Effect of methenamine hippurate shortage on antibiotic prescribing for urinary tract infections in Norway-an interrupted time series analysis.

BACKGROUND: Despite a lack of conclusive evidence of effect, methenamine hippurate is widely prescribed as preventive treatment for recurrent urinary tract infections (UTIs) in Norway. A national discontinuation of methenamine hippurate treatment due to a 4-month drug shortage in 2019 presented an opportunity to evaluate its preventive effect on UTIs among regular users. OBJECTIVE: To estimate the impact of the methenamine hippurate drug shortage on prescription frequency of UTI antibiotics. METHODS: Data from The Norwegian Prescription Database was analysed using an interrupted time series design. The time series consisted of 56 time periods of 14 days. The model included two naturally occurring interruptions: (i) the methenamine hippurate drug shortage, and (ii) reintroduction of the drug. The study population were 18 345 women ≥50 years receiving ≥2 prescriptions of methenamine hippurate in the study period before the shortage. Main outcome measure was number of prescriptions of UTI antibiotics per 1000 methenamine hippurate users. Prescription rates of antibiotics for respiratory tract infections were analysed to assess external events affecting antibiotic prescribing patterns. RESULTS: We found a significant increase of 2.41 prescriptions per 1000 methenamine hippurate users per 14-day period during the drug shortage (95%CI 1.39, 3.43, P < 0.001), followed by a significant reduction of -2.64 prescriptions after reintroduction (95%CI -3.66, -1.63, P < 0.001). CONCLUSIONS: During the methenamine hippurate drug shortage, we found a significant increase in prescribing trend for UTI antibiotics followed by a significant decrease in prescribing trend after reintroduction. This change in trend seems to reflect a preventive effect of the drug on recurrent UTIs.

Synthesis and Application of Carbon Quantum Dots Derived from Carbon Black in Bioimaging.

Carbon quantum dots (CQDs) are a new type of fluorescent QDs that consists mainly of carbon atoms. In this research, CQDs were synthesized through harsh oxidizing conditions applied on carbon black and subsequent N-doping using hexamethylenetetramine (Hexamine) and polyethyleneimine (PEI). The synthesized CQDs were characterized using FTIR, AFM, UV-Visible spectroscopy, photoluminescence (PL) spectroscopy, and fluorescence imaging respectively. The AFM images showed that the dots are in the range of 2-8 nm. N-doping of the CQDs increased the PL intensity. The PL enhancement for the CQDs that were N-doped with PEI was higher compared to those N-doped with hexamine. The shift in PL by changing the excitation wavelength has been attributed to the nano-size of the CQDs, functional groups, defect traps, and quantum confinement effect. The in vitro fluorescence imaging revealed that N-doped CQDs can internalize into the cells and be used for fluorescent cell imaging.

Use of Methenamine for Urinary Tract Infection Prophylaxis: Systematic Review of Recent Evidence.

INTRODUCTION AND HYPOTHESIS: Antibiotic resistance is an unavoidable consequence of antibiotic use and growing rates of resistance are an urgent issue. Methenamine is a non-antibiotic alternative used for urinary tract infection (UTI) prophylaxis. The objective of this review is to evaluate recently published literature regarding the efficacy and safety of methenamine for UTI prophylaxis. METHODS: PubMed, Embase, and CENTRAL databases were queried in March 2023 using the following search terms: urinary tract infection, cystitis, bacteriuria, or dysuria, and methenamine. Studies prior to 2012 were excluded from this review to focus on appraisal of the most recent evidence. Prospective and controlled retrospective trials were included for review. RESULTS: A total of seven studies (three prospective and four retrospective) met the inclusion criteria for review. Two of the 3 prospective studies demonstrated no or non-inferior differences in clinical efficacy to prevent recurrent UTIs between methenamine and antibiotic prophylaxis and the third showed decreased rates of UTI with methenamine use in patients with short-term indwelling catheters compared with cranberry alone. The retrospective studies consistently supported the efficacy and safety of methenamine for UTI prophylaxis in a variety of populations and clinical settings. Adverse effects reported with methenamine were similar to comparators and included nausea, abdominal pain, and headache. CONCLUSIONS: The use of methenamine for UTI prophylaxis was shown to be effective in a variety of settings without an increased risk of adverse effects compared with prophylactic antibiotics. Larger blinded clinical trials are needed to further define the role of methenamine in UTI prophylaxis.

