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Female genital mutilation is widely recognised as a practice that causes grave, permanent damage to the genital anatomy and function. The literature has documented its impact on physical, sexual, emotional, and mental wellbeing, and this has informed the development of guidelines and recommendations for managing women with female genital mutilation. There has, though, been little, if any, focus on how women with female genital mutilation experience menopause. A literature search did not return any published research on the topic and there are currently no clinical guidelines for managing the menopause in women who have undergone female genital mutilation. This review calls attention to this gap by exploring the clinical implications that the loss of natural hormones has on the vulvovaginal tissues, as well as on urogenital and sexual function. Psychological aspects of the experience of women with female genital mutilation going through menopause are also explored, as well as common barriers they face in accessing adequate healthcare. Finally, we offer a set of recommendations for clinical practice, including the need to improve current care pathways, and potential directions for future research.
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Circuncisión Femenina , Menopausia , Humanos , Femenino , Circuncisión Femenina/psicología , Circuncisión Femenina/efectos adversos , Menopausia/psicología , Menopausia/fisiología , Accesibilidad a los Servicios de Salud , Necesidades y Demandas de Servicios de SaludRESUMEN
In this second episode of the Microbiologist in the Clinic series, clinicians and laboratory scientists share their perspectives about a 75-year-old woman who was diagnosed with asymptomatic bacteriuria based on positive urine cultures. The patient and her GP are concerned about this laboratory finding as the patient will become immunosuppressed with planned chemotherapy. The patient has had an overactive bladder (OAB) for approximately 20 years, with good control of her urinary urgency and frequency (no incontinence) with a stable dose of OAB medication. The challenges of this clinical presentation are discussed, with evidence for evaluation and treatment.
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Urinary tract infection (UTI) is a common disorder. Its diagnosis can be made by microscopic examination of voided urine for markers of infection. This manual technique is technically difficult, time-consuming and prone to inter-observer errors. The application of computer vision to this domain has been slow due to the lack of a clinical image dataset from UTI patients. We present an open dataset containing 300 images and 3,562 manually annotated urinary cells labelled into seven classes of clinically significant cell types. It is an enriched dataset acquired from the unstained and untreated urine of patients with symptomatic UTI using a simple imaging system. We demonstrate that this dataset can be used to train a Patch U-Net, a novel deep learning architecture with a random patch generator to recognise urinary cells. Our hope is, with this dataset, UTI diagnosis will be made possible in nearly all clinical settings by using a simple imaging system which leverages advanced machine learning techniques.
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Aprendizaje Profundo , Infecciones Urinarias , Humanos , Pruebas Diagnósticas de Rutina , Aprendizaje Automático , Microscopía , Infecciones Urinarias/diagnóstico , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/orinaRESUMEN
In this first episode of the Microbiologist in the Clinic series, clinicians and laboratory scientists share their perspectives about a 30 y/o woman, who is seeking specialty consultation for frequent episodes of urinary urgency, frequency, and dysuria, which respond to short courses of antibiotics. Although her home dipsticks suggest that she has a UTI, and her urinalysis typically has a moderate number of white blood cells, her urine cultures are always negative. The challenges of this clinical presentation are discussed with evidence for evaluation and treatment.
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Infecciones Urinarias , Trastornos Urinarios , Humanos , Femenino , Infecciones Urinarias/diagnóstico , Infecciones Urinarias/tratamiento farmacológico , Urinálisis , Antibacterianos/uso terapéutico , Disuria , OrinaRESUMEN
Urinary tract infections (UTIs) exert a significant health and economic cost globally. Approximately one in four people with a previous history of UTI continue to develop recurrent or chronic infections. Research on UTI has primarily concentrated on pathogen behavior, with the focus gradually shifting to encompass the host immune response. However, these are centered on mouse models of Escherichia coli infection, which may not fully recapitulate the infective etiology and immune responses seen in humans. The emerging field of the urobiome also inadvertently confounds the discrimination of true UTI-causing pathogens from commensals. This review aims to present a novel perspective on chronic UTI by linking microbiology with immunology, which is commonly divergent in this field of research. It also describes the challenges in understanding chronic UTI pathogenesis and the human bladder immune response, largely conjectured from murine studies. Lastly, it outlines the shortcomings of current diagnostic methods in identifying individuals with chronic UTI and consequently treating them, potentially aggravating their disease due to mismanagement of prior episodes. This discourse highlights the need to consider these knowledge gaps and encourages more relevant studies of UTIs in humans.
