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Background Current diagnoses of urinary tract infection (UTI) by standard urine culture (SUC) has significant limitations in sensitivity, especially for fastidious organisms, and the ability to identify organisms in polymicrobial infections. The significant rate of both SUC “negative” or “mixed flora/contamination” results in UTI cases and the high prevalence of asymptomatic bacteriuria indicate the need for an accurate diagnostic test to help identify true UTI cases. This study aimed to determine if infection-associated urinary biomarkers can differentiate definitive UTI cases from non-UTI controls. Methods Midstream clean-catch voided urine samples were collected from asymptomatic volunteers and symptomatic subjects ≥ 60 years old diagnosed with a UTI in a urology specialty setting. Microbial identification and density were assessed using a multiplex PCR/pooled antibiotic susceptibility test (M-PCR/P-AST) and SUC. Three biomarkers [neutrophil gelatinase-associated lipocalin (NGAL), and Interleukins 8 and 1β (IL-8, and IL-1β)] were also measured via enzyme-linked immunosorbent assay (ELISA). Definitive UTI cases were defined as symptomatic subjects with a UTI diagnosis and positive microorganism detection by SUC and M-PCR, while definitive non-UTI cases were defined as asymptomatic volunteers. Results We observed a strong positive correlation (R 2  > 0.90; p  < 0.0001) between microbial density and the biomarkers NGAL, IL-8, and IL-1β for symptomatic subjects. Biomarker consensus criteria of two or more positive biomarkers had sensitivity 84.0%, specificity 91.2%, positive predictive value 93.7%, negative predictive value 78.8%, accuracy 86.9%, positive likelihood ratio of 9.58, and negative likelihood ratio of 0.17 in differentiating definitive UTI from non-UTI cases, regardless of non-zero microbial density. NGAL, IL-8, and IL-1β showed a significant elevation in symptomatic cases with positive microbe identification compared to asymptomatic cases with or without microbe identification. Biomarker consensus exhibited high accuracy in distinguishing UTI from non-UTI cases. Conclusion We demonstrated that positive infection-associated urinary biomarkers NGAL, IL-8, and IL-1β, in symptomatic subjects with positive SUC and/or M-PCR results was associated with definitive UTI cases. A consensus criterion with ≥ 2 of the biomarkers meeting the positivity thresholds showed a good balance of sensitivity (84.0%), specificity (91.2%), and accuracy (86.9%). Therefore, this biomarker consensus is an excellent supportive diagnostic tool for resolving the presence of active UTI, particularly if SUC and M-PCR results disagree.

This study compared rates of empirical-therapy use and negative patient outcomes between complicated and recurrent urinary tract infection (r/cUTI) cases diagnosed with a multiplex polymerase chain reaction or pooled antibiotic susceptibility testing (M-PCR/P-AST) vs. standard urine culture (SUC). Subjects were 577 symptomatic adults (n = 207 males and n = 370 females) presenting to urology/urogynecology clinics between 03/30/2022 and 05/24/2023. Treatment and outcomes were recorded by the clinician and patient surveys. The M-PCR/P-AST (n = 252) and SUC (n = 146) arms were compared after patient matching for confounding factors. The chi-square and Fisher’s exact tests were used to analyze demographics and clinical outcomes between study arms. Reduced empirical-treatment use (28.7% vs. 66.7%), lower composite negative events (34.5% vs. 46.6%, p = 0.018), and fewer individual negative outcomes of UTI-related medical provider visits and UTI-related visits for hospitalization/an urgent care center/an emergency room (p < 0.05) were observed in the M-PCR/P-AST arm compared with the SUC arm. A reduction in UTI symptom recurrence in patients ≥ 60 years old was observed in the M-PCR/P-AST arm (p < 0.05). Study results indicate that use of the M-PCR/P-AST test reduces empirical antibiotic treatment and negative patient outcomes in r/cUTI cases.

Background: Here, we validate a unique and rapid susceptibility assay, Pooled Antibiotic Susceptibility Testing (P-AST), used for complicated, persistent, and recurrent urinary tract infections (UTIs), following Clinical and Laboratory Standards Institute (CLSI) protocols and performance metrics. Methods: P-AST™ was validated against the standard disk diffusion method with discrepancy resolution by the broth microdilution reference method. Performance was evaluated for five groups of non-fastidious uropathogenic organisms (Enterobacterales, Enterococci, Staphylococci, Pseudomonas aeruginosa, and Acinetobacter species) for up to 20 antibiotics, as clinically relevant per group. Fresh (144 monomicrobial and 49 polymicrobial) and frozen (78 monomicrobial and 7 polymicrobial) clinical urine specimens, as well as contrived specimens from pre-characterized frozen “challenge” isolates (52 monomicrobial and 37 polymicrobial), were included. Results: P-AST met CLSI target performance criteria of ≥90.0% categorical agreement, <3.0% very major error, <3.0% major error, minor error ≤ 10.0%, or within laboratory standards, and precision > 95.0% across all analysis groups. Across all monomicrobial analyses, there were no very major errors (VMEs), and two major errors (MEs). Across all polymicrobial analyses, there were three VMEs and two MEs. No organism–antibiotic pair analysis had more than a single VME or ME. Conclusions: P-AST, a component of the Guidance® UTI assay, demonstrates acceptable performance within the thresholds established by CLSI when compared against standard and reference methods for antibiotic susceptibility testing. Appropriate performance was established in both monomicrobial and polymicrobial specimens for five CLSI-defined groups of uropathogenic bacteria, against up to 20 antibiotics as clinically relevant to each organism group.