Morphological and etiological analyses of C3 and non-C3 glomerulonephritis in primary membranoproliferative glomerulonephritis using periodic acid-methenamine silver stain electron microscopy: a retrospective multicentered study.

This study elucidated the etiology of C3 glomerulonephritis (C3GN) and non-C3GN with primary membranoproliferative glomerulonephritis (MPGN) using transmission electron microscopy (TEM) and periodic acid-methenamine silver stain (PAM-EM). Thirty-one primary MPGN cases were analyzed by TEM and PAM-EM to distinguish among MPGN I, MPGN II, MPGN III Burkholder subtype (MPGN IIIB), and Anders and Strife subtype (MPGN IIIA/S). Each case was also classified into C3GN or non-C3GN according to the standard C3GN definition using immunostaining. Four cases of MPGN II met C3 glomerulopathy; whereas, four cases of MPGN IIIB did not meet C3 glomerulopathy. Seven of 11 cases (64%) of MPGN I without GBM disruption and 7 of 12 cases (58%) of MPGN IIIA/S with GBM disruption met the non-C3GN criteria with significant immunoglobulins' deposition. Regardless of the C3GN or non-C3GN diagnosis, the deposits in primary MPGN I and MPGN IIIA/S exhibited ill-defined, amorphous, and foggy characteristics similar to those found in postinfectious GN but were different from immune complex (IC) deposits seen in MPGN IIIB. Not only C3GN but also non-C3GN was due to mechanisms other than IC deposition as found in postinfectious GN. Consequently, GBM disruption of MPGN IIIA/S was not due to IC deposition.

Standardization of Grocott's methenamine (hexamine) silver method for glycogen demonstration in liver tissue.

Demonstration of glycogen can be done in different lesions and is considered diagnostically significant, mainly in some tumors. Glycogen staining is affected by the type of fixative, the temperature of fixation, and the staining technique.Grocott's methenamine (hexamine) silver technique quality was assessed after four different types of fixatives at two different temperatures [Bouin's solution, 10% neutral buffered formalin (NBF), 80% alcohol, and Rossman's solution at room temperature (RT) and 4 °C, for 24 h]. These variables were studied to optimize this technique for glycogen demonstration. Archived paraffin blocks were used in this study. They were prepared from one rabbit's liver, and 32 paraffin sections were prepared and stained with Grocott's methenamine (hexamine) silver technique. Eighty percent alcohol provided the highest staining quality scores at both RT and 4 °C in comparison with the other fixatives. We concluded that 80% alcohol at 4 °C seems to be the fixative of choice for glycogen with the Grocott's methenamine (hexamine) silver technique at the level of this study.

The resurgence of methenamine hippurate in the prevention of recurrent UTIs in women- a systematic review.

PURPOSE OF REVIEW: Recurrent urinary tract infections (rUTIs) in women are prevalent and difficult to manage. The rise of antimicrobial resistance makes it prudent to re-investigate the role of nonantimicrobial agents in the prevention of RUTIs. We wanted to evaluate randomised controlled trials (RCTs) that employed methenamine hippurate as a therapy or prophylactic in adult women with rUTIs. RECENT FINDINGS: Relevant databases were searched for RCTs using Cochrane methodology and reporting items for systematic reviews and meta-analyses (PRISMA) checklist, comparing the efficacy of methenamine hippurate to either an antibiotic or a placebo for the prophylaxis of rUTI in women.Six trials involving 322 patients taking methenamine and 419 patients receiving antibiotics in total were evaluated. The duration of the trials ranged from 12-24 months. Studies reported that methenamine was effective in extending the mean period between symptomatic episodes of urinary tract infections (UTIs), keeping the patient symptom- and infection-free, and reducing the number of UTI episodes. The newer studies reported that methenamine reduced the incidence rates of recurrent UTIs and was not inferior to the antibiotic in this regard. SUMMARY: The outcomes of methenamine hippurate were found to be at par with the antibiotic prophylaxis. It might serve as a suitable alternative nonantibiotic prophylaxis for females with rUTIs.

