case study about urinalysis with discussion

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• URINALYSIS CASES AND CRITICAL THINKING

Gerald D. Redwine, PhD, MT(ASCP)

The physical and chemical examination of urine samples plays an essential role in the diagnosis of patients’ pathological conditions. However, the sheer number of routine urinalysis can minimize their significance, especially considering that most analyses are automated, which can foster complacency for less than apparent problems. As a result of seemingly more critical concerns, one may defer the interpretation for the clinician to assess. Nevertheless, detecting abnormal results and possible causes is required, regardless of whether the analysis was manual or automated. Knowing the effects of pigmentation, drugs, pH, and ascorbic acid, for example, are samples that always need attention.

Manual analysis is further complicated, with several idiosyncrasies innate to manufacturers. For example, differences in popular brands, such as, Multistix, that requires reading each chemical pad at the specific time indicated. But the Chemstrip and vChem strips readings are stable between one and two minutes, except leukocytes read at two minutes, all necessitating the need for special attention to the manufacturers’ instructions. Concerning ascorbic acid, knowing that Chemstrip eliminates ascorbic acid interference with blood by overlaying the pad with iodate, and the vChem strips have a detection pad for the substance; in contrast, knowing that the Multistix has neither, is essential. Finally, knowing to ignore the different coloration on the perimeter of the pad on all strips and asking for a recollect on extremely high pH is also vital.

How are the critical thinking skills needed for a urinalysis assessment best developed? In academia, it seemed best, following initial training, to have students complete weeks of daily intensive practice of the entire urinalysis (physical, chemical, and microscopic) in an open lab setting on multiple patient samples. In combination with these analyses, they were given case studies like the ones administered later in a practical examination. The following is a composite of the answer stating what they thought was the most probable cause to three of the 17 cases given on their exam, using Multistix, with further comments in parenthesis. Assessments constrained the students to answer the question under the given condition, knowing they would ask for a recollect in some instances.

• What would explain the apparent disagreement between the nitrite and leukocyte reaction?
• What accounts for the clarity of the sample in the chemical examination?
• What does the Acetest suggest about the chemical reactions, based on literature?
• Non-nitrate reducing organism. (i.e., bacteria, yeast, trichomonads, and chlamydia) Or Trauma. (Other less likely possibilities.)
• Large blood. (Also slightly enhanced the protein.)
• More sensitive because of the added glycine. (Glycine detects acetone. vChem strips have the same.)

• What could explain the single most unexpected finding within the chemical reactions?
• What could account for the protein and SSA discrepancy?
• What should the adjusted strip value read?
• What is the definitive source(s) for reporting the final specific gravity (SG) reading (manual/analyzer/and or name another source) on this specimen?
• With an SG = 1.040, what value is the final specific gravity?
• Negative leukocytes could result from any or all three of the following. 1) Alkalinity 2) >3g/dL glucose 3) High specific gravity.
• Alkaline pH can cause a false positive protein; also, the blood that is missing in the supernatant for the SSA could account for the 2+ SSA.
• Because pH is ≥ 6.5, then add .005 to the dip strip value. Strip SG = 1.035 . (Multistix only)
• Because of the ≥ 100 protein, then run on the refractometer. (Total Solid (TS) meter/Refractometer.)
• Subtract 0.003 for every 1 g/dl protein; subtract 0.004 for every 1 g/dl glucose. Report SG: 1.026 .

• What could explain the disagreement that exists within the chemical reactions?
• Explain the correlation between chemical reactions and the SSA?
• What are the two specific adjustments needed for the specific gravity?
• What is the final strip specific gravity?
• A non-nitrite reducing microbe such as Trichomonas or Chlamydia . Or postrenal trauma. (Other nitrite negative possibilities. Also, if not for the trace protein, ascorbic acid is suspect.) Best observation: Yellow-Green ~ Biliverdin. False-negative bilirubin. Hence, the need for a recollection and run on a fresh sample to ascertain the true values.
• Expected the SSA to be greater. Alkaline pH can cause a false positive protein, or in this case, falsely increase the value.
• Because pH is ≥ 6.5, then add .005 to the dip strip value. Because of the ≥ 100 protein, then run on the refractometer. TS (Total Solid) meter/Refractometer. (Multistix only)
• Strip SG = 1.015.

Responses to the open lab concept, despite significantly more than usual time commitment on behalf of all involved, and reagents, the sacrifices were met with positive feedback from the students on superseding their learning outcomes. The learning outcomes summarized is critical thinking applied to urinalysis case studies.

Reference: Brunzel, N. A., MS, MLS(ASCP) CM . Fundamentals of Urine and Body Fluid Analysis , 4th Edition

Gerald D. Redwine is an associate professor at Texas State University Clinical Laboratory Science Program in San Marcos, Texas.

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Article Contents

Introduction, case report, conflicts of interest statement, ethical approval.

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Educational case: a patient with proteinuria

• Article contents
• Figures & tables
• Supplementary Data

Christopher N Kassam, Vivian W M Yiu, Meryl H Griffiths, William G Petchey, Educational case: a patient with proteinuria, Oxford Medical Case Reports , Volume 2020, Issue 6, June 2020, omz148, https://doi.org/10.1093/omcr/omz148

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This is an educational case suitable for all readers, but aimed particularly at trainees preparing for MRCP. Using the example of a patient presenting to clinic with proteinuria, aspects of differential diagnosis, pathology and management are explored.

A 37-year-old male Caucasian administrator presented to general nephrology clinic after his GP noted 3+ proteinuria on urinalysis.

His symptoms included tiredness and frothy urine for 6 months. He had not experienced any haematuria, lower urinary tract symptoms, flank pain, ankle swelling, breathlessness or recent weight change. He had a past medical history of obstructive sleep apnoea and was not diabetic. He took no regular medications and had no known allergies. He had a family history of cardiovascular disease on his father’s side and lung cancer on his mother’s side. There was no family history of renal disease. He had never smoked. A recent HbA1c performed by his GP was 41 mmol/mol (5.9%).

On examination, the patient’s BMI was 38 kg/m 2 , and his blood pressure was 133/76 mmHg. There was no detectable peri-orbital or pedal oedema. His JVP was not raised. His chest was clear on auscultation and his kidneys were not palpable. There was no rash. Urinalysis confirmed 3+ proteinuria and no haematuria.

Diabetic nephropathy

Membranous nephropathy

Granulomatosis with polyangiitis

Lupus nephritis (class V)

Alport syndrome

Explanation: Membranous nephropathy is an immune-mediated glomerulopathy which is the commonest primary cause of nephrotic syndrome in Caucasian adults [ 1 ]. Diabetic nephropathy is a common cause of proteinuria, but HbA1c is not elevated and it is unusual for previously undiagnosed diabetes to present with proteinuria in the absence of other symptoms. Granulomatosis with polyangiitis is rare and tends to present with systemic malaise and multi-organ involvement; urinalysis typically shows both protein and blood. Class V lupus nephritis is a possibility in this case, but is less common than membranous nephropathy, and would often cause haematuria in addition. Alport syndrome is a genetic disorder (usually X-linked) caused by defects in type IV collagen synthesis; it is unlikely in the absence of a family history or deafness, and usually presents with progressive renal impairment rather than proteinuria. There is some evidence that primary focal segmental glomerulosclerosis may be overtaking membranous nephropathy as the leading primary cause of nephrotic syndrome, particularly in black patients; however, FSGS was not an option in this question [ 2 ].

Investigations were performed (Table 1). Additionally, screening tests for HIV, hepatitis B and hepatitis C were negative. Renal ultrasound demonstrated that both kidneys were of normal size, with no cysts or masses (bipolar length LEFT 11.3 cm, RIGHT 11.7 cm).

> 3.5 mg/mmol

> 30 mg/mmol

> 150 mg/mmol

> 250 mg/mmol

> 300 mg/mmol

Explanation: 24-hour urinary protein excretion is no longer routinely measured due to impracticality and inaccuracies in timing urine collection; it has largely been replaced by the spot measurement of albumin:creatinine or protein:creatinine ratio (PCR). An ACR of > 250 mg/mmol corresponds to a 24-hour urinary protein excretion of > 3.5 g, the threshold for nephrotic-range proteinuria. If urinary PCR is used, the threshold is 300 mg/mmol. An ACR of < 2.5 mg/mmol (males) or < 3.5 mg/mmol (females) is considered normal, while an ACR of 2.5–30 mg/mmol (males) or 3.5–30 mg/mmol (females) indicates microalbuminuria. Note that microalbuminuria is not usually detected by urine dipsticks.

A renal biopsy was performed to establish the underlying cause of the patient’s proteinuria. A biopsy of his left kidney was successfully taken. Representative sections are shown in Fig. 1 .

Representative sections from the biopsy of the patient’s left kidney, H&E stain.

Investigation results

Congo red staining was negative. Immunofluorescence showed some staining for IgM and complement C3 in sclerotic glomerular lesions, but was otherwise unremarkable.

Amyloidosis

Obesity-related glomerulopathy

Primary focal segmental glomerulosclerosis

Explanation: Obesity-related glomerulopathy (ORG) typically presents with sub-nephrotic proteinuria in patients with BMIs > 30 kg/m 2 . Nephrotic syndrome is not usually seen, even when the proteinuria reaches nephrotic range [ 3 , 4 ]. In case series, the prevalence of renal impairment at diagnosis has ranged from 33 to 44%, with 10–33% of patients eventually progressing to end-stage kidney disease [ 5–7 ]. However, in early stages of the disease, creatinine may be normal or low due to glomerular hyperfiltration. Pathologically, renal biopsy histology demonstrates glomerulomegaly and focal segmental glomerulosclerosis (predominantly perihilar in distribution), with non-specific immunofluorescence findings. In this case, the biopsy findings are not typical of either amyloidosis or membranous nephropathy. In addition, negative Congo red staining and myeloma screen make amyloidosis unlikely, while anti-phospholipase A2 receptor antibody is positive in 70% of patients with primary membranous nephropathy [ 1 ]. While the histological appearance of ORG has some similarities to that of diabetic nephropathy (so-called ‘diabetoid’ changes), this patient’s HbA1c indicates normal glycaemic control. Primary FSGS remains a possibility; however, patients commonly present with nephrotic syndrome, glomerulomegaly is not usually seen and a perihilar distribution of sclerotic lesions is typically associated with secondary (adaptive) causes of FSGS such as ORG. It is essential to distinguish between primary and secondary FSGS so as to avoid treating obese patients with high-dose corticosteroids for prolonged periods. Electron microscopy may further assist in making this distinction: typically in primary FSGS podocyte foot processes are diffusely effaced from early in the disease course, whereas in secondary FSGS, foot process effacement is segmental and develops more slowly [ 8 ].

