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International Urogynecology Journal Sep 2022To determine if administration of a standard 400 mg oral dose of riboflavin (vitamin B2) was comparable to phenazopyridine (pyridium) for evaluating ease of... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION AND HYPOTHESIS
To determine if administration of a standard 400 mg oral dose of riboflavin (vitamin B2) was comparable to phenazopyridine (pyridium) for evaluating ease of visualization of ureteral jets at the time of cystoscopy.
METHODS
A three-arm double-blinded, randomized controlled study was performed consisting of thiamine as placebo, phenazopyridine, and riboflavin. Agents were administered the morning of surgery prior to surgical procedure. The primary outcome was the ease of visualization of the ureteral jets based on a grading of urine stain intensity on a 7-point color scale, where 1-2 were minimal yellow staining, 3-4 were moderate yellow staining, and 5-7 defined as intense yellow staining. Analysis of covariance (ANCOVA) was used with pairwise comparison to characterize urine stain intensity as a continuous variable among the three groups controlling for age, BMI, creatinine, and time from ingestion of medication to first cystoscopy.
RESULTS
Eighty-four subjects were randomized with a mean ± SD age of 46.25 + 11.36 and BMI of 32.46 + 6.59. Riboflavin did have moderate or intense staining in 57% of cases; however, there was no significant difference between urine staining intensity compared to placebo (p = 0.21). There was a statistically significant increased urine staining intensity for phenazopyridine compared to placebo (p = 0.001) and for phenazopyridine compared to riboflavin (p = 0.001).
CONCLUSIONS
Phenazopyridine provided statistically significantly greater urine staining compared to both riboflavin and placebo and should be considered primarily for ease of ureteral jet visualization.
Topics: Administration, Oral; Coloring Agents; Humans; Phenazopyridine; Riboflavin; Staining and Labeling; Ureter
PubMed: 34057543
DOI: 10.1007/s00192-021-04867-y -
The Journal of Emergency Medicine Aug 2021Sulfhemoglobinemia is a rare dyshemoglobinemia that presents similarly to methemoglobinemia.
BACKGROUND
Sulfhemoglobinemia is a rare dyshemoglobinemia that presents similarly to methemoglobinemia.
CASE REPORT
An 83-year-old woman with stage IV ovarian cancer presented to the Emergency Department after a near syncopal spell and was found to be cyanotic with a pulse oximetry reading of 71%. Pulse oximetry improved to only the mid-80s range with administration of high-flow oxygen. Her arterial blood gas on supplemental high-flow oxygen demonstrated a PaO of 413 mm Hg and methemoglobin of 1.2%, but also noted the interference of the co-oximetry with sulfhemoglobinemia. Further history revealed that the patient had recently been started on phenazopyridine. The phenazopyridine was stopped, an exchange transfusion was offered but declined, and the patient was discharged to home hospice. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The diagnosis of sulfhemoglobinemia can be challenging given that routine co-oximetry does not identify it. The clue to the diagnosis is that the cyanotic-appearing patient has a normal or elevated PaO and seems to be less ill than expected, given the degree of cyanosis. Sulfhemoglobinemia does not reverse with the administration of methylene blue.
Topics: Aged, 80 and over; Cyanosis; Dyspnea; Female; Humans; Methemoglobinemia; Methylene Blue; Oximetry; Phenazopyridine; Sulfhemoglobinemia
PubMed: 34034895
DOI: 10.1016/j.jemermed.2021.03.002 -
Urology Aug 2021To determine the true failure rate of opioid free ureteroscopy (OF-URS) and rates of new-persistent opioid use utilizing a national prescription drug monitoring program.
OBJECTIVE
To determine the true failure rate of opioid free ureteroscopy (OF-URS) and rates of new-persistent opioid use utilizing a national prescription drug monitoring program.
MATERIAL AND METHODS
We identified 239 patients utilizing our retrospective stone database who underwent OF-URS from Februrary 2018-March 2020. In Feb 2018, we initiated a OF-URS pathway (diclofenac, tamsulosin, acetaminophen, pyridium and oxybutynin). Patients who had a contraindication to NSAIDs were excluded from primary analyses. A prescription drug monitoring program was then utilized to determine the number of patients who failed OF-URS (defined as receipt of an opioid within 31 days of surgery) as well as rates of new-persistent opioid use (defined as receipt of opioid 91-180 days after surgery). All statistical analyses were performed using SAS 9.4. Tests were 2-sided and statistical significance was set at P<0.05.
