Design and protocol for a cluster randomised trial of enhanced diagnostics for tuberculosis screening among people living with HIV in hospital in Malawi (CASTLE study)

Background People living with HIV (PLHIV) have a high risk of death if hospitalised in low-income countries. Tuberculosis has long been the leading cause of admission and death, in part due to suboptimal diagnostics. Two promising new diagnostic tools are digital chest Xray with computer-aided diagnosis (DCXR-CAD) and urine testing with Fujifilm SILVAMP LAM (FujiLAM). Neither test has been rigorously evaluated among inpatients. Test characteristics may be complementary, with FujiLAM especially sensitive for disseminated tuberculosis and DCXR-CAD especially sensitive for pulmonary tuberculosis, making combined interventions of interest. Design and methods An exploratory unblinded, single site, two-arm cluster randomised controlled trial, with day of admission as the unit of randomisation. A third, smaller, integrated cohort arm (4:4:1 random allocation) contributes to understanding case-mix, but not trial outcomes. Participants are adults living with HIV not currently on TB treatment. The intervention (DCXR-CAD plus urine FujiLAM plus usual care) is compared to usual care alone. The primary outcome is proportion of participants started on tuberculosis treatment by day 56, with secondary outcomes of mortality (time to event) measured to to 56 days from enrolment, proportions with undiagnosed tuberculosis at death or hospital discharge and comparing proportions with enrolment-day tuberculosis treatment initiation. Discussion Both DCXR-CAD and FujiLAM have potential clinical utility and may have complementary diagnostic performance. To our knowledge, this is the first randomised trial to evaluate these tests among hospitalised PLHIV.

Guideline Adherence of Asymptomatic Bacteriuria Could Be Improved among General Practitioners in The Netherlands: A Survey Study

Asymptomatic bacteriuria (ASB) is a common finding in certain populations. This study assessed general practitioners’ (GPs’) knowledge about ASB and their current clinical practice regarding urine testing. Methods: An online survey was used for GPs in the Netherlands from October to December 2020. Results: In total, 99 surveys were included in the analyses. All GPs strongly agreed with the statements about their knowledge and self-confidence regarding urine diagnostics and treatment of ASB. The median knowledge score was 4 out of 6 (IQR 2 to 6). Most GPs (64 of 92; 70%) followed the guideline for the choice of urine diagnostics and reported appropriate indications for urine testing. However, 71/94 (75.5%) GPs would treat patients for ASB if they have diabetes mellitus. Further, 34 (37%) of 92 participants would inappropriately repeat a urine test after a patient was treated for a urinary tract infection (UTI). One-third of the GPs responded that ASB was insufficiently addressed within the guidelines for UTI. Conclusion: These results indicate that knowledge about ASB could be improved in primary care in the Netherlands, mainly in diabetic patients that have ASB, as well as for follow-up tests after treatment for UTI.

Dispersive liquid–liquid microextraction of 11-nor-Δ9-tetrahydrocannabinol-carboxylic acid applied to urine testing

Aim: THC-COOH is the major metabolite of Δ9-tetrahydrocannabinol commonly tested in urine to determine cannabis intake. In this study, a method based on dispersive liquid–liquid microextraction was developed for testing THC-COOH in urine. Materials & methods: Hydrolyzed urine specimens were extracted via dispersive liquid–liquid microextraction with acetonitrile (disperser solvent) and chloroform (extraction solvent). Derivatization was performed with N,O-Bis(trimethylsilyl)trifluoroacetamide with 1% trichloro(chloromethyl)silane. Analysis was performed by GC–MS/MS. Results: The method showed acceptable linearity (5–500 ng/ml), imprecision (<10.5%) and bias (<4.9%). Limits of detection and quantitation were 1 and 5 ng/ml, respectively. Twenty-four authentic samples were analyzed, with 22 samples being positive for THC-COOH. Conclusion: The proposed method is more environmentally friendly and provided good sensitivity, selectivity and reproducibility.