Bariatric surgery

Spironolactone

Structured weight-loss programme

Watchful waiting

Explanation: There is no definitive evidence available as yet on the management of ORG. However, Renin-Angiotensin-Aldosterone blockade with an angiotensin converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) is the most evidence-based intervention for reducing proteinuria and preventing progression to end-stage renal disease [ 3 ]. Indeed, NICE recommends that all patients with ACR > 70 mg/mmoL due to any cause should be offered an ACE inhibitor or ARB [ 9 ]. There is also some evidence that weight-loss interventions (particularly bariatric surgery) may induce rapid improvements in glomerular hyperfiltration and proteinuria, both in patients with ORG and more broadly in obese patients with CKD [ 3 ]. However, the literature on weight-loss interventions suffers from flaws in study design and limited follow-up, and provides little evidence regarding long-term progression to end-stage renal disease.

The patient was started on ramipril 5 mg OD and advised to return for 6-monthly review in nephrology clinic. After 12 years, his BMI had increased to 41 kg/m 2 , his serum creatinine had progressively risen to 622 μmol/L and his eGFR had fallen to 8 mL/min/1.73 m 2 . He was referred to the low-clearance clinic to discuss renal replacement therapy (RRT).

Automated peritoneal dialysis

Conservative management

Continuous ambulatory peritoneal dialysis

Intermittent haemodialysis

Kidney transplant

Explanation: While all patients should be offered the option of conservative management, this will not usually be the first choice in a young patient. Transplantation offers a clear survival benefit over any modality of dialysis irrespective of BMI, and current NICE guidelines suggest that patients should not be excluded from transplantation on the basis of BMI alone [ 10 , 11 ]. Kidney transplant is, therefore, the most appropriate option. However, BMI >  35 is associated with an increased risk of adverse outcomes including surgical complications and graft loss, and in practice, in the context of donor scarcity, many centres exclude very obese patients from transplantation or require weight loss prior to transplant listing [ 12 ]. Clinicians will, therefore, often find themselves offering other RRT modalities for obese patients, either long-term or as a bridge to transplant. There is no high-quality evidence regarding the effect of peritoneal dialysis versus haemodialysis on mortality or quality of life in adults, and the patient should be offered the choice of haemodialysis and peritoneal dialysis modalities depending on local service availability [ 13 ]. However, from a technical perspective, insertion of a peritoneal dialysis catheter would be difficult for a patient with BMI 41 kg/m 2 , potentially requiring a pre-sternal catheter, which is not available at all centres.

The pathogenesis of ORG is complex and incompletely understood. Obesity is known to be associated with increased circulating levels of angiotensin II, due in part to angiotensinogen synthesis in adipose tissue [ 14 ]. Increased angiotensin II results in efferent arteriole constriction and afferent arteriole dilatation (both directly and via tubuloglomerular feedback), leading to glomerular hyperfiltration. Increased glomerular pressure is thought to lead first to glomerulomegaly and eventually to podocyte detachment and FSGS lesions. There is also evidence that insulin resistance and alterations in circulating adipokine concentrations may directly contribute to podocyte loss [ 3 ].

The prevalence of obesity (defined as BMI > 30) among adults in England has risen from 15% in 1993 to 26% in 2016; similar rates are found in other parts of the UK [ 15 ]. All physicians will undoubtedly be required to manage ever-increasing numbers of obese patients. The obesity epidemic has important implications for renal medicine. Obesity is a major risk factor for both malignant and non-malignant renal disease: the relative risk for end-stage renal failure in obesity is 4.07, while 26% of non-malignant renal disease in industrialised countries is attributable to being overweight [ 16 ]. While much of this excess risk is due to the complications of obesity such as diabetes and hypertension, a sub-population of obese patients develop proteinuria in the absence of other risk factors. Studies on these patients have defined ORG as an independent pathological entity. Indeed, in the absence of routine renal biopsy, some evidence suggests that up to 10% of cases of presumed diabetic nephropathy may in fact be wholly or partly due to ORG [ 17 ].

As obesity rates continue to rise globally, the incidence of ORG is likely to rise in tandem. Being alert to the clinical presentation of ORG may facilitate early intervention with ACE inhibitors, helping to slow progression to end-stage kidney disease in these patients.

No conflicts of interest.

No funding.

No ethical approval required.

No consent required.

Couser WG . Primary membranous nephropathy . Clin J Am Soc Nephrol 2017 ; 12 : 983 – 97 .

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National Institute for Health & Care Excellence ( 2014 ). Chronic kidney disease in adults: assessment and management (NICE guidelines CG182) . Available at: https://www.nice.org.uk/guidance/cg182/resources/ chronic-kidney-disease-in-adults-assessment-and-management-pdf-35109809343205 (19 February 2019, date last accessed).

National Institute for Health & Care Excellence ( 2018 ). Renal replacement therapy and conservative management (NICE guidelines NG107) . Available at: https://www.nice.org.uk/guidance/ng107/resources/ renal-replacement-therapy-and-conservative-management-pdf-66141542991301 (10 February 2019, date last accessed).

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• Published: 16 March 2021

Prediction of urine culture results by automated urinalysis with digital flow morphology analysis

• Dokyun Kim 1 , 2 ,
• Seoung Chul Oh 1 ,
• Changseung Liu 1 , 2 , 3 ,
• Yoonjung Kim 1 ,
• Yongjung Park 1 &
• Seok Hoon Jeong 1 , 2  

Scientific Reports volume  11 , Article number:  6033 ( 2021 ) Cite this article

5315 Accesses

3 Citations

Metrics details

• Bacterial infection
• Diagnostic markers
• Predictive markers
• Urinary tract infection

To investigate the association between the results of urinalysis and those of concurrent urine cultures, and to construct a prediction model for the results of urine culture. A total of 42,713 patients were included in this study. Patients were divided into two independent groups including training and test datasets. A novel prediction algorithm, designated the UTOPIA value, was constructed with the training dataset, based on an association between the results of urinalysis and those of concurrent urine culture. The diagnostic performance of the UTOPIA value was validated with the test dataset. Six variables were selected for the equation of the UTOPIA value: age of higher UTI risk [odds ratio (OR), 2.069125], female (OR, 1.400648), nitrite (per 1 grade; OR, 3.765457), leukocyte esterase (per 1 grade; OR, 1.701586), the number of WBCs (per 1 × 10 6 /L; OR, 1.000121), and the number of bacteria (per 1 × 10 6 /L; OR, 1.004195). The UTOPIA value exhibited an area under the curve value of 0.837 when validated with the independent test dataset. The UTOPIA value displayed good diagnostic performance for predicting urine culture results, which would help to reduce unnecessary culture. Different cutoffs can be used according to the clinical indication.

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Introduction.

Urinary tract infection (UTI) is the most common bacterial infection acquired in the community and in healthcare facilities. The prevalence of UTI is estimated to be 11% of the overall population, and almost half of adult women suffer from UTI at least once in their lifetime 1 , 2 . Clinical manifestations of UTI are mostly mild; however, the disease could develop serious complications, especially in certain high-risk populations including infants, pregnant women, and aged population 3 . Therefore, early diagnosis and empirical antimicrobial treatment is essential to improve clinical outcomes of patients with UTI 4 .

The gold standard for definitive diagnosis of UTI is detection of the pathogen by bacterial culture of a urine specimen 5 , and an antimicrobial susceptibility profile can be obtained by testing clinical isolates. However, urine culture is a time-consuming procedure, and the microbial spectrum of causative organisms in UTIs is narrow. Therefore, routine cultures are often not necessary to manage patients with uncomplicated UTIs, and only urinalysis either by test strip analysis and/or sediment analysis are recommended for the decision of patient management 6 . Among the components of test strip analysis, leukocyte esterase (LE) and nitrite are commonly used to diagnose UTI in routine clinical practices. Urine LE positive indicates pyuria, and urine nitrite positive indicates the presence of nitrate-reducing bacteria. However, diagnostic performance of these tests is not sufficiently high to be used alone due to limitations of the test principle 7 .

Test strip analysis is traditionally done by the dipstick based on physicochemical reactions, and the results are interpreted using a reflectometer. Automated urinalysis systems including sample preparation, aliquot, and reading have been introduced to improve test throughput and efficiency and to reduce labor and time. In addition, microscopic examination of urine sediment is also widely used to diagnose urinary tract diseases by identifying various types of cells, casts, and crystals in a urine sample. However, manual microscopic examination is a time-consuming procedure and requires expertise to maintain consistency of the result interpretation. Recently, different types of automated urine sediment analysis systems have been introduced. Among them, the iQ200 (Beckman Coulter Inc., Brea, CA, US) is an automated digital imaging-based system that uses flow morphology analysis to classify particles in a urine sample based on multiple parameters including size, shape, contrast, and texture. This instrument has exhibited satisfactory analytical performance for the quantitation of red blood cells (RBCs), white blood cells (WBCs), and epithelial cells compared with other automated sediment analysis systems and manual microscopic methods 8 .

Here, we evaluated an association between the results of urinalysis obtained by the iRICELL system including the iQ200 automated urine sediment analysis instrument with results of concurrent urine cultures. We also aimed to construct a simple but practical prediction model for the positive urine culture with the results of urinalysis including automated urine sediment analysis.

Patient characteristics and urine culture results

The median (1st–3rd quartiles) age of the 42,713 patients was 56 (24–69), and 38.7% (n = 16,519) of the patients were included in the high-risk age group (Table 1 ). Almost half (50.7%, n = 21,635) of the subjects were male, and two thirds (70.3%, n = 30,036) of the subjects were hospitalized patients. The median (1st–3rd quartiles) difference in reception time between urinalysis and urine culture was 0.3 (0.1–19.1) minutes, and the median difference in report time was 39.8 (23.7–62.7) hours. The results of urine culture were positive for 17.1% (n = 7292) of the patients, and 89.2% (n = 6506) of these were positive with a single pathogen, 4.5% (n = 325) with a single pathogen and a possible pathogen below the threshold, 3.3% (n = 220) with a single pathogen and a single normal flora, and 3.0% (n = 220) with two pathogens. The most common pathogen isolated in this study was Escherichia coli (54.9%, n = 4121 among 7512) followed by Enterococcus faecalis (11.7%, n = 878), Klebsiella pneumoniae (6.5%, n = 491), and Enterococcus faecium (5.3%, n = 400) (Supplementary Table 1 ). Patients in the urine culture-positive group exhibited a significantly higher proportion of high-risk age group (53.3% vs 35.7%, P  < 0.0001) and lower proportion of males (33.8% vs 54.1%, P  < 0.0001) than the urine culture-no growth or contamination group (Table 1 and Supplementary Table 2 ).