RESULTS
We found a OF-URS failure rate of 16.6% and 14.0% in the total and opioid naïve cohorts, respectively. Rates of new-persistent opioid use were 0.9% and 1.2%, respectively (lower than published expected rate of ~6% after URS with postoperative opioids). 91% of patients obtained opioid from alternative sources. Uni/multivariate analyses were performed for both cohorts. In the total cohort, benzodiazepine users had a lower risk of OF-URS failure on multivariate analysis. No variables were associated with OF-URS failure in the opioid naïve cohort.
CONCLUSION
The true failure rate of OF-URS is higher than previously thought at 16.6% and 14.0%. However, efforts to reduce opioid prescriptions with OF-URS pathways have successfully reduced new-persistent opioid use.
Topics: Acetaminophen; Analgesics, Non-Narcotic; Analgesics, Opioid; Diclofenac; Drug Prescriptions; Female; Humans; Kidney Calculi; Male; Mandelic Acids; Middle Aged; Pain, Postoperative; Phenazopyridine; Retrospective Studies; Tamsulosin; Ureteroscopy
PubMed: 33774043
DOI: 10.1016/j.urology.2021.03.011 -
Fundamental & Clinical Pharmacology Dec 2021The nonclinical branch of regulatory pharmacology has traditionally relied on the sensitivity and specificity of regulatorily recommended bioassays. Nonetheless, any...
The nonclinical branch of regulatory pharmacology has traditionally relied on the sensitivity and specificity of regulatorily recommended bioassays. Nonetheless, any predictive testing (eg, safety pharmacology) with less than 100% sensitivity or 100% specificity is prone to deliver false positive or negative results (namely, outcomes discordant to the clinical gold standard). It was recently suggested that the statistics-based and regulatory pertinent "predictive values approach" (PVA) might help to reach a more predictive use of preclinical testing data. To resolve the associated probability of carcinogenicity to humans, the PVA was applied to 37 pharmaceuticals bearing inadequate epidemiological evidence of carcinogenicity, but identifiable as unequivocal mutagens. According to current knowledge, a 98.9% (or more) probability of carcinogenicity to humans was reckoned for those 37 genotoxic drugs. Accordingly, these pharmaceutical drugs might be either scientifically or regulatorily regarded as "carcinogenic to humans." In the USA, European Union, or Canada as examples, the great majority of these 37 pharmaceuticals are authorized for medical use in humans. From the results of the present appraisal, the following is suggested (1) for the pharmaceuticals listed in this report, to include significant carcinogenicity warnings in their prescribing information; (2) to conduct pharmacoepidemiology studies or risk-benefit analyses (if warranted), and (3) based on the respective risk-benefit analyses, to re-evaluate the authorization of hydralazine and phenoxybenzamine as antihypertensives, oxcarbazepine as an anticonvulsant, and phenazopyridine as a urinary tract antimicrobial or analgesic. For the four latter drugs (eg, phenoxybenzamine), a 99.5% probability of carcinogenicity to humans was estimated.
Topics: Alkylating Agents; Carcinogenicity Tests; Carcinogens; DNA; Humans; Intercalating Agents; Mutagenicity Tests; Pharmaceutical Preparations; Poisons; Probability; Topoisomerase Inhibitors
PubMed: 33772863
DOI: 10.1111/fcp.12674 -
International Urogynecology Journal Jun 2021
Topics: Anesthetics, Local; Humans; Phenazopyridine; Preoperative Care; Urinary Retention
PubMed: 33595673
DOI: 10.1007/s00192-021-04722-0 -
International Urogynecology Journal Mar 2022Previous studies have found that administration of phenazopyridine decreased short-term urinary retention following surgery but other more recent trials have shown mixed...
INTRODUCTION AND HYPOTHESIS
Previous studies have found that administration of phenazopyridine decreased short-term urinary retention following surgery but other more recent trials have shown mixed results. This study sought to investigate the potential benefit of preoperative administration of oral phenazopyridine in relation to the prevention of short-term urinary retention following urogynecologic surgery.
