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European Urology Focus Jul 2023The rise in antimicrobial resistance means that alternative approaches for the treatment and prevention of urinary tract infection (UTIs) are required. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The rise in antimicrobial resistance means that alternative approaches for the treatment and prevention of urinary tract infection (UTIs) are required.
OBJECTIVE
To evaluate the safety and efficacy of a D-mannose-based dietary supplement (D-mannose, citric acid, prebiotic fibers, Astragalus, and dandelion; DAPAD complex) for the treatment of uncomplicated acute E. coli UTIs.
DESIGN, SETTING, AND PARTICIPANTS
This was a single-center, randomized, double-blind, placebo-controlled trial conducted from April 2021 to October 2021 in Rajalakshmi Hospital and Research Centre (Bangalore, India). The participants were nonmenopausal women with an acute uncomplicated E. coli UTI. UTI was diagnosed according to the presence of at least one urinary symptom and bacteriuria (>100 000 CFU/ml).
INTERVENTION
The DAPAD complex was administered twice a day for 5 d, with phenazopyridine and alkalizing agents as the standard of care (SOC). The control group received placebo with SOC.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
Subjective (clinical resolution/response) and objective (midstream bacteriuria) outcomes were evaluated at the end of therapy (day 6) and at day 35 of follow-up. Adverse events were recorded. Categorical variables were analyzed using χ and Fisher's exact tests; a p value <0.05 was considered significant.
RESULTS AND LIMITATIONS
Seventy women were enrolled and equally randomized to the two groups. Clinical resolution was higher in the DAPAD group at 6 d (34.3% vs 0%; p < 0.0001) and 35 d from baseline (88.6% vs 20%, p < 0.0001). At day 35, no patients in the DAPAD group had moderate or severe symptoms, whereas 25.7% (nine/35) and 11.4% (four/35) of patients in the placebo group had moderate and severe symptoms, respectively. Bacteriological resolution was also higher in the DAPAD group at day 6 (85.7% vs 14.3%; p < 0.0001) and day 35 (100% vs 40%; p < 0.0001). Three mild adverse events (4.26%) unrelated to the investigated product were recorded, all of which were medically treated.
CONCLUSIONS
The DAPAD complex dietary supplement is effective and safe for treatment of acute uncomplicated E. coli UTIs.
PATIENT SUMMARY
Our results show that for nonmenopausal women with an uncomplicated Escherichia coli urinary tract infection, those treated with a dietary supplement (containing D-mannose, citric acid, prebiotic fibers, Astragalus, and dandelion) had a higher rate of clinical resolution or response than women who received a placebo.
Topics: Female; Humans; Mannose; Bacteriuria; Escherichia coli; Treatment Outcome; India; Urinary Tract Infections; Escherichia coli Infections; Dietary Supplements; Prebiotics
PubMed: 36621376
DOI: 10.1016/j.euf.2022.12.013 -
Food and Chemical Toxicology : An... Aug 2023Azo compounds are widely distributed synthetic chemicals in the modern world. Their most important applications are as dyes, but, in addition, several azo compounds are... (Review)
Review
Azo compounds are widely distributed synthetic chemicals in the modern world. Their most important applications are as dyes, but, in addition, several azo compounds are used as pharmaceuticals. Ingested azo compounds can be reduced by the action of bacteria in the gut, where the oxygen tension is low, and the development of microbiome science has allowed more precise delineation of the roles of specific bacteria in these processes. Reduction of the azo bond of an azo compound generates two distinct classes of aromatic amine metabolites: the starting material that was used in the synthesis of the azo compound and a product which is formed de novo by metabolism. Reductive metabolism of azo compounds can have toxic consequences, because many aromatic amines are toxic/genotoxic. In this review, we discuss aspects of the development and application of azo compounds in industry and medicine. Current understanding of the toxicology of azo compounds and their metabolites is illustrated with four specific examples - Disperse Dyes used for dyeing textiles; the drugs phenazopyridine and eltrombopag; and the ubiquitous food dye, tartrazine - and knowledge gaps are identified. SUBMISSION TO: FCT VSI: Toxicology of Dyes.