The results of urinalysis according to the culture results

The results of test strip and sediment analyses according to the urine culture results are summarized in Table 1 . Except for urine glucose, all parameters were significantly different between the two groups. By the multivariate binary logistic regression, three patient factors including high-risk age [odds ratio (OR), 1.967], female (OR, 1.483), and hospitalization (OR, 1.174) were significantly associated with positive results of the urine culture ( P  < 0.0001 for each) (Table 2 ). Among the test strip results, pH (OR, 1.061 per 1.0 increase; P  = 0.0007), nitrite (OR, 3.952 per 1 grade increase; P  < 0.0001), and LE (OR, 1.736 per 1 grade increase; P  < 0.0001) were independent risk factors for positive urine culture. Among the parameters of automated sediment analysis, the numbers of RBCs (OR, 1.000 per 1 × 10 6 /L increase), WBCs (OR, 1.000 per 1 × 10 6 /L increase), epithelial cells (OR, 1.001 per 1 × 10 6 /L increase), and bacteria (OR, 1.006 per 1 × 10 6 /L increase) showed significant associations with positive results of the urine culture ( P  < 0.0001 for each).

Among the variables exhibiting significant associations with positive urine culture, six variables including age of higher risk (OR, 2.069125), female (OR, 1.400648), nitrite (OR, 3.765457 per 1 grade increase), LE (OR, 1.701586 per 1 grade increase), the number of WBCs (OR, 1.000121 per 1 × 10 6 /L increase), and the number of bacteria (OR, 1.004195 per 1 × 10 6 /L increase) were selected considering the effect size of each variable by multivariable binary logistic regression in the training dataset with 21,522 patients ( P  < 0.0001 for all variables; Supplementary Table 3 ). An equation to predict urine culture results was constructed with the constant and coefficients of independently significant variables as follows:

x 1  = 1, if a **patient is at high-risk age (≤ 1 or ≥ 70 years old), otherwise x 1  = 0

x 2  = 1 for female; x 2  = 0 for male

x 3  = grade of nitrite by test strip analysis (0.5 when the result is trace or weak positive)

x 4  = grade of LE by test strip analysis (0.5 when the result is trace or weak positive)

x 5  = number of WBCs by digital flow morphology analysis (1 × 10 6 /L)

x 6  = number of bacteria by digital flow morphology analysis (1 × 10 6 /L).

Diagnostic performance of the UTOPIA value

To validate the diagnostic performance of the UTOPIA value for predicting results of urine culture, ROC curves were constructed with the independent test dataset composed of 21,191 patients from different periods, and the AUC of the UTOPIA value was 0.837 (95% CI = 0.829–0.845), which is significantly higher than that of nitrite (AUC = 0.645; 95% CI = 0.637–0.653), LE (AUC = 0.758; 95% CI = 0.749–0.767), the number of bacteria (AUC = 0.753; 95% CI = 0.743–0.762), and the number of WBCs (AUC = 0.779; 95% CI = 0.769–0.789) ( P  < 0.0001 for all comparison, Fig.  1 ). In addition, the UTOPIA value also exhibited higher AUC value than the other models including the Model 1 (AUC = 0.811; 95% CI = 0.802–0.820) which consisted of WBCs and bacteria counts by automated sediment analysis, and the Model 2 (AUC = 0.817; 95% CI = 0.808–0.826) which was composed with LE, nitrite, and the variables of Model 1 (Fig.  1 ).

Receiver operating characteristics (ROC) curve analysis of the urinalysis in the prediction of urine culture positive results in the test dataset. The area under the curve (AUC) of the model 2 (combination of nitrite, leukocyte esterase, and WBC and bacteria counts) was higher than that of the model 1 (combination of WBC and bacteria counts) ( P  = 0.0002), and the UTOPIA value showed the highest AUC value among those of other tests ( P  < 0.0001).

When using > 15.11 as a cutoff for the UTOPIA value, which showed the highest Youden’s index, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 0.661, 0.862, 0.473, and 0.931, respectively (Table 3 ). A cutoff value of > 6.54 exhibited sensitivity of 0.950 and specificity of 0.330, while a cutoff value of > 34.21 showed specificity of 0.950 and sensitivity of 0.498.

Microscopic examination of urine particle is a useful tool for diagnosing UTI, although the gold standard for diagnosis is urine culture. To date, three different types of automated urine sediment analyzers have been introduced. Sysmex UF-1000i (Sysmex Corporation, Kobe, Japan) utilizes the flow cytometric method. This analyzer measures numbers of cells, bacteria, and casts by electrical impedance per flow sample volume, sizes the components by forward light-scatter, and nuclear and cytoplasmic characteristics using fluorescent dye 9 . Another instrument the cobas u701 (Roche Diagnostics International, Rotkreuz, Switzerland), which was first introduced as UriSed (77 Elektronika, Budapest, Hungary) 10 , takes 15 microscopic images per urine sample prepared in cuvettes that mimic glass slides used in manual microscopic examination, and the result images are analyzed by particle recognition software 11 . The iQ200 investigated in this study is an automated digital imaging-based system that uses flow morphology analysis. In previous studies, the iQ200 system showed reliable performance in counting RBCs, WBCs, and epithelial cells in terms of imprecision and linearity and showed good correlation with manual microscopic sediment analysis and other automated analyzers 8 , 12 , 13 .

There have been several studies to evaluate possible associations between the results of microscopic urine sediment examinations and those of urine culture. A meta-analysis for predicting positive urine culture by the results from the Sysmex UF-1000i or UF-100 systems showed good sensitivity, using the number of WBCs (pooled sensitivity, 0.87) and bacteria (pooled sensitivity, 0.92) counted by flow cytometry as indicators 14 . The number of bacteria in urine specimens obtained by Accuri C6 (BD Biosciences, San Jose, CA, US) showed good correlation with the results of urine culture when a cutoff value for urine culture positive was ≥ 10 5  CFU/mL 15 . A recent interlaboratory study exhibited that the absence of microorganisms in the iQ200 screen was the strongest solitary predictor for a negative culture result with a sensitivity of 90.5%, and higher sensitivity (95.2%) could be obtained by the algorithm based on the presence of microorganisms and the number of WBCs 16 . Another study with the iQ200 system exhibited an acceptable NPV of 97.7% and approximately 50% reduction of urine culture when using WBC ≥ 4/HPF as a cutoff in predicting urine culture results, but the PPV was only 24.5% in the same study 17 . The scoring system suggested by Foudraine et al., which was composed of clinical symptoms including dysuria and urgency and the number of WBCs obtained by the iQ200 analyzer, gave good diagnostic performance with a high AUC value of 0.950 for predicting positive blood cultures 18 . However, the diagnostic performance of a test could vary according to the characteristics and composition of cases and controls included in each study, thus it would be difficult to directly compare diagnostic performance among the studies. In addition, the definition of significant growth in urine culture in each study was different, thus it is also difficult to generalize the diagnostic performance of a test in the literature.

The UTOPIA value was designed to predict the positive urine culture with the variables including demographic conditions including age of higher risk for UTI and sex, results of urinalysis including nitrite, LE, and the numbers of WBCs and bacteria, and was validated with an independent dataset consisting of 21,191 patients in a different time period from the subjects in the training dataset. The distribution of the prevalence of UTI along with age was a J-shape with a higher frequency among the very young and a gradual increase with age, and the prevalence was significantly higher for women than men, as previously described 19 . By simply adding these two risk factors as variables of the prediction algorithm, the UTOPIA value exhibited better diagnostic performance than the other models those are consisted of only the variables from urinalysis (Fig.  1 ). This work provides a novel approach to predict the result of urine culture with the patients’ risk factors and the results of urinalysis. In addition, the UTOPIA value was designed with easy-to use data in order to incorporate into a laboratory information system easily, and thus can be automatically calculated immediately after urinalysis.

When validated with the independent test dataset, the UTOPIA value provided a good AUC value of 0.837 in the prediction of positive urine culture with high NPVs regardless of applied cutoffs. With the prevalence of our dataset (15.8%), the NPV was 0.978 (95% CI = 0.973–0.982) when applying a cutoff for the UTOPIA value of > 5.72, and 20.0% of total culture cases was estimated to be reduced at the expense of 2.2% of false negative results, i.e. 1—NPV based on the UTOPIA value (Table 3 ). Since the prevalence of the urine culture positive results can vary depending on factors such as the country, region, and patient age, appropriate cutoffs for the UTOPIA value would need to be applied for each clinical laboratory. The cost of urine culture according to the countries would be also considered. Using different cutoffs according to the allowable false negatives in each laboratory, the UTOPIA value would be utilized to reduce unnecessary urine cultures. Meanwhile, the utility of the UTOPIA value would be low if it is used for determining whether to start early empirical antibiotic treatment before the culture results are reported. In this instance, PPV of the UTOPIA value was 0.900 even when applying a high cutoff of > 92.61. Consequently, it can be applied to only 2.1% of the total patients because there would be only small number of patients showing positive results by the UTOPIA value with that high cutoff, and there would be false positive cases of 10.0%, i.e. 1—PPV, among the 2.1% of total patients as well.

In our data, the proportion of urine culture contamination cases was 28.0%, and they included in the control group to make a practical and accurate model for predicting the results of urine culture in actual clinical microbiology laboratories. In addition, the contamination group exhibited intermediate characteristics when comparing with urine culture negative and positive groups (Supplementary Table 2 ). If contamination cases were excluded from the regression model, the 1 diagnostic performance of UTOPIA value would be over-estimated.

One limitation of our study is that it was performed with the retrospective design, and 19.1% of total cases were excluded due to inaccurate quantitative results obtained by iQ200. Therefore, possible selection bias would be considered when interpreting our results. However, a large number of patients was included to minimize unpredictable bias and to enhance the statistical power with narrow CIs for the results in this study, and the study population was divided into two independent datasets including training and test datasets to improve the reliability and external validity of our results. Despite this effort, the validation of diagnostic performance of the UTOPIA value in a single hospital would be another limitation of this study, even though the independent dataset from a different time period was used in the validation. Multicenter evaluation for the diagnostic performance of the UTOPIA value calculated by the equation in this study would be helpful in the generalized application of the UTOPIA value. Additionally, we investigated the results from a single type of test strip analyzer and flow morphology analyzer among several automated urinalysis systems each utilizing different test principles and showing different semi-quantitative results for chemical parameters including LE. Separate prediction algorithms according to the type of urinalysis systems could also be developed by applying a similar approach to our study.