Background Trimethoprim-sulfamethoxazole (TMP-SMX) is the drug of choice for anti- Pneumocystis jirovecii pneumonia (PcP) prophylaxis in kidney transplant recipients (KTR). Post-transplant management balances preventing PcP with managing TMP-SMX-related adverse effects. TMP-SMX dose reduction addresses adverse effects but its implications to incident PcP are unclear. Methods We performed a retrospective review of all patients transplanted between 2011 and 2015 prescribed daily single strength TMP-SMX for twelve months post-transplantation as PcP prophylaxis. Actual TMP-SMX dose and duration, adverse effects, number of dose reductions and reasons, and PcP events were captured. Multivariate logistic regression analyses for risk factors associated with dose reduction were performed. Results Of 438 KTR, 233 (53%) maintained daily TMP-SMX and 205 (47%) sustained ≥1 dose reduction, with the point prevalence of a reduced dose regimen being between 18 and 25%. Median duration for daily TMP-SMX was 8.45/12 months, contributing 4137 patient-months daily TMP-SMX and 1110 patient-months with a reduced dose. PcP did not occur in any patients. There were 84 documented dose reductions for hyperkalemia and 102 for leukopenia, with 12 and 7 patients requiring TMP-SMX cessation. In multivariate analysis, a living donor transplant protected against hyperkalemia (Odds Ratio 0.46, 95% CI 0.26–0.83, p  < 0.01) while acute rejection risked leukopenia (Odds Ratio 3.31, 95% CI 1.39–7.90, p  = 0.006). Conclusions TMP-SMX dose reduction is frequent in the first post-transplant year but PcP does not occur. To limit the need for TMP-SMX dose reduction due to adverse effects, a clinical trial comparing daily to thrice weekly single strength TMP-SMX in de-novo KTR is justified.

Background Immunoglobulin A nephropathy (IgAN) is one of the most common forms of primary glomerulonephritis (GN) worldwide. While specific treatment differs regionally, treatment usually focuses on background therapy, with short-term (≤ 6 months) corticosteroids recommended as an add-on treatment for patients at high risk of progressive chronic kidney disease. Although corticosteroids can help to manage IgAN, treatment with corticosteroids may lead to undesirable adverse outcomes. Objective To highlight corticosteroid treatment burden in patients with IgAN globally. Methods Embase, MEDLINE, and Cochrane CENTRAL were searched for articles published in any language from January 1, 2013 to August 24, 2023. Eligible studies reported ≥ 1 outcome related to the clinical, humanistic, or economic burden of corticosteroids in patients with IgAN. Articles were independently screened by 2 reviewers. Data extraction and quality assessment were completed by 1 researcher and validated by a second. Results are reported among the number of studies with data on each outcome. Results Of 1,024 records screened, 64 studies were included. Of 37 studies reporting treatment duration, 68% found that corticosteroids were used long-term (range: 8–24 months). In studies reporting data for long-term use (> 6 months), there were more overall AEs and serious AEs with corticosteroids than with comparator treatments (e.g., background therapy alone, tonsillectomy, placebo). Rates of metabolic AEs, Cushing’s syndrome, edema and sleep disorders were also higher with long-term corticosteroids than with comparator treatments; however, most studies did not report the statistical significance of these results. Infection rates were similar between corticosteroids and comparator treatments. Conclusions Current guidelines recommend short-term corticosteroid treatment for patients at high risk of progression but long-term use appears to be widespread. Corticosteroids may lead to adverse outcomes and should therefore be reserved only for IgAN patients most at risk of rapid progression to end-stage kidney disease and for limited duration. Novel corticosteroid-sparing therapies are necessary to supplement the current treatment landscape.