Neonatal Proteinuria in Calves—A Quantitative Approach

Urine testing is a convenient, non-invasive method of obtaining information about body functions. Depending on the intended purpose, urine testing may be qualitative and/or quantitative. Urine analysis can also include proteins. There are no data in the literature on the occurrence of proteinuria in healthy neonatal calves. The present study was the first that aimed to quantify the hypothesis of proteinuria occurrence in these animals in the first week of life, to assess its intensity and dynamics and to understand the underlying causes of proteinuria in healthy calves. The research was carried out on 15 healthy calves in the first seven days of life. Calves were catheterized to determine minute diuresis. Total protein concentration was determined in blood plasma and urine. Urine proteins were separated by electrophoresis (SDSPAGE) and their concentration and percentage were determined by densitometry using an image archiving and analysis software. The separated proteins were divided into three groups according to molecular weight for albumin, LMW and HMW proteins. The results were standardized per 1 m2 of body surface area and statistically analyzed. Neonatal proteinuria was demonstrated in healthy calves, mainly resulting from the high concentration of LMW proteins in the urine. Their percentages decreased significantly from 84.46% on the first day of calves’ life to 64.02% on day 7. At the same time, a statistically significant increase was observed in the proportion of albumin and high molecular weight proteins in urine total protein. Albumin percentage increased from 9.54% (on day 1) to almost 20% (on day 7), while the proportion of HMW proteins increased from 6.68% to 18.13%, respectively. The concentration of total protein in the urine of newborn calves amounted to 14.64 g/L and decreased statistically significantly during the first 72 h of postnatal life, stabilizing at the level of 3–4 g/L. The mean value of total protein excretion in the first week of life was 4.81 mg/min/m2 (i.e., 6.93 g/24 h/m2). The analysis of protein concentration in the urine and its excretion, as well as changes in urinary excretion of the tested protein fractions, indicated that neonatal proteinuria in healthy neonatal calves was tubular (i.e., main reason is the reduced absorption of proteins in nephrons). In addition, research showed that there was a rapid improvement in resorptive mechanisms in tubular cells. It should be assumed that the filtration barrier in the kidneys of these animals after birth is morphologically prepared to retain high molecular weight proteins. It seems that the increased permeability of the filtration barrier in the glomeruli does not necessarily indicate the immaturity of the kidneys, but may indicate the kidneys’ adaptation to excess protein removal from the body during feeding with high-protein food (colostrum), with an open intestinal barrier enabling protein absorption from the gastrointestinal tract to the blood.

Utility of Urinalysis as a Follow-up Surveillance Tool in Nonmuscle Invasive Bladder Cancer

Purpose: To evaluate the association between microscopic hematuria (MH) detected by surveillance urinalysis and cancer recurrence in nonmuscle invasive bladder cancer (NMIBC) patients.Materials and Methods: A total of 1,082 NMIBC patients who underwent transurethral resection of bladder tumor (TURB) procedures at Asan Medical Center between January 2017 and December 2019 were included. We retrospectively reviewed the follow-up data for these cases including cystoscopy, urinalysis, and urine cytology. The association between urine testing and cancer recurrence was assessed by both univariable and multivariable logistic regression analysis.Results: The study patients had a median age of 68 years (interquartile range, 60–75 years) and comprised 898 men and 184 women. Among the 1,428 TURB procedures conducted in this series, 548 of the lesions (38.4%) were diagnosed as low-grade and 880 (61.6%) as highgrade cancers. A total of 3,309 follow-up cystoscopies were conducted during the study period and were divided into high-grade (HG) (2,011 cases) and low-grade (LG) (1,298 cases) groups according to the latest TURB pathology. MH was found to have a statistically significant association with NMIBC recurrence in both the LG (odds ratio [OR], 1.57; 95% confidence interval [CI], 1.107–2.223; p=0.011) and HG (OR, 1.90; 95% CI, 1.434–2.517; p<0.001) groups.Conclusions: Urinalysis during follow-up may provide important information on cancer recurrence in NMIBC patients.