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Infecciones por Escherichia coli , Infecciones Urinarias , Humanos , Animales , Ratones , Inmunidad Mucosa , Infecciones por Escherichia coli/microbiología , Bacterias , Vejiga UrinariaRESUMEN
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causing the COVID-19 pandemic, has had an enormous effect on conventional clinical practice. Telemedicine has emerged as critical to the provision of healthcare services when reducing the transmission of COVID-19 among patients, families, and clinicians. It has been an essential tool for continuing care for patients with lower urinary tract symptoms (LUTS) during the COVID-19 pandemic and has been the link between socially distant patient contact. The aim of this perspective paper was to identify the strengths and limitations of technology-based care focusing on literature linked to patients with lower urinary tract symptoms (LUTS). We search PubMed and CINHAL Plus for grey literature and secondary research on LUTS and telemedicine during the COVID-19 pandemic. Publications dated between the year March 2020 and March 2021were searched. We gathered key specialist opinions in the field of LUTS from several countries around the world, including the countries that had been hit significantly with COVID-19. This perspective paper proposes that there is evidence to support the use of modern technology to facilitate continued healthcare services for patients with LUTS during the COVID-19 pandemic. Telemedicine has been recognised a crucial digital tool for diagnosis, treatment and follow-up appointments during a time of social distancing. Although there are many advantages of telemedicine, the older adult population and those economically disadvantaged with technology may not benefit from technology-based healthcare. The available literature on telemedicine during the COVID-19 pandemic has proven to be successful in the management of some patients with LUTS. It is certain that the COVID-19 pandemic has given telemedicine a significant drive for implementation now and in the immediate future. Robust data on long-term efficacy and safety of telemedicine is required to ensure there are governance protocols embedded when looking after patients with LUTS.
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BACKGROUND: Contemporary studies have discredited the methods used to exclude urinary tract infection (UTI) when treating overactive bladder (OAB). Thus we must revisit the OAB phenotype to check that UTI has not been overlooked. AIMS: To examine the differences in urinary cytokines IL6 and lactoferrin in OAB patients compared to controls, with references to microscopy of urine and enhanced quantitative urine culture. METHODS: A blinded, prospective cohort study with normal controls using six repeated measures, achieved two-monthly, over 12 months. RESULTS: The differences between patients and controls in urine IL6 (F = 49.0, p < .001) and lactoferrin (F = 228.5, p < .001) were significant and of a magnitude to have clinical implications. These differences were for lactoferrin correlated to symptoms (9.3, p = .003); for both to pyuria (IL6 F = 66.2, p < .001, Lactoferrin F = 73.9, p < .001); and for IL6 microbial abundance (F = 5.1, p = .024). The pathological markers had been missed by urinary dipsticks and routine MSU culture. CONCLUSION: The OAB phenotype may encompass patients with UTI that is being overlooked because of the failure of standard screening methods.
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Interleucina-6/orina , Lactoferrina/orina , Vejiga Urinaria Hiperactiva/orina , Anciano , Femenino , Humanos , Inflamación/etiología , Inflamación/orina , Persona de Mediana Edad , Estudios Prospectivos , Método Simple Ciego , Vejiga Urinaria Hiperactiva/complicacionesRESUMEN
PURPOSE: To measure the effects of an unplanned, sudden cessation of treatment in an unselected group of patients with chronic painful LUTS managed with protracted antimicrobial treatment and to report these observational data collected from a cross-over process. MATERIALS AND METHODS: The imposition of a guideline resulted in the immediate cessation of antibiotic treatment in a cohort of patients with chronic painful LUTS and microscopic pyuria. Patients were assessed before treatment withdrawal, whilst off treatment, and following reinstatement. Outcome measures included a validated symptom score, microscopic enumeration of urinary white cells and uroepithelial cells, and routine urine culture. RESULTS: These patients had reported treatment-resistant, painful LUTS for a mean of 6.5 years before treatment at this centre. Treatment was stopped in 221 patients (female = 210; male = 11; mean age = 56 years; SD = 17.81). Sixty-six per cent of women were post-menopausal. After unplanned treatment cessation, 199 patients (90%; female = 188; male = 9) reported deterioration. Eleven patients required hospital care in association with disease recurrence, including acute urinary tract infection (UTI) and urosepsis. Symptom scores increased after cessation and recovered on reinitiating treatment (F = 33; df = 2; p < 0.001). Urinary leucocyte (F = 3.7; df = 2; p = 0.026) and urothelial cells counts mirrored symptomatic changes (F = 6.0; df = 2; p = 0.003). Routine urine culture results did not reflect changes in disease status. CONCLUSION: These data support the hypothesis that treating painful LUTS associated with pyuria with long-term antimicrobial courses, despite negative urine culture, is effective. The microscopy of fresh unspun, unstained urine to count white cells and epithelial cells offers a valid method of monitoring disease. An unplanned cessation of antibiotic therapy produced a resurgence of symptoms and lower urinary tract inflammation in patients with chronic LUTS, supporting an infective aetiology below the level of routine detection.