In conclusion, we designed a novel prediction algorithm for urine culture results based on the results of urine test strip analysis and digital flow morphology analysis, namely the UTOPIA value. The UTOPIA value showed good diagnostic performance with possibility of reducing unnecessary urine culture and flexibility to apply different cutoff values. This prediction algorithm can be used to predict urine culture results 1 to 3 days before the culture results are reported, and also has the advantage of being easily incorporated electronically into a laboratory information system. Further evaluation on the usefulness of the UTOPIA value in various clinical settings should be considered.

Materials and methods

Study design and patients.

From July 2015 to April 2020, a total of 62,656 patients were subjected to urine cultures for suspected UTIs in a tertiary hospital in South Korea. Among them, 52,772 patients were subjected to urinalyses within 6 h before or after urine culture, and 10,059 patients were excluded due to incomplete or inaccurate automated urine sediment analysis results. Finally, 42,713 patients were enrolled in this study (Fig.  2 ). Patients included in this study were divided into two datasets by the time of receipt: (1) a training dataset with 21,522 patients: cases requested between July 2015 and December 2017, and (2) a test dataset with 21,191 patients: cases requested between January 2018 and April 2020. This retrospective cross-sectional case–control study, designated the UTOPIA study (Urinalysis-based Timely and On-the-spot Prediction of Infection Algorithm), was designed to develop a simple and useful algorithm to predict urine culture results using results of urinalysis. Patient characteristics including demographic information and type of admission were investigated by reviewing electronic medical records. The protocol of this study was approved by the Institutional Review Board of Gangnam Severance Hospital (Approval No. 3-2020-0169), and the requirement of an informed consent of the participants was waived by the IRB. All methods used in this study were also performed in accordance with the relevant guidelines and regulations.

Study design and classification of cases. Solid lines indicate cases included in the analysis, while dotted lines represent excluded subjects.

Urine culture

The results of urine culture were retrieved from the electronic medical records. Urine culture was performed according to the standard protocol of the local microbiology laboratory. Briefly, one microliter of urine sample was inoculated on MacConkey agar and Blood agar, and the number of colonies was counted after an 18-h incubation to calculate bacterial load. Bacterial identification was performed using a Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometer (MALDI-TOF MS). To make an accurate prediction model for positive urine culture, the results of urine cultures were categorized into “Positive” and “No growth or contamination”.

Automated urinalysis with digital flow morphology analysis

The results of test strip analysis and sediment analysis by digital flow morphology analysis were retrieved from the electronic medical records. Automated urinalysis were performed using the iRICELL system (Beckman Coulter Inc., Brea, CA), which consisted of the iChem VELOCITY urine chemistry analyzer and the iQ200 SPRINT urine microscopy analyzer, following the manufacturer’s instructions. For the iQ200 instrument, approximately 1.3 mL of urine passes through a flow cell, and a digital camera captures 500 images of magnified sample. Then, the Auto-particle Recognition (APR) software (current version 7.1.4) interprets the captured images. The flow morphology interpretation with flags for suspicious errors or abnormal results by the APR software were reviewed with on-screen images by operators. Based on comprehensive consideration with on-screen images, previous urinalysis results of the same patient, and the test strip results concurrently obtained by iChem, cases with discrepant interpretations between operators and the analyzing software were subjected to manual microscopic sediment examination. If needed, the results for these cases were corrected as the number of cells per high-power field by manual microscopic examination, and were excluded from our study due to inaccurate quantitative values for RBCs, WBCs, and epithelial cells by the iQ200 analyzer in those cases. During the study period, three quality control materials for the iChem VELOCITY including IRISpec CA, CB, and CC (Beckman Coulter Inc.) and two materials for the iQ200 including iQ positive and negative controls (Beckman Coulter Inc.) were run every eight hours.

The high-risk age group for UTI was defined as patients younger than 2 years or older than 69 years considering high positive rates of urine culture according to national surveillance study 20 and positive rates of urine culture according to age in our data. A positive urine culture was determined when a single uropathogen (bacterial load ≥ 10,000 CFU/mL) or two uropathogens (bacterial load of each species ≥ 100,000 CFU/mL) were recovered. Uropathogens include Gram-negative bacilli, Staphylococcus aureus , Candida species, Enterococcus species, and Aerococcus urinae , as previously described 21 . Cases with more than three species recovered from urine culture were considered as contamination regardless of the quantity of bacterial growth 21 .

Statistical analysis

All statistical analyses were performed by Analyse-it for Microsoft Excel Method Evaluation Edition version 5.65.3 (Analyse-it Software, Ltd., Leeds, UK) and IBM SPSS Statistics 25 (IBM Corp., Armonk, NY, US). Patient characteristics and the results of urinalysis according to the groups classified by the urine culture results were compared with chi-square tests for categorical variables and Mann–Whitney U tests for continuous variables. Binary logistic regression with the results of urine culture as the dependent variable and those of urinalysis and patients’ characteristics as the multivariate independent variables was performed to determine the coefficient for each independent variable in the regression model. With the regression model equation, the UTOPIA value for each case in the test dataset was calculated to predict the probability for positive urine culture, and diagnostic performance of the UTOPIA value for the prediction of urine culture results was evaluated by calculating the area under the curve (AUC) value. All statistical analyses in this study were considered significant when the P value was < 0.05.

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Dokyun Kim, Seoung Chul Oh, Changseung Liu, Yoonjung Kim, Yongjung Park & Seok Hoon Jeong

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Dokyun Kim, Changseung Liu & Seok Hoon Jeong

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D.K.: writing-original draft and data analysis; S.C.O.: data collect and analysis; C.L.: data analysis; Y.K.: writing-review and editing; Y.P.: conceptualization, supervision, data analysis, and writing-review and editing; S.H.J.: conceptualization and supervision.

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Kim, D., Oh, S.C., Liu, C. et al. Prediction of urine culture results by automated urinalysis with digital flow morphology analysis. Sci Rep 11 , 6033 (2021). https://doi.org/10.1038/s41598-021-85404-1

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Neil Clancy, MD

Associate Chief of VA Pittsburgh Health System (VAPHS) and Opportunistic Pathogens Associate Professor of Medicine Director, Mycology Program Chief, Infectious Diseases Section VA Pittsburgh Health Care System Pittsburgh, Pennsylvania

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CME / ABIM MOC / CE

Clinical challenge: case studies in recurrent complicated utis.

• Authors: Neil Clancy, MD

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CASE 1: PATIENT HISTORY AND PRESENTATION

Tara is a 26-year-old Korean American woman who presents to the emergency department (ED) with fevers, chills, and right-sided flank pain, which developed acutely during the previous night. After she telephoned her healthcare provider in the morning about these symptoms, she was told to go directly to the ED. She is sexually active in a jointly monogamous relationship with her boyfriend of 2 years. Her only standing medication is an oral contraceptive, which she takes regularly. Her medical history is significant for an asymptomatic horseshoe kidney that was found incidentally and approximately 1 episode of cystitis per year, characterized by dysuria. After developing symptoms of cystitis, she telephones her healthcare provider and receives a prescription for ciprofloxacin or trimethoprim-sulfamethoxazole. She does not recall providing a urine sample for urinalysis or culture in the past. Her last episode of dysuria was 2 weeks ago, for which she took ciprofloxacin "for a couple of days." Her symptoms resolved without apparent incident. Since the onset of her presenting symptoms, she took 2 doses of ciprofloxacin that were left over from her previous prescription.

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Integrated clinical case discussions – a fully student-organized peer-teaching program on internal medicine

• Johannes Reifenrath   ORCID: orcid.org/0000-0002-7216-5926 1 ,
• Nick Seiferth 1 ,
• Theresa Wilhelm 1 ,
• Christopher Holzmann-Littig 1 , 2 ,
• Veit Phillip 3 &
• Marjo Wijnen-Meijer 1  

BMC Medical Education volume  22 , Article number:  828 ( 2022 ) Cite this article

2273 Accesses

Metrics details

In response to students´ poor ratings of emergency remote lectures in internal medicine, a team of undergraduate medical students initiated a series of voluntary peer-moderated clinical case discussions. This study aims to describe the student-led effort to develop peer-moderated clinical case discussions focused on training cognitive clinical skill for first and second-year clinical students.

Following the Kern Cycle a didactic concept is conceived by matching cognitive learning theory to the competence levels of the German Medical Training Framework. A 50-item survey is developed based on previous evaluation tools and administered after each tutorial. Educational environment, cognitive congruence, and learning outcomes are assessed using pre-post-self-reports in a single-institution study.

Over the course of two semesters 19 tutors conducted 48 tutorials. There were 794 attendances in total (273 in the first semester and 521 in the second). The response rate was 32%. The didactic concept proved successful in attaining all learning objectives. Students rated the educational environment, cognitive congruence, and tutorials overall as “very good” and significantly better than the corresponding lecture. Students reported a 70%-increase in positive feelings about being tutored by peers after the session.

Peer-assisted learning can improve students´ subjective satisfaction levels and successfully foster clinical reasoning skills. This highlights successful student contributions to the development of curricula.

Peer Review reports

The SARS-CoV2-pandemic´s strain on medical schools has been hard [ 1 , 2 , 3 ] since many stakeholders in medical education are both caregivers and instructors. With limited staff available for teaching [ 4 ] and reduced on-campus presence, many classes were moved to emergency remote teaching courses [ 5 , 6 ]. Emergency remote teaching is the “alternate delivery mode due to crisis circumstances” as opposed to well-planned online teaching [ 7 ].

At Technical University of Munich (TUM) most lectures, seminars, and bedside teachings werecanceled or moved to emergency remote teaching in the spring semester of 2020. Within the student council, the notion quickly gained traction that a peer-assisted learning (PAL) program ought to be established to alleviate pressure on faculty staff while providing students with a safe environment for the acquisition and training of their clinical reasoning skills.

Several universities have promoted PAL programs. It refers to the “development of knowledge and skill through explicit active helping and supporting among status equals” [ 8 ] . Benefits of PAL are i) a similar knowledge base and an understanding of obstacles while studying (cognitive congruence) [ 9 , 10 ], ii) a positive learning environment void of complicated student-instructor relationships due to similar social status (social congruence) [ 9 , 10 ] and iii) relieving pressure on faculty staff [ 11 ]. PAL has been employed in teaching anatomy, physiology, and biochemistry [ 12 ], as well as communication [ 13 ], physical examination [ 14 ], and other procedural skills [ 15 , 16 ]. There students have been shown to assume the roles of lecturers [ 17 ], clinical or practical teachers [ 18 ], mentors [ 19 ], learning facilitators [ 20 , 21 ], role models [ 21 ], and assessors [ 22 ]. In our study, we wish to introduce a curriculum that was fully designed, delivered, and evaluated by undergraduate students based on the Kern Cycle [ 23 ] with minimum intervention by faculty staff. We thus empower students to holistically assume all of the twelve roles of a teacher as proposed by Harden and Crosby in 2000 [ 24 ].