Evidence-based review of nonantibiotic urinary tract infection prevention strategies for women: a patient-centered approach.

PURPOSE OF REVIEW: There is a growing interest in nonantibiotic prevention strategies for recurrent urinary tract infections (rUTIs). Our objective is to provide a focused, pragmatic review of the latest evidence. RECENT FINDINGS: Vaginal estrogen is well tolerated and effective for preventing rUTI in postmenopausal women. Cranberry supplements at sufficient doses are effective in preventing uncomplicated rUTI. Methenamine, d -mannose, and increased hydration all have evidence to support their use, although the evidence is of somewhat variable quality. SUMMARY: There is sufficient evidence to recommend vaginal estrogen and cranberry as first-line rUTI prevention strategies, particularly in postmenopausal women. Prevention strategies can be used in series or in tandem, based on patient preference and tolerance for side effects, to create effective nonantibiotic rUTI prevention strategies.

Effective interactions and phase behavior of protein solutions in the presence of hexamine cobalt(III) chloride.

It is well established that deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) exhibit a reentrant condensation (RC) phase behavior in the presence of the trivalent hexamine cobalt(III) cations (Hac) which can be important for their packing and folding. A similar behavior can be observed for negatively charged globular proteins in the presence of trivalent metal cations, such as Y3+ or La3+. This phase behavior is mainly driven by charge inversion upon an increasing salt concentration for a fixed protein concentration (cp). However, as Hac exhibits structural differences compared to other multivalent metal cations, with six ammonia ligands (NH3) covalently bonded to the central cobalt atom, it is not clear that Hac can induce a similar phase behavior for proteins. In this work, we systematically investigate whether negatively charged globular proteins ß-lactoglobulin (BLG), bovine serum albumin (BSA), human serum albumin (HSA) and ovalbumin (OVA) feature Hac-induced RC. Effective protein-protein interactions were investigated by small-angle X-ray scattering. The reduced second virial coefficient (B2/B2HS) was obtained as a function of salt concentration. The virial coefficient analysis performed confirms the reentrant interaction (RI) behavior for BLG without actually inducing RC, given the insufficient strengths of the interactions for the latter to occur. In contrast, the strength of attraction for BSA, HSA and OVA are too weak to show RC. Model free analysis of the inverse intensity [Formula: see text] also supports this finding. Looking at different q-range by employing static (SLS) and dynamic light scattering experiments, the presence of RI behavior can be confirmed. The results are further discussed in view of metal cation binding sites in nucleic acids (DNA and RNA), where Hac induced RC phase behavior.

Efficacy of methenamine with methylthioninium in the treatment of dysuria: a randomized clinical study.

INTRODUCTION AND HYPOTHESIS: Dysuria is a common symptom present in several urological and gynecological conditions. Management relies on the underlying disease but may require additional symptomatic treatment. This study evaluated the combination of methenamine 250 mg and methylthioninium chloride 20 mg in the treatment of dysuria versus phenazopyridine. METHODS: This was a multicenter, single-blind, randomized, superiority clinical trial, including individuals over 18 with dysuria and a score ≥ 5 points on the pre-treatment categorical scale for pain. The primary outcome was the proportion of participants presenting excellent clinical response within 24 h after treatment. Improvement up to 72 h, time to reach improvement, sustained healing, investigators' opinion, and safety were also evaluated. RESULTS: Three hundred and fifteen participants were evaluated. Demographic characteristics and symptoms of dysuria were comparable between groups at baseline. The difference in the excellent response rate between treatments within 24 h was 12.7% (95% CI 6.16, 19.21) for pain, 9.4% (95% CI 3.32, 15.39) for burning, and 12.7% (95% CI 6.37, 18.99) for burning on urination, all in favor of the test drug, which was also superior from 36 to 48 h. Treatments were similar concerning time to reach the absence of symptoms and in the percentage of participants with sustained healing after 72 h. CONCLUSIONS: The association of methenamine with methylthioninium is superior to phenazopyridine in the treatment of dysuria.

Anthracite based activated carbon impregnated with HMTA as an effectiveness adsorbent could significantly uptake gasoline vapors.

