The epidemiology of sepsis in paediatric intensive care units in Brazil (the Sepsis PREvalence Assessment Database in Pediatric population, SPREAD PED): an observational study.

BACKGROUND: Data on the prevalence and mortality of paediatric sepsis in resource-poor settings are scarce. We aimed to assess the prevalence and in-hospital mortality of severe sepsis and septic shock treated in paediatric intensive care units (PICUs) in Brazil, and risk factors for mortality. METHODS: We performed a nationwide, 1-day, prospective point prevalence study with follow-up of patients with severe sepsis and septic shock, using a stratified random sample of all PICUs in Brazil. Patients were enrolled at each participating PICU on a single day between March 25 and 29, 2019. All patients occupying a bed at the PICU on the study day (either admitted previously or on that day) were included if they were aged 28 days to 18 years and met the criteria for severe sepsis or septic shock at any time during hospitalisation. Patients were followed up until hospital discharge or death, censored at 60 days. Risk factors for mortality were assessed using a Poisson regression model. We used prevalence to generate national estimates. FINDINGS: Of 241 PICUs invited to participate, 144 PICUs (capacity of 1242 beds) included patients in the study. On the day of the study, 1122 children were admitted to the participating PICUs, of whom 280 met the criteria for severe sepsis or septic shock during hospitalisation, resulting in a prevalence of 25·0% (95% CI 21·6-28·8), with a mortality rate of 19·8% (15·4-25·2; 50 of 252 patients with complete clinical data). Increased risk of mortality was associated with higher Pediatric Sequential Organ Failure Assessment score (relative risk per point increase 1·21, 95% CI 1·14-1·29, p<0·0001), unknown vaccination status (2·57, 1·26-5·24; p=0·011), incomplete vaccination status (2·16, 1·19-3·92; p=0·012), health care-associated infection (2·12, 1·23-3·64, p=0·0073), and compliance with antibiotics (2·38, 1·46-3·86, p=0·0007). The estimated incidence of PICU-treated sepsis was 74·6 cases per 100 000 paediatric population (95% CI 61·5-90·5), which translates to 42 374 cases per year (34 940-51 443) in Brazil, with an estimated mortality of 8305 (6848-10 083). INTERPRETATION: In this representative sample of PICUs in a middle-income country, the prevalences of severe sepsis or septic shock and in-hospital mortality were high. Modifiable factors, such as incomplete vaccination and health care-associated infections, were associated with greater risk of in-hospital mortality. FUNDING: Fundação de Amparo à Pesquisa do Estado de São Paulo and Conselho Nacional de Desenvolvimento Científico e Tecnológico. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

Sensory evoked cortical potentials of the lower urinary tract in healthy men.

AIMS: To assess the afferent innervation of various locations in the male lower urinary tract (LUT) using sensory evoked cortical potentials (SEPs). METHODS: Twelve healthy men (mean age: 29.6 ± 7.2 years, mean height: 1.8 ± 0.1 m) underwent repetitive slow (0.5 Hz/1 ms) and fast (3 Hz/0.2 ms) electrical stimulations of bladder (dome/trigone) and urethral (proximal/membranous/distal) locations with simultaneous cortical SEP recording (Cz-Fz). Latencies (ms) and peak-to-peak amplitudes (µV) for SEP components P1, N1, and P2 were analyzed. Tibial SEPs were assessed as methodological control. The reproducibility was investigated from between visits and inter-rater assessments using Bland-Altman plots. Statistical tests comprised analysis of variance (ANOVA), linear regressions, and paired t-tests. Values are given as mean ± standard deviation. RESULTS: Typical LUTSEPs with P1, N1, and P2 components were successfully detected (100% responder rate) for slow but less successfully for fast stimulation. The slow stimulation provided reproducible LUTSEPs with position specific N1 latencies: dome 125.6 ± 21.3 ms, trigone 122.9 ± 20.5 ms, proximal- 116.1 ± 21.4 ms, membraneous- 118.8 ± 29.3 ms, and distal urethra 108.8 ± 17.8 ms. Despite good inter-rater agreement, latency variability between and within subjects was higher for LUTSEPs than for tibial SEPs. N1 latencies became shorter (P < 0.01) with increasing subject age for bladder dome and distal urethra stimulation. CONCLUSIONS: LUTSEPs can be successfully obtained for different LUT locations in men using slow electrical stimulation. Location specific differences in N1 latencies may indicate different local afferent innervation. Larger variability of LUTSEPs versus tibial SEPs may be related to the more challenging approach and afferent fibre access within the LUT. Further studies optimizing measurement and analysis approach are required.