METHODS
This is a retrospective cohort study of a convenience sample of women undergoing urogynecologic surgery from June 2016 to March 2019. Following surgery, subjects underwent a standardized retrograde voiding trial. The data had previously been gathered from a prior prospective trial at our institution (Kesty et al. Int Urogynecol J 31(9):1899-1905, 11). Chart review was performed to determine whether patients that received 200 mg of preoperative oral phenazopyridine to better visualize ureteral efflux during cystourethroscopy were more or less likely to pass their postoperative voiding trial. Bivariate statistical analysis was performed as well as a multivariate logistic regression model.
RESULTS
A total of 165 subjects were included in the final analysis; 100 who did not receive preoperative phenazopyridine and 65 who did receive phenazopyridine. There was no statistical difference between voiding trial pass rates following urogynecologic surgery between those who did not receive preoperative phenazopyridine compared to those who did [77% (77/100) and 82% (53/65), respectively, p = 0.37)]. The multivariate logistic regression model demonstrated no difference in postoperative voiding trial pass rates among those who received preoperative phenazopyridine compared to those who did not (OR 1.7, 95% CI: 0.53, 5.8).
CONCLUSIONS
Preoperative administration of oral phenazopyridine does not decrease short-term urinary retention following urogynecologic surgery.
Topics: Clinical Trials as Topic; Cystoscopy; Female; Humans; Phenazopyridine; Postoperative Complications; Prospective Studies; Retrospective Studies; Urinary Retention
PubMed: 33580812
DOI: 10.1007/s00192-021-04699-w -
Journal of Hazardous Materials Jun 2021High-performance novel iron oxyhydroxide (limonite) nanostructure, with improved surface reactive sites, was prepared via one-pot, eco-friendly, free precursor and cold...
Efficient oxidation/mineralization of pharmaceutical pollutants using a novel Iron (III) oxyhydroxide nanostructure prepared via plasma technology: Experimental, modeling and DFT studies.
High-performance novel iron oxyhydroxide (limonite) nanostructure, with improved surface reactive sites, was prepared via one-pot, eco-friendly, free precursor and cold glow discharge N-plasma technique. Natural and plasma treated (PTNL/N) limonite samples were characterized by FESEM, XPS, XRD, FTIR, AAS, EDX, BET/BJH and pH to confirm the successful synthesis. Central composite design (CCD) and artificial neural network (ANN, topology of 4:8:1) methods were utilized to study the oxidation/mineralization of phenazopyridine (PhP) as a hazardous contaminant by heterogeneous catalytic ozonation process (HCOP). The obtained results indicated that PTNL/N had the highest catalytic performance in PhP degradation (98.6% in 40 min) and mineralization (80.4% in 120 min). The degradation mechanism in different processes was investigated by dissolved ozone concentration, various organic scavengers (BQ and TBA) and inorganic salts (NaNO, NaCl, NaCO and NaHPO). Moreover, reusability-stability, Fe and nitrogen (NO and NH) ions release were assessed during different AOPs. Furthermore, toxicity tests indicated that the HCOP using PTNL/N was able to detoxify the PhP solutions efficiently. Finally, Density Functional Theory (DFT) studies were employed to introduce the most plausible contaminant degradation pathway, reactive sites and byproducts. This research provided a new insight into the improvement of wastewater treatment studies by a combination of experiment and computer simulation.
PubMed: 33461011
DOI: 10.1016/j.jhazmat.2021.125074 -
Scientific Reports Jan 2021The present study has focused on the degradation of phenazopyridine (PhP) as an emerging contaminant through catalytic ozonation by novel plasma treated natural limonite...
The present study has focused on the degradation of phenazopyridine (PhP) as an emerging contaminant through catalytic ozonation by novel plasma treated natural limonite (FeOOH·xHO, NL) under argon atmosphere (PTL/Ar). The physical and chemical characteristics of samples were evaluated with different analyses. The obtained results demonstrated higher surface area for PTL/Ar and negligible change in crystal structure, compared to NL. It was found that the synergistic effect between ozone and PTL/Ar nanocatalyst was led to highest PhP degradation efficiency. The kinetic study confirmed the pseudo-first-order reaction for the PhP degradation processes included adsorption, peroxone and ozonation, catalytic ozonation with NL and PTL/Ar. Long term application (6 cycles) confirmed the high stability of the PTL/Ar. Moreover, different organic and inorganic salts as well as the dissolved ozone concentration demonstrated the predominant role of hydroxyl radicals and superoxide radicals in PhP degradation by catalytic Ozonation using PTL/Ar. The main produced intermediates during PhP oxidation by PTL/Ar catalytic ozonation were identified using LC-(+ESI)-MS technique. Finally, the negligible iron leaching, higher mineralization rate, lower electrical energy consumption and excellent catalytic activity of PTL/Ar samples demonstrate the superior application of non-thermal plasma for treatment of NL.