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Antibacterianos/uso terapéutico , Síntomas del Sistema Urinario Inferior/tratamiento farmacológico , Nitrofurantoína/uso terapéutico , Infecciones Urinarias/tratamiento farmacológico , Privación de Tratamiento , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/administración & dosificación , Enfermedad Crónica , Estudios Cruzados , Femenino , Humanos , Recuento de Leucocitos , Síntomas del Sistema Urinario Inferior/etiología , Masculino , Persona de Mediana Edad , Nitrofurantoína/administración & dosificación , Dolor/tratamiento farmacológico , Dolor/etiología , Piuria/complicaciones , Piuria/tratamiento farmacológico , Piuria/orina , Recurrencia , Retratamiento , Evaluación de Síntomas , Infecciones Urinarias/complicaciones , Adulto JovenRESUMEN
Midstream urine (MSU) culture remains the gold standard diagnostic test for confirming urinary tract infection (UTI). We previously showed that patients with chronic lower urinary tract symptoms (LUTS) below the diagnostic cutoff on MSU culture may still harbor bacterial infection and that their antibiotic treatment was associated with symptom resolution. Here, we evaluated the results of the United Kingdom's MSU culture in symptomatic patients and controls. Next, we compared the bacterial enrichment capabilities of the MSU culture with those of a 50-µl uncentrifuged culture, a 30-ml centrifuged sediment culture, and 16S rRNA gene sequencing. This study was conducted on urine specimens from 33 LUTS patients attending their first clinical appointment (mean age, 48.7 years; standard deviation [SD], 16.5 years), 30 LUTS patients on treatment (mean age, 47.8 years; SD, 16.5 years) whose symptoms had relapsed, and 29 asymptomatic controls (mean age, 40.7 years, SD, 15.7 years). We showed that the routine MSU culture, adopting the UK interpretation criteria tailored to acute UTI, failed to detect a variety of bacterial species, including recognized uropathogens. Moreover, the diagnostic MSU culture was unable to discriminate between patients and controls. In contrast, genomic analysis of urine enriched by centrifugation discriminated between the groups, generating a more accurate understanding of species richness. In conclusion, the United Kingdom's MSU protocol misses a significant proportion of bacteria, which include recognized uropathogens, and may be unsuitable for excluding UTI in patients with LUTS.
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Técnicas Bacteriológicas/métodos , Urinálisis/métodos , Infecciones Urinarias/diagnóstico , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infecciones Urinarias/microbiología , Infecciones Urinarias/orina , Adulto JovenRESUMEN
PURPOSE: Lower urinary tract symptoms (LUTS) may be associated with chronic urinary tract infection (UTI) undetected by routine diagnostic tests. Antimicrobial therapy might confer benefit for these patients. MATERIALS AND METHODS: Over 10 years, we treated patients with chronic LUTS. Pyuria was adopted as the principal biomarker of infection. Urinary leucocyte counts were recorded from microscopy of fresh midstream urine (MSU) samples. Antibiotics were prescribed and the prescription adjusted to achieve a measurable clinical response and a reduction in pyuria. RESULTS: We treated 624 women [mean age = 53.4 years; standard deviation (SD) = 18] with chronic LUTS and pyuria. Mean duration of symptoms prior to presentation was 6.5 years. Only 16% of MSU cultures submitted were positive (≥105 cfu ml-1). Mean treatment length was 383 days [SD = 347; 95% confidence interval (CI) = 337-428]. Treatment was associated with a reduction in total LUTS (F = 98; p = 0.0001), 24-h frequency (F = 75; p = 0.0001), urinary urgency (F = 90; p = 0.0001), lower urinary tract pain (F = 108; p = 0.0001), voiding symptoms (F = 10; p = 0.002), and pyuria (F = 15.4; p = 0.0001). Full-dose first-generation antibiotics for UTI, such as cefalexin, nitrofurantoin, or trimethoprim, were combined with methenamine hippurate. We recorded 475 adverse events (AEs) during 273,762 treatment days. There was only one serious adverse event (SAE). We observed no increase in the proportion of resistant bacterial isolates. CONCLUSION: This large case series demonstrates that patients with chronic LUTS and pyuria experience symptom regression and a reduction in urinary tract inflammation associated with antimicrobial therapy. Disease regression was achieved with a low frequency of AEs. These results provide preliminary data to inform a future randomized controlled trial (RCT).