In this study, we synthesized and employed the amine impregnated activated carbon as an efficacious adsorbent for uptaking gasoline vapor. For this regard, anthracite as activated carbon source and hexamethylenetetramine (HMTA) as amine were selected and utilized. Physiochemical characterization of made sorbents were evaluated and investigated using SEM, FESEM, BET, FTIR, XRD, zeta potential, and elemental analysis. The synthesized sorbents provided an excellent textural features as compared with the literature and other activated carbon based sorbents and impregnated with amine. Our findings also suggested that in addition to high surface area (up to 2150 m2 / g), the micro- meso pores created (Vmeso / V micro = 0.79 Cm 3 / g) surface chemistry may significantly affect the gasoline sorption capacity, which here the role of mesoporous is further highlighted. V meso for amine impregnated sample and free activated carbon was 0.89 and 0.31 Cm 3 / g, respectively. According to the results, the prepared sorbents have a potential capability in uptaking gasoline vapor and with line this, we report a high sorption capacity of 572.56 mg / g. After, four cycles used the sorbent had a high durability and about 99.11% of the initial uptake was maintained. Taking together the synthesized adsorbents as an activated carbon provided an excellent and unique features and enhanced gasoline uptake, therefore its applicability in uptaking gasoline vapor can be substantially considered.

Synthesis and Behavior of Hexamethylenetetramine-Based Ionic Liquids as an Active Ingredient in Latent Curing Formulations with Ethylene Glycol for DGEBA.

The paper presents the preparation of new ionic liquids based on hexamethylenetetramine with bis(trifluoromethanesulfonyl)imide and dicyanamide anion, which were characterized in detail in terms of their purity (Ion Chromatography) and thermal properties (Differential Scanning Calorimetry), as well as stability. The obtained substances were used to develop curing systems with ethylene glycol, which were successfully tested for their application with bisphenol A diglycidyl ether molecule. In addition, the curing process and its relationship to the structure of the ionic liquid are characterized in detail. The research showed that hexamethylenetetramine-based new ionic liquids can be successfully designed using well-known and simple synthetic methods-the Delepine reaction. Moreover, attention was paid to their stability, related limitations, and the application of hexamethylenetetramine-based ionic liquids in epoxy-curing systems.

The management of recurrent urinary tract infections within a nurse-led urology team.

The aim of this article is to share experience and learning of managing recurrent urinary tract infections (UTIs) within a specialist urology nurse-led team based at a district general hospital. It looks at current practice and supporting evidence for how to manage and treat recurrent UTIs in both male and female patients. Two case studies are presented to illustrate the management strategies and outcomes, demonstrating a planned approach that informs the design of a local management guideline to organise patients' care.

Methenamine hippurate compared with trimethoprim for the prevention of recurrent urinary tract infections: a randomized clinical trial.

INTRODUCTION AND HYPOTHESIS: The objective was to find an alternative treatment to a low-dose antibiotic for the prevention of recurrent urinary tract infections (UTI) and to evaluate the difference in rates of reinfection within 1 year when treated with methenamine hippurate for prophylaxis compared with trimethoprim. METHODS: We present a non-blinded randomized trial comparing methenamine hippurate with trimethoprim for the prevention of recurrent UTI at 12 months after starting treatment. Women over 18 who had at least two culture-positive UTI in the prior 6 months or three in the prior year were included. Ninety-two patients met enrollment criteria and were randomized to receive daily prophylaxis with methenamine hippurate or trimethoprim for a minimum of 6 months. Both intent-to-treat and per-protocol analyses if patients received the alternative drug after randomization were analyzed using Student's t test, Mann-Whitney U test, Kaplan-Meier curves, log-rank test, and a logistic and multivariate regression model. The primary outcome of this study was culture-proven UTI recurrence by 12 months after initiating prophylaxis. RESULTS: In the intent-to-treat analysis, we found no difference between groups in recurrent UTI, with a 65% (28 out of 43) recurrence in the trimethoprim group versus 65% (28 out of 43) in the methenamine hippurate group (p = 1.00). In the per-protocol analysis, 65% (26 out of 40) versus 65% (30 out of 46) of patients had UTI recurrences in the trimethoprim group versus the methenamine hippurate group (p = 0.98). CONCLUSIONS: Methenamine hippurate may be an alternative for the prevention of recurrent UTI, with similar rates of recurrence and adverse effects to trimethoprim.