Topics: Azo Compounds; Coloring Agents; Tartrazine; Bacteria; Amines
PubMed: 37451600
DOI: 10.1016/j.fct.2023.113932 -
Obstetrics and Gynecology Feb 2024To assess and compile the current level of evidence regarding successful surgical treatment of vesicovaginal fistulae and how these perioperative interventions affect...
OBJECTIVE
To assess and compile the current level of evidence regarding successful surgical treatment of vesicovaginal fistulae and how these perioperative interventions affect anatomic, patient-centered, and adverse outcomes.
DATA SOURCES
PubMed and EMBASE were searched from inception through September 9, 2022.
METHODS OF STUDY SELECTION
This review included comparative studies (of any sample size) and single-group studies (1,000 or more participants) of primary or recurrent vesicovaginal fistula (ie, vesicovaginal fistula, urethrovaginal fistula, and bladder neck-vaginal fistula). We evaluated preintervention assessment or management, various techniques for intraoperative management, and postoperative management. Outcomes of interest included anatomic and objective outcomes (such as successful repair, fistula closure, urinary incontinence, recurrent fistula, perioperative complications) and subjective outcomes (such as voiding symptoms and quality of life). Abstracts and full-text articles were screened in duplicate, and study descriptions and findings were extracted into standardized extraction forms. Risk of bias was assessed independently by two investigators and adjudicated by a third. Study quality was summarized with standardized tools. We conducted random-effects model and restricted maximum-likelihood meta-analyses of relative risks when at least three studies compared similar interventions and reported similar outcome measures.
TABULATION, INTEGRATION, AND RESULTS
Forty-six studies met the inclusion criteria. Studies were categorized into 11 domains: 1) preoperative assessment, 2) preoperative and postoperative physical therapy, 3) route of surgery, 4) incorporation of a flap, 5) trimming, 6) layered closure, 7) intraoperative antibiotics, 8) fibrin glue, 9) fascial sling, 10) postoperative Foley catheter duration, and 11) quality of life. Although the strength of the data is insufficient, preoperative phenazopyridine, physical therapy, layered closure, and intraoperative antibiotics seemed to improve the rate of successful fistula repair. Route of surgery (vaginal vs abdominal laparotomy) was determined primarily by surgeon preference and showed no difference in successful fistula repair. In addition, use of interpositional flaps, trimming fistula edges, fibrin glue, and fascial sling did not show significant improvement in rates of fistula cure. Overall, quality-of-life scores improved postoperatively regardless of route of repair and use of interpositional flaps.
CONCLUSION
Our findings highlight the limited information available to guide evidence-based treatment of vesicovaginal fistula repair. Overall, high-quality evidence is lacking to provide guidelines; therefore, expert opinion remains the primary influence for fistula repair recommendations.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, CRD42021214948.
Topics: Female; Humans; Anti-Bacterial Agents; Fibrin Tissue Adhesive; Quality of Life; Urinary Bladder; Vesicovaginal Fistula
PubMed: 38033311
DOI: 10.1097/AOG.0000000000005468 -
BMJ Supportive & Palliative Care Jan 2024Methemoglobinemia, due to the oxidation of iron from ferrous to ferric form in the haemoglobin molecule, results in decreased oxygen delivery to the tissues....
Methemoglobinemia, due to the oxidation of iron from ferrous to ferric form in the haemoglobin molecule, results in decreased oxygen delivery to the tissues. Phenazopyridine, a commonly used medication for urinary symptoms, is a rare cause of methemoglobinemia. We report an elderly woman with advanced vaginal cancer, who developed methemoglobinemia following the use of phenazopyridine at a dose of 200 mg three times a day for 14 days. She presented with dyspnoea without cyanosis, oxygen saturation of 70%, methemoglobin concentration of 32.2% in arterial blood gas analysis and haemoglobin of 5 g/dL. This condition was identified and treated with methylene blue and oxygen support, which resulted in complete recovery in two days. Though rare, this highlights the importance of ascertaining reversible causes of symptoms, even in palliative care settings. Medications as an aetiology of symptoms should be considered even if they were used on a long-term basis.