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Antiinfecciosos Urinarios/uso terapéutico , Cistitis/tratamiento farmacológico , Síntomas del Sistema Urinario Inferior/tratamiento farmacológico , Piuria/fisiopatología , Infecciones Urinarias/tratamiento farmacológico , Cistitis/orina , Femenino , Humanos , Síntomas del Sistema Urinario Inferior/microbiología , Persona de Mediana Edad , New York , Dolor , Piuria/orina , Urinálisis , Infecciones Urinarias/orinaRESUMEN
INTRODUCTION AND HYPOTHESIS: This study sought to characterise the microbial ecology of the lower urinary tract in patients with symptoms of overactive bladder (OAB) using culture of the urinary urothelial cell sediment. The pathological significance of the microbiome was assessed through its relationship with known urothelial inflammatory markers and patient reported symptoms. METHODS: Adult female patients with OAB symptoms and asymptomatic controls were assessed at 12 study visits scheduled every 4 weeks. At each visit, all participants provided a clean-catch midstream urine (MSU) that was analysed to count white and uroepithelial cells, submitted to standard culture and spun urothelial-cell-sediment culture. Symptoms were assessed using validated questionnaires. RESULTS: This analysis shows that OAB patients differ consistently from controls, demonstrating differences in bacterial ecology (t -4.57, p 0.0001), in the microscopic pyuria count (t -6.37, p 0.0001) and presence of infected urothelial cells (t -4.21, p 0.0001). The primary outcome measure of bacterial growth [colony-forming units (CFU) ml-1] was higher in OAB patients than in controls throughout the 12 months. Data showed a correlation between symptoms and pyuria, with notable urgency correlating with pyuria and epithelial cell shedding. The routine urine cultures (with a threshold of reporting a positive result as 105 CFU/ml) were unable to distinguish OAB patients from controls. However, sediment cultures differed significantly, and there was a correlated increased immune response amongst OAB patients. CONCLUSIONS: This study supports the need to re-examine the OAB phenotype given this association with microbial colonisation.
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Piuria/microbiología , Vejiga Urinaria Hiperactiva/microbiología , Urotelio/microbiología , Anciano , Biomarcadores/orina , Estudios de Cohortes , Recuento de Colonia Microbiana/métodos , Femenino , Humanos , Microbiota , Persona de Mediana Edad , Método Simple Ciego , Urinálisis/métodosRESUMEN
We assessed the attitudes of UK Obstetrics and Gynaecology (O&G) trainees towards a caesarean delivery for maternal request (CDMR); and identified differences in attitude towards patients requesting CDMR and preferences for their own mode of delivery. An internet survey was constructed with questions covering trainees' personal preferences towards and experience of CDMR; attitudes to CDMR; and how they might treat patients making this request. From 02/2013 to 06/2013, the survey was sent electronically via email to all UK Deaneries to be forwarded to O&G trainees. Two hundred and forty O&G trainees participated; 78% female. 6/101 (6%) respondents had opted for CDMR in their first pregnancy. 28/131 (21%) would choose CDMR in their first pregnancy. Reasons for CDMR included concerns about pelvic floor/perineum, safety of the baby and convenience. 105/226 (46.4%) disagreed or strongly disagreed, and 67 (29.6%) agreed or strongly agreed with CDMR. 75/128 (58.6%) of respondents would grant CDMR to a patient; reasons included maternal choice, psychological concerns of the mother, perineal injury, pelvic floor. Our results are encouraging: positive attitudes of trainees towards vaginal delivery may help to reduce the rising caesarean rate. Impact Statement What is already known on this subject: Over the last 30 years, the rate of caesarean section in the UK has trebled and currently accounts for 25% of all deliveries. The rate of caesarean section in the UK has risen to 25% of all deliveries, incurring a financial burden and an excess clinical risk. With pressure to keep the caesarean rates low, understanding the attitudes and experience of obstetricians in training is important. What the results of this study add: Six percent of obstetric trainees, or their partners who had children had chosen a caesarean delivery for maternal request (CDMR), consistent with the population average. Twenty one percent of those who had not had children would choose CDMR. Both groups cited concerns over the pelvic floor as the predominant reason. Fifty nine percent of respondents would grant patients' request for CDMR. 29.6% of respondents agreed, and 46.4% disagreed with CDMR. Trainees' attitude to CDMR does not appear to be associated with whether or not they have had children, but does appear to be associated with whether they had experienced, or were planning to choose CDMR themselves in the future. What the implications are of these findings for clinical practice and/or further research: Training for obstetric trainees regarding the optimum way to manage patients' requests for, and clearer guidance on CDMR may be of benefit. It is important that obstetricians discuss the reasons behind such requests in order to individualise management.