Background/Objectives: While new methods for measuring antimicrobial susceptibility have been associated with improved patient outcomes, they should also be validated using standard protocols for error rates and other test metrics. The objective of this study was to validate a novel susceptibility assay for complicated and recurrent urinary tract infections (UTIs): pooled antibiotic susceptibility testing (P-AST). This assay was compared to broth microdilution (BMD) and disk diffusion (DD), following Clinical and Laboratory Standards Institute (CLSI) guidelines for assessment of error rates and agreement. Methods: This study analyzed consecutive fresh clinical urine specimens submitted for UTI diagnostic testing. Upon receipt, the urine samples were subjected in parallel to standard urine culture and multiplex polymerase chain reaction (M-PCR) for microbial identification and quantification. Specimens with the same monomicrobial non-fastidious bacteria detected by both M-PCR and standard urine culture (SUC) underwent standard antibiotic susceptibility testing (AST) and P-AST antibiotic susceptibility testing. Analysis was also undertaken to assess the presence of heteroresistance for specimens with P-AST-resistant and BMD/DD consensus-susceptible results. Results: The performance measures without correction for heteroresistance showed essential agreement (EA%) of ≥90%, very major errors (VMEs) of <1.5%, and major errors (MEs) of <3.0% for P-AST, all meeting the threshold guidelines established by CLSI for AST. The categorical agreement (CA%) also met acceptable criteria (>88%), as the majority of the errors were minor (mEs) with essential agreement. The very major and major error rates for P-AST decreased to <1.0% when heteroresistance was accounted for. Conclusions: The P-AST assay methodology is validated within acceptable parameters when compared to broth microdilution and disk diffusion using CLSI criteria.

There are ancient texts and modern studies alluding to the therapeutic benefits obtained from listening to music. Studies have shown that chanting \"OM\" has a relaxing effect by causing parasympathetic dominance, limbic deactivation, and decreasing the brain's dopamine levels. This research aims to study the effect of listening to OM chanting on the cardiovascular system and heart rate variability and its possible use as a stress buster among medical students. Fifty medical undergraduates were selected for the study. After a 20-minute relaxation, a lead 2 electrocardiogram (EKG) was recorded for 10 minutes. Their blood pressure (BP) and heart rate were measured. The subjects were then made to listen to OM chanting for 20 minutes, immediately after which their BP and heart rate were measured. This was followed by another 10-minute lead 2 EKG. The EKGs recorded were then used to calculate the standard deviation in N-N interval (SDNN), total power, high-frequency power, and low-frequency power. The study reported a significant decrease in blood pressure and heart rate and a significant increase in SDNN and total power. There was also an insignificant increase in low frequency and an insignificant decrease in high frequency.  This study provides insight into the importance of spiritual music therapy in the maintenance of mental as well as cardiovascular health among medical students.

The literature lacks consensus on the minimum microbial density required for diagnosing urinary tract infections (UTIs). This study categorized the microbial densities of urine specimens from symptomatic UTI patients aged ≥ 60 years and correlated them with detected levels of the immune response biomarkers neutrophil gelatinase-associated lipocalin (NGAL), interleukin-8 (IL-8), and interleukin-1-beta (IL-1β). The objective was to identify the microbial densities associated with significant elevation of these biomarkers in order to determine an optimal threshold for diagnosing symptomatic UTIs. Biobanked midstream voided urine samples were analyzed for microbial identification and quantification using standard urine culture (SUC) and multiplex-polymerase chain reaction (M-PCR) testing, while NGAL, IL-8, and IL-1β levels were measured via enzyme-linked immunosorbent assay (ELISA). NGAL, IL-8, and IL-1β levels were all significantly elevated at microbial densities ≥ 10,000 cells/mL when measured via M-PCR (p < 0.0069) or equivalent colony-forming units (CFUs)/mL via SUC (p < 0.0104) compared to samples with no detectable microbes. With both PCR and SUC, a consensus of two or more elevated biomarkers correlated well with microbial densities > 10,000 cells/mL or CFU/mL, respectively. The association between ≥10,000 cells and CFU per mL with elevated biomarkers in symptomatic patients suggests that this lower threshold may be more suitable than 100,000 CFU/mL for diagnosing UTIs.

Background/Objectives: Urinary tract infections (UTIs) pose an increasing risk of antimicrobial resistance, and novel diagnostic tests have been developed to address the limitations of standard urine culture in these cases. It is important that these novel tests be validated for agreement and error rates against the standard antibiotic susceptibility testing (AST) methods. Methods: Polymicrobial (≥two non-fastidious microorganisms) consecutive clinical urine specimens submitted for UTI diagnostic testing were included in this analysis. Specimens were tested with Pooled Antibiotic Susceptibility Testing (P-AST) and with broth microdilution/disk diffusion (BMD/DD) in parallel. Performance characteristics, such as essential agreement (EA%), very major errors (VMEs), and major errors (MEs), were assessed using Clinical and Laboratory Standards Institute (CLSI) standards. Specimens with P-AST-resistant and BMD/DD consensus-sensitive results were assessed for heteroresistance. Real-world clinical sample data were used to assess associations between increasing organism counts and average “sensitive” antibiotic count per sample. Results: The essential agreement between P-AST and standard isolate AST was ≥90%, VMEs were <2.0%, and MEs were <3.0%, meeting the CLSI guidelines for AST verification and validation studies. When heteroresistance was accounted for, overall VMEs and MEs were both <1.5%. The presence of additional non-fastidious organisms dropped the number of average “sensitive” antibiotics from 9.8 with one organism to 2.5 with five or more organisms. The presence of fastidious organisms did not have any meaningful impact. Conclusions: P-AST, a component of the Guidance® UTI assay (Pathnostics, Irvine, CA, USA), performed within CLSI standards for AST in polymicrobial UTI diagnostic urine specimens.