PubMed: 33441829
DOI: 10.1038/s41598-020-80200-9 -
American Journal of Therapeutics Dec 2020Recognition of the agents most commonly implicated in causing methemoglobinemia can provide context for making therapeutic decisions and inform the diagnostic process....
BACKGROUND
Recognition of the agents most commonly implicated in causing methemoglobinemia can provide context for making therapeutic decisions and inform the diagnostic process. We evaluated the etiologic agents most commonly implicated in clinically significant methemoglobinemia using data from the National Poison Data System (NPDS).
STUDY QUESTION
What are the most frequent etiologic agents associated with clinically significant methemoglobinemia.
STUDY DESIGN
This was a retrospective cross-sectional chart review using electronic data from the NPDS. The NPDS database was queried to identify cases from July 1, 2007, to June 30, 2017, that were coded as methylene blue treatment recommended and/or performed. Cases were excluded if the substance(s) have never been known to cause methemoglobin or the substances suggested methylene blue was used adjunctively for refractory shock (eg, calcium channel or beta blocker). Multiple substance exposures were reviewed and substances not known to cause methemoglobinemia were excluded.
MEASURES AND OUTCOMES
The primary end point was to summarize the most frequent etiologic agents associated with the administration of methylene blue for clinically significant methemoglobinemia.
RESULTS
There were 2563 substances reported in 1209 cases. After excluding coingestants and cases not associated with methemoglobinemia, there were 1236 substances. The top 4 substance categories were benzocaine, phenazopyridine, dapsone, and nitrates/nitrites.
CONCLUSIONS
This study reveals the relative contribution of various drugs and chemicals associated with methylene blue administration. Over two-thirds of all cases were associated with benzocaine, phenazopyridine, dapsone, and nitrates/nitrites.
Topics: Benzocaine; Cross-Sectional Studies; Humans; Methemoglobinemia; Methylene Blue; Poisons; Retrospective Studies
PubMed: 33416248
DOI: 10.1097/MJT.0000000000001277 -
ChemMedChem Apr 2021Rev1 is a protein scaffold of the translesion synthesis (TLS) pathway, which employs low-fidelity DNA polymerases for replication of damaged DNA. The TLS pathway helps...
Rev1 is a protein scaffold of the translesion synthesis (TLS) pathway, which employs low-fidelity DNA polymerases for replication of damaged DNA. The TLS pathway helps cancers tolerate DNA damage induced by genotoxic chemotherapy, and increases mutagenesis in tumors, thus accelerating the onset of chemoresistance. TLS inhibitors have emerged as potential adjuvant drugs to enhance the efficacy of first-line chemotherapy, with the majority of reported inhibitors targeting protein-protein interactions (PPIs) of the Rev1 C-terminal domain (Rev1-CT). We previously identified phenazopyridine (PAP) as a scaffold to disrupt Rev1-CT PPIs with Rev1-interacting regions (RIRs) of TLS polymerases. To explore the structure-activity relationships for this scaffold, we developed a protocol for co-crystallization of compounds that target the RIR binding site on Rev1-CT with a triple Rev1-CT/Rev7 /Rev3-RBM1 complex, and solved an X-ray crystal structure of Rev1-CT bound to the most potent PAP analogue. The structure revealed an unexpected binding pose of the compound and informed changes to the scaffold to improve its affinity for Rev1-CT. We synthesized eight additional PAP derivatives, with modifications to the scaffold driven by the structure, and evaluated their binding to Rev1-CT by microscale thermophoresis (MST). Several second-generation PAP derivatives showed an affinity for Rev1-CT that was improved by over an order of magnitude, thereby validating the structure-based assumptions that went into the compound design.
Topics: Dose-Response Relationship, Drug; Drug Design; Enzyme Inhibitors; Humans; Molecular Structure; Nucleotidyltransferases; Phenazopyridine; Structure-Activity Relationship
PubMed: 33314657
DOI: 10.1002/cmdc.202000893