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Actitud del Personal de Salud , Cesárea/estadística & datos numéricos , Procedimientos Quirúrgicos Electivos/psicología , Personal de Salud/psicología , Obstetricia/educación , Prioridad del Paciente/psicología , Adulto , Cesárea/efectos adversos , Parto Obstétrico/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Embarazo , Estudiantes de Medicina/psicología , Encuestas y CuestionariosRESUMEN
INTRODUCTION AND HYPOTHESIS: Urinary dipsticks and culture analyses of a mid-stream urine specimen (MSU) at 105 cfu ml-1 of a known urinary pathogen are considered the gold standard investigations for diagnosing urinary tract infection (UTI). However, the reliability of these tests has been much criticised and they may mislead. It is now widely accepted that pyuria (≥1 WBC µl-1) detected by microscopy of a fresh unspun, unstained specimen of urine is the best biological indicator of UTI available. We aimed to scrutinise the greater potential of symptoms analysis in detecting pyuria and UTI. METHODS: Lower urinary tract symptom (LUTS) descriptions were collected from patients with chronic lower urinary tract symptoms referred to a tertiary referral unit. The symptoms informed a 39-question inventory, grouped into storage, voiding, stress incontinence and pain symptoms. All questions sought a binary yes or no response. A bespoke software package was developed to collect the data. The study was powered to a sample of at least 1,990 patients, with sufficient power to analyse 39 symptoms in a linear model with an effect size of Cohen's f2 = 0.02, type 1 error probability = 0.05; and power (1-ß); 95% where ß is the probability of type 2 error). The inventory was administered to 2,050 female patients between August 2004 and November 2011. The data were collated and the following properties assessed: internal consistency, test-retest reliability, inter-observer reliability, internal responsiveness, external responsiveness, construct validity analysis and a comparison with the International Consultation on Incontinence Modular Questionnaire for female lower urinary tract symptoms (ICIQ-FLUTS). The dependent variable used as a surrogate marker of UTI was microscopic pyuria. An MSU sample was sent for routine culture. RESULTS: The symptoms proved reliable predictors of microscopic pyuria. In particular, voiding symptoms correlated well with microscopic pyuria (χ2 = 88, df = 1, p < 0.001). The symptom inventory has significant psychometric characteristics as below: test-retest reliability: Cronbach's alpha was 0.981; inter-observer reliability, Cronbach's alpha was 0.995, internal responsiveness F = 221, p < 0.001, external responsiveness F = 359, df = 5, p < 0.001. The correlation coefficients for the domains of the ICIQ-FLUTS were around R = 0.5, p < 0.001. CONCLUSION: This symptoms score performed well on the standard, psychometric validation. The score changed in response to treatment and in a direction appropriate to the changes in microscopic pyuria. It correlated with measures of quality of life. It would seem to make a good candidate for monitoring treatment progress in ordinary clinical practice.