Targeted at students in the clinical phase of their studies, we developed the novel Integrated Clinical Case Discussions (ICCD) that emphasize the training of clinical reasoning skills that are at the heart of the recently released second edition of the competence-based German Medical Training Framework (GMTF) [ 25 ]. In accordance with the GMTF three central learning objectives were identified: i) transfer of clinical knowledge, ii) fostering of diagnostic management skills, and iii) enabling students to discuss findings and procedures in a team. Clinical Case Discussions (CCD) have been shown to enhance clinical and scientific reasoning skills [ 20 , 26 ], self-directed learning [ 26 ], and exchange with colleagues [ 27 ].

This study seeks to explore whether a peer-moderated clinical case discussion can improve students´ subjective satisfaction level with learning opportunities in case of emergency remote teaching.

Setting and participants

For their studies of internal medicine students at TUM attend two series of lectures in two consecutive semesters: In the spring semester of their first clinical year, there is a series of lectures on the cardiovascular and hematologic systems. In the subsequent fall semester, they hear a series of lectures on nephrology, gastroenterology, and endocrinology. Students are routinely requested to evaluate all lectures on a five-point Likert scale. When in the spring semester of 2020 all lectures were moved to an emergency remote teaching format, the mean evaluation of lectures on internal medicine dropped by 1.44 points as opposed to the six years prior (from 1.96 to 3.4, where 1 denoted the greatest and 6 the lowest level of satisfaction).

To provide their peers with an additional opportunity to review the lectures´ content, three students initiated the peer-moderated Integrated Clinical Case Discussions. In the ICCDs we applied a lecture´s content to a patient´s case with special emphasis on diagnostic and management skills in accordance with GMTF level 2 (i.e. clinical reasoning skills).

We prepared ICCDs for 12 topics in the fall semester of 2020 and 12 topics in the spring semester of 2021. For each topic we allocated two 90-min sessions in the week immediately following the general lecture on the topic. We were able to offer one face-to-face and one online tutorial for 11 topics. Due to hygiene regulations, the remaining 13 topics were discussed exclusively online twice a week. The time resources needed for one tutorial included i) 18 h for the tutor to prepare and hold the ICCD, ii) 3.5 h for the organizing students to recruit and mentor tutors as well as to evaluate and advertise the sessions and iii) 1.5 h of supervision by the physician (Fig.  1 ). The remuneration was 250€ per tutor and tutorial and 246.66€ for each organizing student per month (In the first year: authors JR and NS—15 months, TW—5 months. This was later reduced to one organizing student only.). Tutors were trained and supervised by specialist physicians as part of their regular teaching duties (1.5 h per session). Physicians were not reimbursed by the ICCD team. ICCDs were completely voluntary. We advertised ICCDs through weekly email alerts and a note in students´ schedules.

Workflow for the preparation of one ICCD session. Three parties are involved in the preparation and implementation of an ICCD session: an administrative unit consisting of the organizing undergraduate students (*) and the TUM Medical Education Center (†) (bottom row), tutors (middle row) and clinical supervisors (top row). Their respective tasks are indicated at the relative time points for the preparation of one ICCD. The allotted time frame for each task per one ICCD session is included in round brackets. For their first meeting tutors and supervisors are provided with a checklist (‡), i.e. to i) define content-focal points, ii) select an appropriate clinical case iii) define a clinical skill essential for the successful completion of the case, and to iv) provide the tutor with important clinical findings (e.g. laboratory findings, images)

Conception of the didactic concept

ICCDs followed cognitive learning theory. Each session was set as an interactive problem-based learning scenario ( Clinical Case Discussion ), that facilitated learners´ active participation to organize and conceptualize information [ 28 ]. To prompt students to access pre-existing knowledge ICCD sessions started with a voluntary entry-exam of five multiple-choice questions. The prefix Integrated reflects the close alignment of student-led tutorials and the lectures conducted by faculty staff. ICCDs did not seek to introduce new facts but to offer a platform for reviewing and applying the lecture’s contents to a clinical case. Each ICCD comprised two clinical cases in which at least one skill apart from history taking was trained (usually the interpretation of laboratory findings). Tutors and lecturers chose a clinical case from the lecturer´s clinical experience that matched the lecture. Tutors then prepared a powerpoint presentation (Microsoft Corp., Redmond, Washington, USA) to facilitate the case discussion, which was checked by the lecturer for medical content and by the organizing students for the didactic concept. Tutors delivered online sessions through a university zoom account (Zoom Video Communication Inc., 5.7.7, San Jose, California, USA) and—if under the Covid-regulations permissible—face-to-face in the lecturing hall. We instructed tutors to follow a modified version of Linsenmeyer´s approach [ 27 ] (Fig.  2 ). Briefly, tutees´ participation and teamwork were gradually increased by moving from anonymous multiple-choice questions to group discussions in breakout rooms and finally to discussing the ideal diagnostic procedures in the plenary session. An example of one case can be found in the supplementary material S1.

Typical outline of an ICCD session. We modified Linsenmeyer´s approach to stimulating interaction between students (Linsenmeyer, 2021). One ICCD session propagates along the x-axis from left to right. Several layers along the y-axis indicate the roles a tutor assumes at each time point, the teaching techniques they employ (examples provided below), and the level of interaction this is likely to be incentivize between tutees. A: Each session starts with a knowledge probe intended to activate students´ prior knowledge by asking five multiple-choice questions that participants must solve individually and anonymously. As indicated by the green triangle at the bottom of the figure this requires only a minimum level of interaction between students. B: Subsequently, tutors introduce the session´s clinical case and moderate a plenum discussion in which participants collectively take a patient´s history, determine an appropriate diagnostic algorithm, and list differential diagnoses. This gradually raises the level of interaction (upward slope of the triangle). C: In the next stage participants are assigned to break-out groups of two to four students in which they practice interpreting patient-specific clinical findings, lab results or different image modalities. Tutors switch from group to group to help if needed. D: Finally, the breakout groups meet back in the plenum and discuss their findings and differential diagnoses under the tutor´s moderation. We rated this as the most demanding level of interaction as it requires students to present in front of a larger group. At this point, tutors are oscillating between facilitating the discussion as different groups present their findings and providing direct instruction when explaining the meaning behind lab results/images, etc. Under the tutor’s guidance differential diagnoses are eliminated and the final diagnosis emerges. E: Lastly the tutor outlines treatment options. Due to time constraints, this was predominantly done in direct instruction

Recruitment and training of tutors

Tutors were recruited from the student body of those students who had completed the lecture on internal medicine and passed the exam. The recruitment process was based on Engel´s approach [ 17 ] and included a publicly shared application form and a job interview in which a shared decision was made on the topic best suited to the tutor´s interests and experience. A standardized curriculum was designed for tutors and delivered by a joint group of clinicians, the TUM Medical Education Center, and the organizing students who provided the impetus for ICCDs (Fig.  1 ). Mandatory training consisted of an introductory seminar on the ICCD´s didactic concept and a lecture on how to teach clinical reasoning skills and stimulate group interaction. Tutors then prepared their tutorial with their clinical supervisor as described above.

Questionnaire

Tutee evaluations were collected online at the end of each session using EvaSys V8.1 (evasys GmbH, Lueneburg, Germany). The survey comprised 50 self-report questions (supplementary material S2). Items were rated on a five-point Likert scale from 1 (strongly agree) to 5 (strongly disagree). For selected items, we also asked open-ended questions.

The underlying concept of the evaluation tool was modeled on the Student´s Evaluations of Educational Quality Questionnaire (SEEQ), a validated and reproducible evaluation tool proposed by Marsh in 1982 [ 29 ]. Designed for summative assessment of faculty-administered teaching, the SEEQ had to be adapted to our specific needs. We adopted evaluation items “I Learning/Value”, “IV Group Interaction” and all applicable items of “III Organisation” and “V Individual Raport”, yet omitted items VI-IX, since participation was completely voluntary, and examinations were not part of the ICCDs. Following the SEEQ category “I Learning/Value” we compared students´ subjective assessments of gain in knowledge, skill, motivation, and overall grade [ 30 ] after attending only the general lecture with attending both lecture and ICCD. We excluded SEEQ-section “II Enthusiasm” since tutors would have to proactively volunteer to teach in addition to their regular workload. Instead, we wanted to measure tutors´ performance as levels of cognitive congruence and educational environment. The tutor intervention profile by De Grave [ 31 ]and the Student Course Experience Questionnaire by Paul Ginns [ 32 ] reflected the aforementioned categories in more detail than the SEEQ and served as a reference. (Appendix Table 1 ). We also asked tutees to identify roles the tutor had assumed for them as proposed by Bulte et al. [ 21 ]. Learning outcomes were assessed as comparative self-assessment (CSA) for aggregated data [ 33 ]. The questions´ wording was based on the GESIS survey guidelines [ 34 ].

We handed tutors a short survey that asked them to rate the helpfulness of the introductory seminar, their understanding of the overall concept, and their difficulties in preparing the ICCD and enjoyment of the process on a five-point Likert scale.

Statistical analysis

We analyzed data using SPSS Statistics for Windows version 27 (IBM Corp., Armonk, New York, USA) and Microsoft Excel (Microsoft Corp., Redmond, Washington, USA). We included all surveys that had answers to more than 50% of all questions. If a student visited multiple sessions, only their first response to each question was included in the analysis. Learning outcomes and shifts in attitude toward peer teachers were computed as the CSA-gain as proposed by Raupach et al. (2011) [ 33 ]. Briefly, at the end of each session students were asked to retrospectively rate their expertise in the item before and after attending an ICCD session. The average net increase in self-assessment was then displayed as a percentage-wise increase over the average initial self-assessment. Qualitative, descriptive data were measured on a five-point Likert scale and analyzed using mean, mode, and standard deviation. Testing for statistical significance was performed using a two-tailed exact Chi-Square Test for categorical variables. Mann–Whitney-U-test was used for the comparison of metric variables with non-normal distribution between two groups (learning outcome). A p-value of 0.05 was chosen a priori. Effect size was calculated using Cramer´s V for descriptive data and correlations were computed using Spearman Correlation. Cronbach´s alpha was computed to test for internal consistency for the categories “cognitive congruence” and “educational environment”. Answers to open-ended questions were analyzed according to qualitative content analysis by Mayring [ 35 ]. Author JR developed the major categories deductively based on probable answers and supplemented them with subcategories inferred from students´ final responses. Another author, NS, checked categories for traceability. Finally, a category tree with specific anchor examples and defined subcategories emerged. The frequency of items and total number of student comments were recorded.

