assessment of the Effects of Abrocitinib on the Pharmacokinetics of Probe Substrates of Cytochrome P450 1A2, 2B6 and 2C19 Enzymes and Hormonal Oral Contraceptives in Healthy Individuals.
BACKGROUND AND OBJECTIVE
Abrocitinib is an oral small-molecule Janus kinase (JAK)-1 inhibitor approved for the treatment of moderate-to-severe atopic dermatitis. In vitro studies indicated that abrocitinib is a weak time-dependent inhibitor of cytochrome P450 (CYP) 2C19/3A and a weak inducer of CYP1A2/2B6/2C19/3A. To assess the potential effect of abrocitinib on concomitant medications, drug-drug interaction (DDI) studies were conducted for abrocitinib with sensitive probe substrates of these CYP enzymes. The impact of abrocitinib on hormonal oral contraceptives (ethinyl estradiol and levonorgestrel), as substrates of CYP3A and important concomitant medications for female patients, was also evaluated.
METHODS
Three Phase 1 DDI studies were performed to assess the impact of abrocitinib 200 mg once daily (QD) on the probe substrates of: (1) 1A2 (caffeine), 2B6 (efavirenz) and 2C19 (omeprazole) in a cocktail study; (2) 3A (midazolam); and (3) 3A (oral contraceptives).
RESULTS
After multiple doses of abrocitinib 200 mg QD, there is a lack of effect on the pharmacokinetics of midazolam, efavirenz and contraceptives. Abrocitinib increased the area under the concentration time curve from 0 to infinity (AUC) and the maximum concentration (C) of omeprazole by approximately 189 and 134%, respectively. Abrocitinib increased the AUC of caffeine by 40% with lack of effect on C.
CONCLUSIONS
Based on the study results, abrocitinib is a moderate inhibitor of CYP2C19. Caution should be exercised when using abrocitinib concomitantly with narrow therapeutic index medicines that are primarily metabolized by CYP2C19 enzyme. Abrocitinib is a mild inhibitor of CYP1A2; however, the impact is not clinically relevant, and no general dose adjustment is recommended for CYP1A2 substrates. Abrocitinib does not inhibit CYP3A or induce CYP1A2/2B6/2C19/3A and does not affect the pharmacokinetics of contraceptives.
CLINICAL TRIALS REGISTRATION
ClinicalTrials.gov registration IDs: NCT03647670, NCT05067439, NCT03662516.
Topics: Humans; Female; Drug Interactions; Adult; Young Adult; Pyrimidines; Cytochrome P-450 CYP1A2; Male; Ethinyl Estradiol; Healthy Volunteers; Contraceptives, Oral, Hormonal; Cytochrome P-450 CYP2C19; Levonorgestrel; Contraceptives, Oral, Combined; Middle Aged; Area Under Curve; Drug Combinations; Sulfonamides
PubMed: 38554232
DOI: 10.1007/s13318-024-00893-5