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Síntomas del Sistema Urinario Inferior/orina , Piuria/orina , Encuestas y Cuestionarios , Infecciones Bacterianas , Femenino , Humanos , Londres , Síntomas del Sistema Urinario Inferior/microbiología , Masculino , Valor Predictivo de las Pruebas , Psicometría , Piuria/microbiología , Calidad de Vida , Reproducibilidad de los ResultadosRESUMEN
Overactive Bladder (OAB) is an idiopathic condition, characterized by urgency, urinary frequency, and urgency incontinence, in the absence of routinely traceable urinary infection. We have described microscopic pyuria (≥10 wbc/µl) in patients suffering from the worst symptoms. It is established that inflammation is associated with increased ATP release from epithelial cells, and extracellular ATP originating from the urothelium following increased hydrostatic pressure is a mediator of bladder sensation. Here, using bladder biopsy samples, we have investigated urothelial ATP signaling in OAB patients with microscopic pyuria. Basal, but not stretch-evoked, release of ATP was significantly greater from the urothelium of OAB patients with pyuria than from non-OAB patients or OAB patients without pyuria (<10 wbc/µl). Basal ATP release from the urothelium of OAB patients with pyuria was inhibited by the P2 receptor antagonist suramin and abolished by the hemichannel blocker carbenoxolone, which differed from stretch-activated ATP release. Altered P2 receptor expression was evident in the urothelium from pyuric OAB patients. Furthermore, intracellular bacteria were visualized in shed urothelial cells from â¼80% of OAB patients with pyuria. These data suggest that increased ATP release from the urothelium, involving bacterial colonization, may play a role in the heightened symptoms associated with pyuric OAB patients.
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Adenosina Trifosfato/metabolismo , Piuria/metabolismo , Transducción de Señal/fisiología , Vejiga Urinaria Hiperactiva/metabolismo , Urotelio/metabolismo , Carbenoxolona/farmacología , Femenino , Humanos , Masculino , Antagonistas del Receptor Purinérgico P2/farmacología , Piuria/complicaciones , Transducción de Señal/efectos de los fármacos , Suramina/farmacología , Uridina Trifosfato/farmacología , Vejiga Urinaria/efectos de los fármacos , Vejiga Urinaria/metabolismo , Vejiga Urinaria Hiperactiva/complicaciones , Urotelio/efectos de los fármacosRESUMEN
BACKGROUND: Adenosine-5'-triphosphate (ATP) is a neurotransmitter and inflammatory cytokine implicated in the pathophysiology of lower urinary tract disease. ATP additionally reflects microbial biomass thus has potential as a surrogate marker of urinary tract infection (UTI). The optimum clinical sampling method for ATP urinalysis has not been established. We tested the potential of urinary ATP in the assessment of lower urinary tract symptoms, infection and inflammation, and validated sampling methods for clinical practice. METHODS: A prospective, blinded, cross-sectional observational study of adult patients presenting with lower urinary tract symptoms (LUTS) and asymptomatic controls, was conducted between October 2009 and October 2012. Urinary ATP was assayed by a luciferin-luciferase method, pyuria counted by microscopy of fresh unspun urine and symptoms assessed using validated questionnaires. The sample collection, storage and processing methods were also validated. RESULTS: 75 controls and 340 patients with LUTS were grouped as without pyuria (n = 100), pyuria 1-9 wbc µl(-1) (n = 120) and pyuria ≥10 wbc µl(-1) (n = 120). Urinary ATP was higher in association with female gender, voiding symptoms, pyuria greater than 10 wbc µl(-1) and negative MSU culture. ROC curve analysis showed no evidence of diagnostic test potential. The urinary ATP signal decayed with storage at 23°C but was prevented by immediate freezing at ≤ -20°C, without boric acid preservative and without the need to centrifuge urine prior to freezing. CONCLUSIONS: Urinary ATP may have a role as a research tool but is unconvincing as a surrogate, clinical diagnostic marker.
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Adenosina Trifosfato/orina , Síntomas del Sistema Urinario Inferior/orina , Infecciones Urinarias/orina , Adenosina Trifosfato/análisis , Adulto , Anciano , Biomarcadores/orina , Estudios Transversales , Femenino , Estudios de Seguimiento , Humanos , Modelos Lineales , Síntomas del Sistema Urinario Inferior/fisiopatología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Prospectivos , Piuria/fisiopatología , Piuria/orina , Curva ROC , Valores de Referencia , Factores de Riesgo , Índice de Severidad de la Enfermedad , Método Simple Ciego , Urinálisis , Infecciones Urinarias/fisiopatologíaRESUMEN
Chronic lower urinary tract symptoms (LUTS), such as urgency and incontinence, are common, especially among the elderly, but their etiology is often obscure. Recent studies of acute urinary tract infections implicated invasion by Escherichia coli into the cytoplasm of urothelial cells, with persistence of long-term bacterial reservoirs, but the role of infection in chronic LUTS is unknown. We conducted a large prospective study with eligible patients with LUTS and controls over a 3-year period, comparing routine urine cultures of planktonic bacteria with cultures of shed urothelial cells concentrated in centrifuged urinary sediments. This comparison revealed large numbers of bacteria undetected by routine cultures. Next, we typed the bacterial species cultured from patient and control sediments under both aerobic and anaerobic conditions, and we found that the two groups had complex but significantly distinct profiles of bacteria associated with their shed bladder epithelial cells. Strikingly, E. coli, the organism most responsible for acute urinary tract infections, was not the only or even the main offending pathogen in this more-chronic condition. Antibiotic protection assays with shed patient cells and in vitro infection studies using patient-derived strains in cell culture suggested that LUTS-associated bacteria are within or extremely closely associated with shed epithelial cells, which explains how routine cultures might fail to detect them. These data have strong implications for the need to rethink our common diagnoses and treatments of chronic urinary tract symptoms.