In the fall semester of 2020, a total of 335 students enrolled in the general lecture, 149 (44.5%) of whom attended at least one ICCD session. In the subsequent spring semester, 334 students enrolled in the general lecture and 237 (71.0%) took part in at least one ICCD session. Some tutees attended multiple sessions throughout the semesters. In sum, we counted 273 student attendances in the first and 521 in the second semester, respectively.

We received evaluations from 32.4% of all participants ( n  = 125). 91 (72.8%) tutees were aged 25 or under and 96 tutees (76.8%) identified as female. This approximately reflected the general student population (female/male: 65/35; mean age: 24 years). Questionnaires without informed consent were excluded from further analysis.

We employed 19 tutors for the implementation of 48 ICCD sessions covering a total of 24 topics. Eleven (57.8%) of those tutors identified as female and 12 (63.1%) had gained previous experience in front-line tertiary teaching.

Acceptance of ICCD

The nature of the ICCD being an add-on to the standard curriculum, we aimed to create additional value to the core curriculum that could not be attained with lectures and seminars alone. Evaluation of the ICCD shall therefore be displayed in direct comparison to the corresponding lecture (Fig.  3 ). ICCDs were generally rated as excellent and significantly better than lectures for all categories: knowledge, skill, attitude, and overall grade. Effect size was greatest for overall grade (V = 0.58; p  < 0.01) and smallest for gain in knowledge (V = 0.37; p  < 0.01) in ICCDs as opposed to the lecture. We observed that gain in knowledge correlated with gain in skills (r = 0.56; p  < 0.01) and overall evaluation of the ICCD session (r = 0.61; p  < 0.01).

Evaluation of ICCD vs. lecture. A Kiviat diagram representing students´ mean subjective assessment after attending lectures alone (round dots) and after attending both lectures and ICCD (long dashes) in categories knowledge, skill, attitude, and overall grade each represented on one of the axes of the diagram. Students were asked to rate their gain in each of the categories for both tutorial and the respective lecture on a five-point Likert scale with 1 denoting the greatest and 5 the lowest degree of satisfaction. Questionnaires were administered immediately after each tutorial. Tutorials took place one week after the general lecture. All differences are significant ( p  < .01). Effect size was calculated using Cramer´s V

When asked how comfortable tutees felt about being tutored by peers for an ICCD, tutees indicated a 70% increase in positive feelings after the intervention (CSA gain = 69.57%, n  = 111).

We received 57 answers to the open-ended questions on satisfaction and improvement suggestions (Table 1 ). In these answers, a total of 123 text segments (k) were identified and grouped into four categories. Most test segments praised the general format of the ICCD (k = 45). The second most frequent category included individual feedback on tutors (k = 40). The third category addressed learning value (k = 24) and the last category included improvement suggestions (k = 14).

Evaluation of Tutors

Mean cognitive congruence and educational environment for all sessions were rated as excellent at 1.26 ( n  = 121) and 1.35 ( n  = 107) respectively. Most tutees ascribed the roles “information provider” ( n  = 106, 84.4%) and “facilitator” ( n  = 87, 69.6%) to their tutors. Several tutees also rated their tutors as “role models” ( n  = 68,54.4%) and “assessors” ( n  = 51, 40.8%).

Learning outcome

CSA of learning outcomes revealed an increase in the ability to apply the correct diagnostic algorithm to a given case by 74.65% ( n  = 115). Ability to interpret the findings of diagnostic procedures increased by 70.31% ( n  = 114).

The end-of-course examination on internal medicine in the fall semester of 2020/21 consisted of 70 questions with a mean score of 85%. 30 (43%) questions have been previously discussed only during ICCD sessions, and 40 questions (57%) only during lectures. ICCD questions were answered with a higher score compared to lecture questions (90.3% vs. 82.4%, p  = 0.074). Although not statistically significant, students’ overall performance measured as a grade in the end-of-course examination was improved by material produced during ICCD sessions.

15 of 18 eligible tutors (83.33%) completed the survey. One tutor (author JR) conceived the questionnaire and was thus excluded to prevent potential bias.

Tutors rated the introductory seminar as helpful (mean 1.20) and indicated that the concept of the ICCD had been clearly communicated to them (mean 1.07). They did not report extreme difficulties conceiving a clinical case (mean 1.4) and indicated enjoying the process (mean 1.33).

This study aimed to report on an undergraduate students´ initiative to facilitate the core curriculum on internal medicine by developing and implementing the novel Integrated Clinical Case Discussions to train cognitive clinical skills relevant to the pertaining lecture. This information can help develop further student-led initiatives to address emergency remote teaching or other perceived curricular deficits with the expressed goal of training cognitive clinical skills.

The direct comparison of ICCDs and lectures versus emergency remote lectures alone revealed tutees´ subjective increased proficiency in clinical reasoning (determining diagnostic algorithm and interpreting findings). Similarly, students´ satisfaction levels rose. Tutees expressed positive feelings about being tutored by peers and high cognitive congruence.

We recorded increased participation rates in the second semester of ICCDs. The participation rate was 44.5% in the first and 71.0% in the second semester respectively. These participation rates merit special consideration, as the compulsory curriculum at TUM fulfils the legally required minimum number of classes and is supplemented with a broad range of voluntary courses (There are another 72 elective and extracurricular courses). This results in a competitive curricular environment in which students may be less intent on yet another learning opportunity, though the ICCDs are the only course covering the full spectrum of the lectures on internal medicine. The above-mentioned and increasing participation rates indicate that there is a target group that welcomes the offer of ICCDs, especially in the second semester on the cardiovascular and hematologic systems. We conclude, that a peer-moderated ICCD in response to emergency remote teaching can improve students´ subjective satisfaction level with learning opportunities and is in line with previous research [ 36 ]. Student satisfaction is important to consider, as it is one of the five pillars of Quality Online Education [ 37 ] and is positively correlated with student performance [ 38 ].

Our results support other studies highlighting the effectiveness of peer-teaching [ 39 , 40 ] and CCD [ 41 , 42 ] in teaching cognitive clinical skills. We found that students attending ICCDs in addition to the lecture benefitted from a gain in skill, overall satisfaction, motivation, and knowledge. This aligns with the ICCD´s goal of generating added value to the core curriculum.

Second, we conclude empowering students to organize and execute courses provides an effective way to create custom-tailored and widely accepted teaching formats. The excellent ratings of subjective learning outcomes, educational environment, and cognitive congruence support the notion that student leadership can be useful for curricular development [ 36 , 43 , 44 ].

We described the human and time resources for preparing one ICCD session. With student teachers contributing the most hours to an ICCD we are aware that additional teaching responsibilities might act as an additional stressor on tutors. However, our results suggest that tutors enjoy the process, feel well instructed and mentored in the workflow we proposed. Similarly, previous research has highlighted the benefits of being a peer teacher [ 10 , 45 ]. Furthermore, students who agree to tutor have been shown to have the necessary resources to cope with the additional stress at their command [ 46 ].

It has been repeatedly demonstrated that voluntary courses receive better feedback than compulsory courses [ 47 ]. This study was limited by the ICCD´s voluntary nature, too. Selection bias in the evaluation may be introduced by the self-selection of students who are highly motivated to attend an ICCD session on top of the lecture in comparison to those who attended the general lecture alone. The modest overall response rate of 32% also suggests that certain opinions are likely to be overrepresented while others may be missing. However, with the respondent demographics reflecting the general student population at TUM, we believe our study provides worthwhile data. Response rates of approximately 30% have been reported before in the context of voluntary peer teachings [ 21 ]. A study by Bahous et al. (2018) suggests that the reliability between voluntary questionnaires with a low response rate and compulsory questionnaires with a high response rate is comparable [ 48 ]. To allow for a more comprehensive interpretation of results we also reported the maximum number of possible and de-facto attendances as demonstrated earlier [ 33 ]. The study design does not allow for a follow-up to assess the long-term impact on knowledge, skill, and attitude. Since our findings are based on data from one medical school in Germany they cannot be extrapolated to other medical schools without further consideration. However, the German model of medical education being common in Europe, we have reason to believe that study populations at other medical schools may be similar and our findings of value to their curricular designers [ 49 ].

Empowering students to design their own add-on learning opportunities can improve learning outcomes, teach clinical reasoning skills beyond the scope of the core curriculum and increase satisfaction ratings with learning opportunities. We believe that our concept provides an easy-to-implement and up-scalable format to alleviate pressure on faculty staff and physicians with teaching capabilities for other schools, too.

For future optimization, we propose to advance the beneficial effect of social and cognitive congruence by inviting lecturers to facilitate ICCD sessions in person as we are now planning at TUM for the fall semester of 2022/23. This ultimately leads to a triangularized teaching format in which a student-tutor moderates the discussion, lecturers support discussions with more in depth-knowledge and clinical experience, and tutees engage in an instructive discussion.

Availability of data and materials

The datasets during and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Abbreviations

Severe Acute Respiratory Syndrome Coronavirus Type 2

Technical University of Munich

Peer-assisted learning

Integrated Clinical Case Discussion

German Medical Training Framework

Clinical Case Discussion

Student´s Evaluations of Educational Quality Questionnaire

Comparative Self Assessment

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Acknowledgements

We would like to thank all our tutors for their outstanding engagement and continuous feedback on improving ICCD as well as all the people who have provided useful productive feedback on earlier manuscripts. We would particularly like to thank the reviewers of this article for their encouragement and highly detailed feedback.

Open Access funding enabled and organized by Projekt DEAL. This work was kindly supported by the Technical University of Munich under a grant for teaching-related projects of excellence at Technical University of Munich (TUM) (“Studienbezogene Exzellenstrategie der TUM”) and partly under a fund jointly handled by student representatives and the TUM Medical Education Center (“Planungsmittelkommission”).

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Johannes Reifenrath, Nick Seiferth, Theresa Wilhelm, Christopher Holzmann-Littig & Marjo Wijnen-Meijer

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Christopher Holzmann-Littig

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Contributions

JR conceived the didactic concept of the ICCD, developed the questionnaire, and oversaw the data acquisition. NS was chief exchequer, head of human resources, and coordinated cooperation with the lecturers. TW developed administered the online material, zoom-links, and monitored student commentaries for continuous improvement. CHL helped with conceiving the evaluation tool and data analysis. VP matched lecturers to the ICCD sessions, facilitated their communication with the tutors, and majorly revised the manuscript. MWM conducted the didactic lecture and majorly revised the manuscript. All authors have read and approved the manuscript.