Leishmania (L.) infantum BH401 strain induces classic renal lesions in dogs: Histological and confocal microscopy study.

Extracellular matrix (ECM) alterations in visceral leishmaniasis are related mainly to collagen deposition (fibropoiesis). In canine visceral leishmaniasis (CVL), an intense fibrosis associated to chronic inflammation in organs such as kidneys is described. However, renal fibropoiesis has not been described in natural or experimental infections with L. (L.) infantum. We aimed to characterize renal nephropathies by histology and confocal microscopy comparing renal lesions in dogs naturally and experimentally infected with L. (L.) infantum. Sixty-two mixed-breed symptomatic dogs naturally infected with L. (L.) infantum, sixteen beagles experimentally infected with two strains of L. infantum (eleven dogs with the BH400 strain and five dogs with the BH401 strain), and five uninfected beagles (controls) were used. Samples were stained with hematoxylin & eosin for routine histology. Congo red was used to visualize amyloid protein deposits, periodic acid-Schiff to identify glomerular basal membrane anomalies, Masson's trichrome for collagen deposits, and Jones' methenamine silver to reveal membranous glomerulonephropathy. Immunohistochemistry was used to identify Leishmania amastigotes, and confocal microscopy was used for macrophage characterization (L1/calprotectin and CD163 antigen receptors). The most common lesions were chronic glomerular and interstitial nephritis, which was found in all naturally infected dogs and dogs experimentally infected with L. infantum strain BH401 but not with the BH400 strain. Glomeruloesclerosis was the main lesion presented in all BH401 group. Morphometric analysis revealed positive correlation of renal glomeruli tufts with cellular expression of L1/calprotectin and CD163 antigens. Leishmania infantum strain BH401 shows pathogenicity that may be sufficient to induce classic chronic visceral renal leishmaniasis.

Preventive effect of methenamine in women with recurrent urinary tract infections - a case-control study.

BACKGROUND: Urinary tract infection (UTI) is the most common bacterial infection in women. In Norwegian general practice, methenamine has been prescribed for many years as long-term prevention and accounted for 20% of the total antibiotic prescribing in 2015, as measured in defined daily dosages (DDDs). The efficacy of methenamine is unknown. If shown to be effective, this drug may become an important preventive against UTI. OBJECTIVE: To examine whether methenamine is preventive against recurrent UTI in women. DESIGN: Data for all antibiotics used for UTIs dispensed from all pharmacies from 2005 to 2015 were collected from the Norwegian prescription database (NorPD). SUBJECTS: Women aged ≥ 40 years with recurrent UTI, defined as ≥3 courses of UTI antibiotic/year, were included. MAIN OUTCOME MEASURES: Patients using methenamine (cases) and those not using methenamine (controls) were compared. The numbers of UTI prescriptions during the 2 years before and after inclusion were analysed. Results: The yearly prevalence for recurrent UTI was 2.4% in women ≥ 40 years. The change in antibiotic use from 2 years before to 2 years after inclusion in the study differed significantly between groups: 44.6 and 34.9% reductions in the number of antibiotic prescriptions for UTI in the methenamine and control groups, respectively. The decrease in UTI antibiotic prescriptions (58.9%) was greater in patients with a higher consumption of antibiotics before starting methenamine. CONCLUSIONS: Methenamine seems to be effective against recurrent UTI over the time span studied. The effect seems to be greater in patients with the highest number of recurrent UTIs. Key pointsMethenamine has been used for many years for prevention of recurrent UTI, but no studies have demonstrated a significant preventive effect of long time use.This study shows that methenamine seems to be effective for prevention in patients having recurrent UTI over 2 years or more.The effect seems to be larger in patients with a high number of UTIs over 2 years.

Formation of Ultimate Thin 2D Crystal of Pt in the Presence of Hexamethylenetetramine.