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Bacterias/clasificación , Bacterias/aislamiento & purificación , Infecciones Bacterianas/microbiología , Síntomas del Sistema Urinario Inferior/etiología , Infecciones Urinarias/microbiología , Urotelio/microbiología , Adulto , Anciano , Enfermedad Crónica , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Microscopic pyuria is widely used as a surrogate marker of infection, although there is little data supporting its use in patients who present with non-acute LUTS. The effects of urinary storage, preservation, and the use of laboratory methods to enhance leucocyte detection, are also unclear. This large, prospective study highlights the poor performance of dipstick urine analysis, and direct microscopy, as surrogate markers of UTI in patients with LUTS. A series of laboratory analyses also examine the effects of urine handling and processing on test integrity, which have important implications for clinical practice. OBJECTIVE: To evaluate the diagnostic performance of pyuria as a surrogate marker of urinary tract infection (UTI) in patients with chronic lower urinary tract symptoms (LUTS), and determine the impact of sample storage, cytocentrifugation, and staining techniques, on test performance. PATIENTS AND METHODS: Between 2008 and 2011, we recruited 1223 patients (120 men; 1103 women; mean age 54 years) with one or more LUTS from a specialist urological outpatient service. We conducted a prospective observational study to determine the performance of microscopic pyuria ≥10 wbc/µL as a surrogate marker of UTI in patients with LUTS. All patients provided clean-catch midstream urine (MSU) samples for analysis, and routine microbiological cultures were used as our reference standard. We also scrutinised the performance of dipstick leucocyte esterase ≥ 'trace' in the detection of microscopic pyuria. The influence of sample handling and processing on test performance was examined in a series of laboratory studies. The effects of storage on leucocyte decay were determined using repeated microscopic assessments of individual urine samples, to plot temporal changes in leucocyte numbers. This study used varied storage conditions (≈20 °C and 4 °C), and boric acid preservation. Paired microscopic assessments were used to determine the effects of centrifugation on leucocyte salvage in spun/unspun samples (relative centrifugal force range 39-157 g). Similar methods were used to assess microscopic leucocyte quantification in stained/unstained urine (Sternheimer-Malbin protocol). RESULTS: The positive predictive value (PPV) and negative predictive value (NPV) of pyuria as a surrogate marker of UTI were 0.40 (95% confidence interval [CI] 0.37-0.43) and 0.75 (95% CI 0.73-0.76), respectively. The dipstick was unable to identify significant microscopic pyuria (≥10 wbc/µL) in 60% of the samples: PPV 0.51 (95% CI 0.48-0.55); NPV 0.75 (95% CI 0.73-0.76). Microscopic pyuria performed poorly as a surrogate of UTI defined by bacterial culture. Whilst refrigeration and preservation did retard leucocyte loss (F = 11; DF = 2; P < 0.001), 40% of cells were still lost by 4 h. Centrifugation had an unpredictable influence on cell salvage (coefficient of variation 5750%) and the use of staining to improve leucocyte detection proved ineffective (Z = -0.356; P = 0.72). CONCLUSIONS: Pyuria performs badly as a surrogate of UTI in patients with LUTS. This is exacerbated by cell loss during storage, and neither centrifugation, nor staining, appears to confer any diagnostic advantage. Clinicians should be alerted to the significant limitations of these tests.