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At the time of the study the following statements apply:

Johannes Reifenrath is a fifth-year medical student at Technical University of Munich, School of Medicine, and a student representative to the school´s committee on curricular development.

Nick Luca Seiferth is a fifth-year medical student at Technical University of Munich, School of Medicine, and a student envoy to the school´s faculty council.

Theresa Wilhelm is a sixth-year medical student at Technical University of Munich, School of Medicine, and a student representative to the school´s committee on curricular development.

Christopher Holzmann-Littig, MD, is a resident at Technical 482 University, School of Medicine, Department of Nephrology, and a 483 member of TUM Medical Education Center.483 member of TUM Medical Education Center.

Veit Phillip, MD, Instructor of Medicine, is a senior physician at Technical University, School of Medicine, Department of Gastroenterology and coordinates the lectures on internal medicine.

Marjo Wijnen-Meijer is head of innovation at the TUM Medical Education Center and specializes in curricular development.

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Appendix Table 1. Cognitive Congruence and Educational Environment. The table gives an overview of the items used to compute the cognitive congruence between tutors and tutees using the mean of section “1. Cognitive Congruence”, where 1 denotes the greatest and 5 the lowest level of tutees´ satisfaction. Tutees´ perception of the educational environment was computed by calculating the mean of the items in section “2. Educational Environment”. Cronbach´s alpha for cognitive congruence was 0.76; for educational environment 0.83.

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Reifenrath, J., Seiferth, N., Wilhelm, T. et al. Integrated clinical case discussions – a fully student-organized peer-teaching program on internal medicine. BMC Med Educ 22 , 828 (2022). https://doi.org/10.1186/s12909-022-03889-4

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Educational Case: Acute Cystitis

Ryan l. frazier.

1 Department of Pathology, School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. Huppmann is now at the University of South Carolina School of Medicine Greenville, Greenville, SC, USA.

Alison R. Huppmann

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040 . 1

Primary Objective

Objective UTB2.1 : Acute Cystitis . Discuss the typical clinical symptomatology of acute cystitis and the organisms commonly causing this disorder.

Competency 2 Organ System Pathology; Topic UTB: Bladder; Learning Goal 2: Bladder Infection.

Secondary Objectives

Objective M2.11: Urine Studies for Cystitis . Explain the role of urine studies, including culture, in selecting antimicrobial therapy for infectious cystitis.

Competency 3 Diagnostic Medicine and Therapeutic Pathology; Topic M: Microbiology; Learning Goal 2: Antimicrobials.

Objective M2.12: Diagnosis of UTI . Describe a testing strategy for a typical uncomplicated community acquired urinary tract infection (UTI) versus a nosocomial UTI in a patient with a Foley catheter and list the key microbiological tests in diagnosis of UTIs.

Patient Presentation

A 27-year-old woman presents to her primary care physician with a report of urinating more frequently and pain with urination. She denies blood in her urine, fevers, chills, flank pain, and vaginal discharge. She reports having experienced similar symptoms a few years ago and that they went away after a course of antibiotics. The patient has no other past medical problems. Pertinent history reveals she has been sexually active with her boyfriend for the past 4 months and uses condoms for contraception. She reports 2 lifetime partners and no past pregnancies or sexually transmitted diseases. Her last menstrual period was 1 week ago.

Diagnostic Findings, Part 1

On physical exam, the patient is afebrile, normotensive, and non-tachycardic. She appears well on observation. She has a soft, nondistended abdomen with normoactive bowel sounds. On palpation, she has moderate discomfort in her suprapubic region but no costovertebral angle (CVA) tenderness. A pelvic exam is normal with no evidence of abnormal vaginal or cervical discharge or inflammation.

Questions/Discussion Points, Part 1

What is the differential diagnosis for this patient which diagnosis is most likely and why.

The top entities in the differential diagnosis include a UTI, vaginitis/cervicitis, and pyelonephritis. The most likely diagnosis in this patient is a UTI, specifically, acute cystitis. Classic UTI symptoms include urinary frequency and urgency and dysuria. Other complaints could include suprapubic pain or discomfort, hesitancy, nocturia, and even gross hematuria. Urinary tract infections are classified by the anatomical location in which the infection and inflammation occur. Risk factors that this patient possesses, which will be discussed later, are female sex, age, recent sexual activity, and a history of prior UTI, which we can infer from her report of previous similar symptoms. 2

Vaginitis and cervicitis should also be considered in this patient given her history of sexual activity. However, the patient has no reported vaginal discharge or signs of these infections on pelvic examination. Another important diagnosis to consider is pyelonephritis, which involves infection of the upper urinary tract. This is also not likely given her lack of fever, flank pain, and other key symptoms which will be discussed in a later section.

Is Laboratory Testing Required To Confirm the Diagnosis in This Patient?

Laboratory studies are not needed in this patient due to the high likelihood of a UTI, and empirical treatment can be administered. Thus, the importance of a good history and physical exam is highly emphasized when caring for a patient with a possible UTI. Uncomplicated UTIs are commonly observed and treated in the outpatient setting; they are increasingly being diagnosed without an in-person visit via telephone. 2

Which Populations Are at Higher Risk of Contracting a UTI? Why? Discuss the Terms “Uncomplicated UTI” Versus “Complicated UTI”

Urinary tract infections are due to the colonization of the urinary tract by microbes. Certain populations are at higher risk of infections of the urinary tract. Women are among those most affected by UTIs, with a lifetime incidence rate of almost 50%. 3 The difference between the sexes is attributed to women’s shorter urethral length. Women who are sexually active are also at risk of UTI due to the proximity of the urethral meatus to the flora-rich anus. If the patient is a premenopausal, otherwise healthy, and nongravid female, as in this case, she has developed an “uncomplicated” infection. 2 , 4

Patients who are predisposed to conditions that make colonization more likely or are exposed to microbes that are more facile in evading the body’s natural protective mechanisms are more apt to contract UTIs, and their infections can be more difficult to treat. These patients have “complicated” infections. Numerous conditions make a patient more susceptible to UTI. These include underlying medical problems or structural abnormalities of the urinary tract such as urinary obstruction, vesicoureteral reflux, underlying urinary tract disease, diabetes, renal papillary necrosis, immunosuppression (medically induced or as a result of HIV infection), treatment with antibiotics, pregnancy, menopause, and spinal cord injuries. 4 The elderly are also at increased risk of UTI, particularly men, many of whom develop obstructive uropathy from benign prostatic hypertrophy. 2 , 4

When Should a Diagnosis of Pyelonephritis Be Suspected?

Infection of the kidney is termed pyelonephritis. These patients tend to present acutely with “upper tract signs,” to include fever, chills, flank pain, and CVA tenderness. Symptoms of lower UTI can also be present; however, this is not usually the case. The clinical presentation may vary and can be life-threatening. In the most severely ill, patients may present in septic shock, with hypotension, tachycardia, and tachypnea, especially when infected with a gram-negative organism. 4

Which Laboratory Studies Can Be Performed on Urine To Evaluate a Potential UTI? What Is the Diagnostic Value of Each Test?

Laboratory tools are commonly utilized in the investigation of UTIs for patients with a complicated UTI, recurrent infections, or an unclear diagnosis based purely on history and physical exam. Again, test results should always be correlated with clinical findings, as false-positive or false-negative results can occur through multiple avenues. Available tests include a urine dipstick, urinalysis with microscopy, and culture and gram stain with sensitivity testing. The first 2 of these have the potential to be performed in physicians’ offices. A clean-catch midstream specimen should be submitted to avoid contamination from vaginal or penile microorganisms. Patients should be given a 2% castile soap towelette and instructed in appropriate specimen collection. Men should cleanse the glans, retracting the foreskin first if uncircumcised. Women should cleanse the periurethral area after spreading the labia. Identification of lactobacilli and epithelial cells from the vagina suggest contamination. 4

General features of the urine can first be examined to include the color, clarity, and odor; but these features are nonspecific. For example, cloudy urine can be caused by the presence of white blood cells and/or bacteria in a UTI; but it can also be caused by numerous other pathologic and non-pathologic substances.

Urine dipstick studies, primarily searching for leukocyte esterase and nitrites, are useful when the pretest probability of UTI is high. Leukocyte esterase is an enzyme possessed by white blood cells. Thus, a positive urine dipstick for leukocyte esterase indicates the presence of inflammatory cells in the patient’s urinary tract. Inflammatory cells in the urine are not specific for a UTI, as leukocytes can also be present in other situations such as glomerulonephritis and vaginal contamination. Nitrite is a breakdown product of nitrates, which are normally found in a healthy patient’s urine. The dipstick test for nitrite is specific for gram-negative organisms which possess an enzyme enabling them to reduce nitrates. It follows, then, that this test is less useful in the setting of potential gram-positive microbe infection. Also notable is that the nitrite test can be falsely negative in a patient with abundant fluid intake and frequent urination. 2 Multiple other factors including medications, diet, and specimen handling can affect urine dipstick results, as can inappropriate handling or expiration of test strips.

Urinalysis with microscopy provides a window into the kidney and urinary tract. The presence of red blood cells, white blood cells, casts, crystals, and bacteria aid in many diagnoses. Specific to UTI, the presence of white blood cells and red blood cells indicates inflammation and, potentially, infection in the urinary tract. 2 Pyuria, the presence of leukocytes in the urine, is not specific to UTIs as noted above; but the absence of leukocytes should cause one to question a diagnosis of UTI unless the culture is positive. The identification of crystals might suggest the presence of renal calculi, which can serve as a nidus for infection. In fact, some stones (eg, struvite) are the direct result of infection with urea-splitting organisms. Overall, urinalysis is useful; however, the clinical history still plays a key role to avoid under- and overdiagnosis. 4

Urine culture is the gold standard diagnostic tool for diagnosing UTIs. 2 , 4 As stated previously, in patients with a convincing clinical history and physical exam consistent with uncomplicated cystitis, no culture is necessary. However, in patients with complicated, severe upper urinary tract, or recurrent UTIs, urine culture should not be foregone, as it is necessary for determining the causative organism and, consequently, for guiding appropriate therapeutic intervention. Furthermore, growth of the organism in culture facilitates sensitivity studies, in which pharmacologic agents are tested on the microbe isolated from the patient. This testing provides medical personnel with information regarding the efficacy of potential therapeutic options in the form of minimal inhibitory concentrations. This information guides narrowing of antibiotic choice from whichever broad-spectrum treatment was initiated when a UTI was first suspected. 2 Some organisms such as Ureaplasma urealyticum may not be grown on routine cultures, so a false-negative result is possible. False-positive results are rare, other than due to contamination, which should be suspected in most cases with growth of multiple types of bacteria or vaginal flora. 4

What Is Asymptomatic Bacteriuria?