Platinum naturally crystalizes into a three-dimensional crystal due to its highly symmetrical fcc lattice, with a metallic bond which is non-directional and highly isotropic. This inherently means ultimately that 2D crystals of a few atoms thick growth are hardly available in this material. Here, we discovered that a combinative effect of formic acid reductant and hexamethylenetetramine surfactant during the reduction of their metal ions precursor can realize an ultimate thin 2D crystal growth in platinum. High-resolution transmission electron microscopy and filed-emission electron microscopy analysis have also discovered that the 2D crystal of Pt has 111 facets with a lateral dimension that can be up to more than 5 µm × 2 µm. The thickness of the 2D crystal of Pt is 1.55 nm. A mechanism for obtaining ultimate thin 2D crystal of Pt using the present approach is proposed.

3DG Functionalized Magnetic Solid Phase Extraction Materials for the Efficient Enrichment of Hexamethylenetetramine in Vermicelli.

Solid phase extraction (SPE) is regarded as the most effective purification method for complex matrix samples owing to its simplicity of operator, time-saving, high accuracy, and environmental friendliness. SPE technology is still affected by the high cost of commercial SPE columns and poor adsorption selectivity. Hence, the development of low-cost and highly selective adsorbents is quite challenging and demanding in SPE. In this study, a novel 3DG functionalized magnetic solid phase extraction materials was prepared based on "thiol-ene" click chemistry. The structure, morphology, thermal stability, and magnetic properties of the magnetic composites were studied by Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), thermogravimetric analysis (TGA), and vibrating sample magnetometer (VSM). Then the adsorption performance of composite was determined by static adsorption experiments, which showed fast binding kinetics (100 min) and good adsorption performance (Qe = 65.34 mg/g). Moreover, these magnetic nanoparticles were used as adsorbents for magnetic solid phase extraction (MSPE) and coupled with high-performance liquid chromatography (HPLC) for separation and detection of illegally added hexamethylenetetramine in vermicelli. As for practical application, the recoveries for the spiked samples in the concentration range of 8-40 µg/g were between 83.24-92.69%, and the RSD was between 0.20-2.07%.

Effectiveness of Methenamine for UTI Prevention in Older Adults.

Background: Methenamine is a drug used for the prevention of lower urinary tract infections (UTIs). However, efficacy has not been established in older adults or patients with varying degrees of kidney function. Objective: To evaluate the effectiveness of methenamine for the prevention of UTI in adults 60 years and older. Methods: This was a retrospective, pre-post, observational study. The study included primary care patients 60 years and older who were taking methenamine between January 1, 2015, and September 30, 2018. The primary outcome was the time to first UTI after methenamine initiation compared with the average time between UTIs in the 12 months prior to methenamine initiation. Results: Of 434 patients reviewed, 150 met inclusion criteria. The average time to UTI was 3.3 months prior to methenamine initiation compared with 5.5 months after methenamine initiation (P = 0.0004). There were 33 patients (22%) who did not have a UTI after methenamine initiation. Also, 14 patients (9.3%) had a calculated CrCl <30 mL/min at baseline. The average time to UTI in these patients was 3.3 months prior to methenamine initiation compared with 12.7 months after initiation (P < 0.0001). Conclusion and Relevance: Methenamine use was associated with a longer time to UTI in older adults with varying degrees of kidney function. The effectiveness of methenamine appeared to be similar regardless of kidney function, which is new evidence. Because of a lack of acquired resistance, methenamine may be an effective option for UTI prophylaxis in older adults.

PAS and GMS utility in dermatopathology: Review of the current medical literature.

The American Society of Dermatopathology has established an Appropriate Use Criteria (AUC) Committee with the intention of establishing evidence-based recommendations regarding the appropriateness of various ancillary tests commonly utilized by dermatopathologists. Periodic acid Schiff (PAS) and Grocott (or Gomori) methenamine silver (GMS) stains represent some of the most commonly employed ancillary tests in dermatopathology. The utility of these tests was targeted for evaluation by the AUC. This literature review represents a comprehensive evaluation of available evidence for the utility of PAS and/or GMS staining of skin and nail biopsies. In concert with expert opinion, these data will be incorporated into future recommendations by the AUC for PAS and GMS staining in routine dermatopathology practice.