Asunto(s)
Síntomas del Sistema Urinario Inferior/diagnóstico , Síntomas del Sistema Urinario Inferior/microbiología , Infecciones Urinarias/diagnóstico , Adulto , Biomarcadores , Hidrolasas de Éster Carboxílico/orina , Técnicas de Laboratorio Clínico , Femenino , Humanos , Síntomas del Sistema Urinario Inferior/complicaciones , Síntomas del Sistema Urinario Inferior/orina , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Piuria/etiología , Infecciones Urinarias/complicaciones , Infecciones Urinarias/orinaRESUMEN
PURPOSE: Diagnosing urinary infection in patients with chronic lower urinary tract symptoms without dysuria is a critical step. In this study we scrutinize the sensitivity and specificity of dipstick urinalysis and microscopic pyuria (10 or more white blood cells per microl) to identify infection in such patients. MATERIALS AND METHODS: This was a prospective, blinded, observational cohort study of urological outpatients with painless lower urinary tract symptoms. Midstream and catheter urine samples were analyzed. A total of 508 midstream urine samples were used to compare leukocyte esterase, nitrite dipstick and urine microscopy with cultures seeking 10(5) cfu/ml. Similarly 470 catheter urine samples were used to compare the same surrogates with 10(5) cfu/ml and with an enhanced culture method seeking 10(2) cfu/ml. A comparison of leukocyte esterase against microscopic pyuria was made using the 508 midstream and 470 catheter specimens of urine. Midstream urine specimens were provided by 42 normal volunteers for comparison. RESULTS: For a midstream urine culture at 10(5) cfu/ml leukocyte esterase was 56% sensitive, nitrite was 10% sensitive and microscopic pyuria was 56% sensitive. Specificities were 66%, 99% and 72%, respectively. For a catheter specimen of urine culture at 10(5) cfu/ml leukocyte esterase was 59% sensitive, nitrite was 20% sensitive and microscopic pyuria was 66% sensitive. Specificities were 84%, 97% and 73%, respectively. The enhanced culture of catheter specimen of urine at 10(2) cfu/ml was positive in 29% of patients vs 15% at 10(5) cfu/ml. CONCLUSIONS: Despite official guidelines and widespread use these tests cannot be considered appropriate for diagnosing urinary tract infection in patients with lower urinary tract symptoms, and should be abandoned in this context.
Asunto(s)
Biomarcadores/orina , Pacientes Ambulatorios , Urinálisis/métodos , Infecciones Urinarias/orina , Adulto , Hidrolasas de Éster Carboxílico/orina , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Disuria , Femenino , Humanos , Masculino , Microscopía , Persona de Mediana Edad , Estudios Prospectivos , Piuria/microbiología , Piuria/orina , Tiras Reactivas , Sensibilidad y Especificidad , Programas Informáticos , Encuestas y Cuestionarios , Infecciones Urinarias/microbiologíaRESUMEN
PURPOSE: We validated a simple scale to measure urinary urgency. MATERIALS AND METHODS: The new 10-item scale was validated using data from experiments using a single group repeated measure design. A total of 475 patients, including 411 females and 64 males, with a mean age of 57.3 years who had been diagnosed with overactive bladder were treated with a bladder retraining regimen and antimuscarinic agent (10 mg oxybutynin controlled release per night or 4 mg tolterodine slow release per night). At each visit patient urge symptoms were recorded by the scale. Reported average daily frequency and incontinence episodes were also recorded. Of patients who were not satisfied with the symptoms 130 had 25 mg imipramine per night added to their prescription and in 130 treatment was changed to 10 mg solifenacin per night. RESULTS: Construct validity was tested by comparing the urgency scale to frequency and to incontinence (Spearman's rank correlation coefficient r = 0.38, p <0.001 and r = 0.15, p <0.001, respectively). Internal consistency showed Cronbach's alpha = 0.83. Test-retest reliability was determined in 30 patients and interobserver reliability was determined in 58 (Pearson's r = 0.99, p <0.001 and r = 0.99, p <0.001, respectively). Internal responsiveness in the imipramine add-on study in 130 patients showed a standardized response mean of 0.6 (p <0.001) and in the solifenacin swap study in 130 it showed a standardized response mean of 0.69, while external responsiveness showed a standardized response mean of 0.69 (each p <0.001). CONCLUSIONS: This scale succeeded in all validation studies. This new scale may prove useful for measuring between-drug differences in efficacy and for monitoring treatment responses in patients with overactive bladder. It now must be tested in a proper double-blind, randomized, controlled trial.