PubMed: 38167589
DOI: 10.1136/spcare-2023-004692 -
Environmental Science and Pollution... Oct 2023Pharmaceutical wastewater treatment is an essential component of environmental protection and sustainable development. In this study, our aim was to investigate the...
Pharmaceutical wastewater treatment is an essential component of environmental protection and sustainable development. In this study, our aim was to investigate the morphology, characterization, and effectiveness of TiO/graphene composite nanofiber photocatalysts in the treatment of pharmaceutical wastewater containing three different pharmaceutical groups, such as an antibiotic (rifampin), painkiller (phenazopyridine), and immunosuppressant (azathioprine). Various parameters such as pH, salt concentration, and initial pharmaceutical compound concentration were optimized to achieve maximum degradation kinetics and efficiency. The optimum conditions were determined to be 1.5% graphene content, 30 ppm initial concentration of pharmaceutical compound, pH=5, and a 0.5 g/L photocatalyst dose. The presence of salt slightly decreased the degradation kinetics, but it did not significantly affect the performance of the TiO/graphene composite nanofibers photocatalyst. At optimum condition, TiO/1.5% graphene composite nanofibers degraded 50% of phenazopyridine, 86.89% of rifampin, and completely azathioprine. Comparing with phenazopyridine, N heteroatom-rich molecule of azathioprine and hydroxyl-rich molecule of rifampin lead to being susceptible to photocatalytic degradation. The reuse of the photocatalyst in multiple cycles showed consistent performance, indicating its potential for practical and economic applications.
Topics: Phenazopyridine; Nanofibers; Azathioprine; Graphite; Rifampin; Titanium; Pharmaceutical Preparations; Catalysis
PubMed: 37747607
DOI: 10.1007/s11356-023-29869-9 -
Gene Jul 2023Patients with chronic kidney disease (CKD) suffered from vascular calcification (VC), one major contributor for their increased mortality rate. Hedgehog (Hh) signaling...
BACKGROUND
Patients with chronic kidney disease (CKD) suffered from vascular calcification (VC), one major contributor for their increased mortality rate. Hedgehog (Hh) signaling plays a crucial role in physiological bone mineralization and is associated with several cardiovascular diseases. However, the molecular changes underlying VC is ill defined and it remains unclear whether Hh signaling intervention affects VC.
METHODS
We constructed human primary vascular smooth muscle cell (VSMC) calcification model and performed RNA sequencing. Alizarin red staining and calcium content assay were conducted to identify the occurrence of VC. Three different R packages were applied to determine differentially expressed genes (DEGs). Enrichment analysis and protein-protein interaction (PPI) network analysis were carried out to explore the biological roles of DEGs. qRT-PCR assay was then applied to validate the expression of key genes. By using Connectivity Map (CMAP) analysis, several small molecular drugs targeting these key genes were obtained, including SAG (Hedgehog signaling activator) and cyclopamine (CPN) (Hedgehog signaling inhibitor), which were subsequently used to treat VSMC.
RESULTS
Obvious Alizarin red staining and increased calcium content identified the occurrence of VC. By integrating results from three R packages, we totally obtained 166 DEGs (86 up-regulated and 80 down-regulated), which were significantly enriched in ossification, osteoblast differentiation, and Hh signaling. PPI network analysis identified 10 key genes and CMAP analysis predicted several small molecular drugs targeting these key genes including chlorphenamine, isoeugenol, CPN and phenazopyridine. Notably, our in vitro experiment showed that SAG markedly alleviated VSMC calcification, whereas CPN significantly exacerbated VC.
CONCLUSIONS
Our research provided deeper insight to the pathogenesis of VC and indicated that targeting Hh signaling pathway may represent a potential and effective therapy for VC.
Topics: Humans; Hedgehog Proteins; Calcium; Vascular Calcification; Signal Transduction; Myocytes, Smooth Muscle
PubMed: 37141952
DOI: 10.1016/j.gene.2023.147457 -
Clinical Pharmacology and Therapeutics Jun 2024Many drug labels contain precautions of use in G6PD-deficient patients due to hemolytic concerns, but much of this is based on scarce clinical, epidemiological, or...