The diagnosis of asymptomatic bacteriuria requires 2 criteria: (1) The urine is culture-positive and (2) the patient does not have symptoms or signs of a UTI. The level of bacteria in culture should reach ≥10 5 CFU/mL, although it can be lower in catheterized patients (≥10 2 CFU/mL). Asymptomatic bacteriuria is only treated in some groups of patients, including those who are pregnant or undergoing urologic procedures, as it otherwise does not correlate with symptomatic disease or complications. 2

Which Microorganisms Most Commonly Cause Acute Cystitis?

In general, gram-negative aerobic rods are the most commonly isolated pathogens implicated in UTIs. 2 Escherichia coli is the most common causative organism of UTIs, especially in sexually active young women. 2 , 4 Microorganisms such as uropathogenic E coli (UPEC) with an enhanced ability to bind and to adhere to urinary tract epithelia are more capable of causing infection. Adhesins and pili resistant to the innate immune mechanisms of defense are among the advantageous traits that particularly virulent strains of UPEC possess. 4

A variety of other Enterobacteriaceae (discussed below) are also found in the setting of catheter-associated UTIs (CAUTIs). However, gram-positive organisms are clinically significant in some settings. Staphylococcus saprophyticus is not infrequently implicated in uncomplicated UTIs in young, sexually active women. 2 Group B Streptococcus (GBS, Streptococcus agalactiae ) is of particular concern in pregnant patients. In 1 prospective study, GBS was the second most isolated pathogen behind E coli in the urine of asymptomatic bacteriuric pregnant women. 5 Screening pregnant women for asymptomatic bacteriuria plays an important role in decreasing the risk of pyelonephritis during pregnancy. 6 , 7 Table 1 summarizes the typical microorganisms identified in complicated and uncomplicated UTIs along with the appropriate laboratory testing.

Common Causative Organisms and Indicated Laboratory Tests for Patients With Uncomplicated and Complicated Urinary Tract Infections (UTIs).

Abbreviation: STI, sexually transmitted infection.

Discuss CAUTIs and Their Difference From Non-CAUTIs, Including Clinical Features and Causative Microorganisms

Per the Infectious Diseases Society of America, 8 both clinical and laboratory criteria should be met to make the diagnosis of a catheter-associated UTI (CAUTI). The patient should have signs or symptoms of a UTI and no other known source of infection. Culture of the patient’s urine sample should yield greater than 10 3 colony-forming units (CFU)/mL of at least 1 species of bacteria. The cultured urine should be from a single specimen in those patients who are still catheterized. Catheter-associated UTI can also be diagnosed in those whom have had a catheter removed within the preceding 48 hours, in which case a midstream voided urine is the appropriate specimen.

Catheter-associated UTIs are a type of complicated UTI and are among the most common nosocomial (hospital-acquired) infections in the United States. 4 Urinary catheters facilitate the ascent of microbes into the urinary tract. There are different methods of catheterization, for example, clean intermittent catheterization, indwelling urethral catheters, and suprapubic catheters. Microorganisms can be introduced during the procedure of catheterization despite the implementation of sterilization methods. Also, without appropriate catheter care, these indwelling devices can become a nidus for infection, permitting various other flora to travel along the tube and into the urinary tract. 4

As previously mentioned, E coli is the most common causative organism of acute cystitis in uncomplicated UTIs. 4 It is also the most commonly isolated organism in CAUTI. 8 , 9 However, patients with catheters are at higher risk of infection by organisms less commonly seen in non-catheterized patients. Patients who are catheterized for both short and long periods of time are at increased risk of infection with fungal organisms as well as Enterobacteriaceae such as Klebsiella , Serratia , Enterobacter , Pseudomonas , Enterococcus , and Proteus species. 4 , 6 , 9 These organisms are exceptionally well-adapted for invasion given the ability many of them possess to form biofilms. The longer a patient is catheterized, the more likely they are to develop bacteriuria, a symptomatic infection, and potentially colonization of the urinary tract. 4 Thus, timely removal of catheters when no longer necessary is wise.

How Should Patients With UTIs Be Treated?

The choice of therapy for UTIs depends on the clinical treatment setting, and whether it is a complicated or uncomplicated UTI. An optimal outpatient antibiotic can be taken orally, has a tolerable side effect profile, and is concentrated to a therapeutic level in the patient’s urine. 4 Antibiotics that fit this profile are appropriate to give patients who have a low risk for infection with a multidrug resistant strain. Options for therapy include nitrofurantoin monohydrate, trimethoprim-sulfamethoxazole, fosfomycin, and pivmecillinam. 4 , 10

Recent infectious disease guidelines reflect growing concern for infection with multidrug resistant organisms. 10 When therapy needs to be escalated due to infection with a multidrug resistant organism or tissue-invasive disease with bacteremia, options remain for oral therapy. In these situations, it is advantageous to obtain urine culture and microbe antibiotic sensitivities to better eliminate the infection. If hospitalization is indicated and the patient requires parenteral antibiotics, empiric therapy should be initiated. After microorganism sensitivities return, antibiotic therapy can be narrowed to one of the following: a carbapenem, third-generation cephalosporin, fluoroquinolone, ampicillin, and gentamicin. 4

Pharmacotherapy for complicated UTIs should begin with broad-spectrum therapy and then be narrowed by sensitivities when possible. 4 The grouping which places the patient in the “complicated” category plays a role in treatment selection. For example, UTIs in men typically involve the prostate as well as the bladder, so treatment should target the infection in both organs. Patients who are pregnant require antibiotics that are safe for the fetus. 2 Some complicated UTIs, especially in the case of upper UTIs, are managed inpatient with intravenous antibiotics due to the presence of tissue-invasive disease or bacteremia. In this case, the concentration of antibiotic in the blood and the urine are important. This differs from the treatment of uncomplicated UTIs, which are dependent on the concentration of the pharmacotherapeutic agent in the urine. 4

Potential correction of modifiable risk factors for UTIs, if present, can also be addressed to prevent recurrent infection. This may include correction of an anatomic or structural abnormality of the urinary tract, consideration of alternative birth control types in a woman who uses a diaphragm with spermicide, removing a urinary catheter, or simply counseling a woman to attempt urination after sexual intercourse.

Describe Potential Complications of UTIs

Urinary tract infections can be complicated by several conditions depending on the severity and chronicity of the infection and the implicated organism. Severe upper UTIs can lead to acute kidney injury and, if not treated, can lead to permanent kidney damage and fibrosis. Similarly, upper UTIs can be complicated by renal or perinephric abscess(es). Renal abscesses are most found in patients with preexisting kidney disease. Patients infected by a urea-splitting organism are at risk of struvite stones, which are commonly found in the upper urinary tract. 4

Teaching Points

• Acute cystitis is a form of UTI and commonly presents with urinary frequency, urgency, and dysuria. Uncomplicated cases of UTIs, those seen in otherwise young, healthy, adult women, can be diagnosed by a thorough history and physical exam.
• Urinary tract infections are most often seen in sexually active, young women and older men with benign prostatic hyperplasia.
• Escherichia coli is the most implicated organism in UTIs. Other aerobic gram-negative rods and sometimes gram-positive microorganisms can be implicated, especially in patients with preexisting conditions or indwelling urinary catheters.
• Laboratory investigations, including dipstick tests, urinalysis, and urine culture, can aid physicians in the diagnosis of UTIs when needed and are important to guide effective treatment, especially in complicated UTIs.
• Uncomplicated UTIs can bet treated with outpatient oral antibiotics, with choices to include nitrofurantoin monohydrate, trimethoprim-sulfamethoxazole, fosfomycin, and pivmecillinam.
• Complicated UTIs occur in patients at higher risk of infection or in whom the infection may be difficult to treat. Some examples of patients in this category include those with anatomic or other urinary tract obstruction, catheter-associated UTIs, pregnant women, and patients who are immunosuppressed.
• Pyelonephritis is a serious upper UTI which can potentially be life-threatening if not treated promptly.
• Complications of UTIs include renal abscesses, acute kidney injury leading to chronic kidney disease, and struvite calculi.
• Broad-spectrum pharmacotherapy should be initiated for complicated microbial infections of the urinary tract. After sensitivity studies from the patient’s urine return, treatment can be narrowed to avoid the development of multi-drug resistant organisms.

Author’s Note: The opinions expressed herein are those of the author and are not necessarily representative of those of the Uniformed Services University of the Health Sciences (USUHS), the Department of Defense (DOD), or the United States Army, Navy, or Air Force.

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding: The author(s) received no financial support for the research, authorship, and/or publication of this article.

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Research on intercity railway subsidy mechanism optimization from the perspective of a government–company game model: a case study of henan intercity railway.

1. Introduction

2. literature review, 2.1. research on the optimization of the railway subsidy mechanism, 2.2. research on game and subsidy mechanism optimization, 2.3. summary, 3. materials and methods, 3.1. problem description, 3.2. model assumption, 3.3. performance subsidy, 3.4. model framework, 3.5. calculation of expected payoff, 3.6. expected payoff of governments, 3.7. expected payoff of railway companies, 3.8. expected payoff of social capitals, 3.9. conclusion and simplification, 4. results and discussion, 4.1. background, 4.2. simulation results without performance subsidy, 4.3. simulation results with performance subsidy, 4.4. sensitivity analysis and discussion, 5. conclusions and policy suggestion, 5.1. conclusions, 5.2. policy suggestions, author contributions, institutional review board statement, informed consent statement, data availability statement, acknowledgments, conflicts of interest.

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Yue, G.; Zhao, Z.; Dai, L.; Hu, H. Research on Intercity Railway Subsidy Mechanism Optimization from the Perspective of a Government–Company Game Model: A Case Study of Henan Intercity Railway. Sustainability 2024 , 16 , 7631. https://doi.org/10.3390/su16177631

Yue G, Zhao Z, Dai L, Hu H. Research on Intercity Railway Subsidy Mechanism Optimization from the Perspective of a Government–Company Game Model: A Case Study of Henan Intercity Railway. Sustainability . 2024; 16(17):7631. https://doi.org/10.3390/su16177631

Yue, Guoyong, Zijian Zhao, Lei Dai, and Hao Hu. 2024. "Research on Intercity Railway Subsidy Mechanism Optimization from the Perspective of a Government–Company Game Model: A Case Study of Henan Intercity Railway" Sustainability 16, no. 17: 7631. https://doi.org/10.3390/su16177631

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