35. Acceptability of Proposed Stewardship Interventions to Reduce Preoperative Screening and Treatment of Asymptomatic Bacteriuria

Background In 2019, the IDSA Clinical Practice guidelines on asymptomatic bacteriuria (ASB) recommended that clinicians no longer screen or treat patients for ASB before non-urological surgeries. However, it remains to be seen whether these guideline recommendations alone will produce changes in practice. Understanding clinical decision-making about preoperative urine screening and treatment can help design effective interventions to facilitate guideline concordance and support antibiotic stewardship. Our project objective was to qualitatively assess barriers and facilitators to reducing preoperative urine testing and treatment. Methods We conducted semi-structured interviews with 24 participants (surgeons, advance practice providers, pharmacists, infectious disease physicians, epidemiologists) at 4 Veterans Administration hospitals. We solicited feedback on 4 proposed interventions (substitution, lab restrictions, audit and feedback, interactive workshop), and invited suggestions on other interventions. Three researchers separately coded 20% of interview notes to sort responses to each intervention into acceptable, possibly acceptable, and not acceptable. The team then compared coding, resolved differences by consensus, and refined the code dictionary to ensure intercoder agreement; then each member coded one third of remaining notes. Results Participants expressed concerns about de-implementing routine urine testing and treatment for specific procedures and specialties (e.g., cardiothoracic). Some actively sought to identify and treat ASB. Participants found audit and feedback and substitution of different infection-control practices most acceptable. Participants suggested changes to make interventions more acceptable or feasible (e.g., tailoring to procedure, educational tailoring). Participants also identified new potential interventions (e.g. order set changes, collaborative decision making, education on potential harms, identification of testing costs). Table 1. Acceptability of Proposed Interventions by Percentage of Participants. Percentages Do Not Add up to 100% Because Some Interviewees Did Not Answer Every Question. Conclusion Interventions to optimize urine screening and treatment for patients undergoing surgeries may require tailoring for surgical specialties, and should address clinical concerns about intervention feasibility. Disclosures Kalpana Gupta, MD, MPH, Abbott (Shareholder)DBC Pri-Med (Consultant)Glaxo Smith Kline (Consultant)Moderna (Shareholder)Nabriva Therapeutics (Consultant)Pfizer (Other Financial or Material Support, Grant to the institution)Qiagen (Consultant)Rebiotix (Consultant)Spero Therapeutics (Consultant)Utility Therapeutics (Consultant) Daniel Suh, MS MPH, General Electric (Shareholder)Merck (Shareholder)Moderna (Shareholder)Smile Direct Club (Shareholder) Bruce Alexander, PharmD, Bruce Alexander Consulting (Independent Contractor) Marin Schweizer, PhD, 3M (Grant/Research Support)PDI (Grant/Research Support)

85. Evaluation of Urinalysis and Urine Culture Use at a Community Health-system

Background The Infectious Diseases Society of America asymptomatic bacteriuria (ASB) guidelines recommend against screening for or treating ASB in most patients without symptoms of a urinary tract infection (UTI). The purpose of this study was to characterize current urine testing practices and their potential impact on identification and treatment of asymptomatic bacteriuria on hospitalized adults. Methods This retrospective, point prevalence study conducted at a 4 hospital community health-system that included all inpatients ≥ 18 years old present on November 13th, 2019. Patients were excluded if they were admitted or transferred to either a labor & delivery or mother-baby unit. A chart review was performed for a sub-group of patients with abnormal urine testing, with a target sample size of 200 (n=50 from each hospital). The primary outcome was the prevalence of patients with a urinalysis, urine culture, or both performed during their admission. Secondary outcomes included abnormal urine testing in the overall cohort and symptomatology and antibiotic use in the sub-group (Figure 1). Results 947 patients met inclusion criteria. Of those patients, 516 (54%) had urine testing performed during their admission. 322 (34%) patients had abnormal urine testing results (Table 1). In the sub-group, 192 patients with abnormal urine tests were included. Antibiotics with a documented indication of UTI were administered to 66 (34%) patients. Of those given antibiotics with a UTI indication, 49/66 (74%) did not have documented signs or symptoms of a UTI (Figure 2). Conclusion Urine testing was performed on the majority of admitted adult patients. Unnecessary testing likely contributes to guideline discordant screening and treatment of ASB. Future studies are needed to identify effective diagnostic stewardship interventions to decrease screening and treatment of ASB. Disclosures Ashley Wilde, PharmD, BCPS-AQ ID, Nothing to disclose