Many drug labels contain precautions of use in G6PD-deficient patients due to hemolytic concerns, but much of this is based on scarce clinical, epidemiological, or structural data. In this real-world study, we aimed to examine if the administration of presumably risky medications for G6PD-deficient patients was followed by hemolysis. The study is based on data from Clalit Health Services database that provides inclusive health care for more than half of the Israeli population (~ 4.7 million). Within the database, we identified all G6PD-deficient patients by G6PD <6 U/g Hb. Within the G6PD-deficient cohort, we identified all hospitalizations with a discharge diagnosis of hemolysis (January 1, 2010 to December 31, 2022), validated the cases, and identified the culprit event. For the rest of the G6PD-deficient patients with no-hemolysis, we recorded filled prescriptions of medications listed as presumably risky. We identified 31,962 G6PD-deficient patients. Within the cohort, there were 71 cases of major hemolysis requiring hospitalization (0.2% of the cohort), of whom 51 (71.8%) had been caused by ingestion of fava beans, six (8.5%) were associated with an infection, and three (4.2%) suggested to be associated with medications (nitrofurantoin, phenazopyridine, and a "pain killer"). Within the 31,875 patients with no major hemolysis, nitrofurantoin has been prescribed safely to 1,366 G6PD-deficient males and females; hundreds/thousands of G6PD-deficient patients had been prescribed safely ciprofloxacin, glibenclamide, ofloxacin, phenazopyridine, sulfamethoxazole/cotrimoxazole, sulfasalazine, hydroxychloroquine, glimepiride, mesalazine, and sulfacetamide. In this real-world study, we are showing that a list of medications, suspected previously as carrying risks for hemolysis in G6PD-deficient patients, have been prescribed safely to G6PD-deficient patients, providing reassurance to patients, prescribers, and regulators.
PubMed: 38842030
DOI: 10.1002/cpt.3333 -
Urology Practice Jun 2024Office administration of intradetrusor onabotulinumtoxinA is commonly used to treat overactive bladder. For preprocedure analgesia, either 50 mL 2% intravesical...
INTRODUCTION
Office administration of intradetrusor onabotulinumtoxinA is commonly used to treat overactive bladder. For preprocedure analgesia, either 50 mL 2% intravesical lidocaine instillation for 20 to 30 minutes or 200 mg oral phenazopyridine can be used. Phenazopyridine is associated with shorter appointment times and is noninferior to lidocaine for pain control in this setting. We performed a cost analysis of phenazopyridine vs lidocaine for analgesia before office intradetrusor onabotulinumtoxinA injection for the treatment of idiopathic overactive bladder.
METHODS
A health care sector-perspective cost analysis was performed. The following assumptions were made: (1) similar efficacy of each medication in providing adequate analgesia, (2) similar physician ease of performing the procedure with either analgesic, and (3) similar patient satisfaction with either analgesic. Average cost of medications, adverse reactions, nursing tasks, and office visit time were found in publicly available data. Sensitivity analyses were performed using TreeAge Pro 2021, R1 software.
RESULTS
Phenazopyridine is less costly compared to lidocaine per visit for office intradetrusor onabotulinumtoxinA injection ($827 vs $925). A difference of $98 per procedure provides a total annual cost savings of over $24 million if all procedures are performed with phenazopyridine instead of lidocaine. Sensitivity analysis showed that phenazopyridine remained less costly under most circumstances, and threshold analysis provided exact circumstances under which phenazopyridine is no longer cost saving.
CONCLUSIONS
Phenazopyridine provides cost savings compared to lidocaine for analgesia before office intradetrusor onabotulinumtoxinA injection for the treatment of idiopathic overactive bladder. If adopted by providers nationwide, phenazopyridine may reduce health care spending and minimize office visit time while maintaining patient pain control and satisfaction.
PubMed: 38913587
DOI: 10.1097/UPJ.0000000000000628