Sensory function assessment of the human male lower urinary tract using current perception thresholds.

AIMS: To evaluate the feasibility and reliability of current perception threshold (CPT) measurement for sensory assessment of distinct locations in the male lower urinary tract (LUT). METHODS: Twelve male subjects (>18 years) without LUT symptoms or medical comorbidities were eligible. CPTs were determined twice (interval: 7-20 days) at the bladder dome, trigone and the proximal, membranous, and distal urethra. Square wave electrical stimulation of 3 Hz/0.2 ms and 0.5 Hz/1 ms was applied using a transurethral 8F catheter placed under fluoroscopic control. Bladder volume was kept constant (60 mL) using a second 10F catheter. Repetitive measurements and reliability were assessed by analysis of variance (ANOVA) and intraclass correlation coefficient (ICC). RESULTS: The ANOVA revealed significant main effects for stimulation site (P = 0.008) and type of stimulation (P < 0.001) with lower CPTs for 0.5 Hz/1 ms compared to 3 Hz/0.2 ms. There was no significant effect for visit number (P = 0.061). CPTs were higher for bladder dome than for proximal (0.5 Hz/1 ms: P = 0.022; 3 Hz/0.2 ms: P = 0.022) and distal urethra (0.5 Hz/1 ms: P = 0.026; 3 Hz/0.2 ms: P = 0.030). Reliability of CPT measurements was excellent to good (ICC = 0.67-0.96) except for the bladder dome (5 Hz/1 ms: ICC = 0.45; 3 Hz/0.2 ms: ICC = 0.20) and distal urethra (3 Hz/0.2 ms: ICC = 0.57). CONCLUSIONS: CPTs can be reliably detected at different LUT locations. However, alert and compliant subjects are essential. CPTs of LUT may become a complementary assessment method providing information on responsiveness and sensitivity of afferent LUT nerves. This is especially relevant for urethral afferents, which are not covered by standard urodynamic investigations. Neurourol. Urodynam. 36:469-473, 2017. © 2016 Wiley Periodicals, Inc.

Avaliação do estado nutricional em pacientes hospitalizados com cirrose hepática / Nutritional assessment in hospitalized patients with liver cirrhosis

Introdução: A cirrose surge devido a um processo crônico e progressivo de inflamações. O tipo mais comum é a cirrose hepática (CH). Pacientes com CH apresentam baixa ingestão alimentar, alterações bioquímicas e grande depleção de massa muscular. A avaliação do estado nutricional pode detectar as alterações do estado nutricional e fornecer informação prognóstica. O diagnóstico nutricional dos pacientes com CH representa grande desafio devido à retenção hídrica frequentemente encontrada. Objetivo: Caracterizar o estado nutricional dos pacientes com CH hospitalizados. Método: O método de avaliação utilizado no estudo foi a Avaliação Global do Royal Free Hospital (RFH-GA), um instrumento validado em 2006 no Royal Free Hospital de Londres, que consiste em uma avaliação nutricional específica para pacientes cirróticos. Resultados: Foram avaliados 26 pacientes, predominantemente do sexo masculino, com média de idade de 54,2 anos, sendo a principal etiologia a cirrose hepática alcóolica. As seguintes variáveis foram consideradas: sintomas gastrointestinais, disfunções clínicas, consumo alimentar, avaliação da composição corporal subjetiva e antropometria objetiva. Conclusão: O presente trabalho verificou alta taxa de desnutrição e o instrumento de avaliação do RFH-GA foi adequado para classificação do estado nutricional.(AU)

Introduction: Cirrhosis arises due to a chronic and progressive process of inflammation, the most common type is liver cirrhosis (LC). LC patients have low food intake, biochemical and great loss of muscle mass. The nutritional assessment can detect changes in the nutritional status and provide prognostic information. Nutritional diagnosis of patients with LC is a challenge due to water retention often found. Objective: To characterize the nutritional status of hospitalized patients with LC. Methods: The evaluation method used in the study was the Global Assessment of the Royal Free Hospital (RFH-GA), a nutritional assessment tool validated in 2006 at the Royal Free Hospital in London, that consists of a specific nutritional assessment for cirrhotic patients. Results: We evaluated 26 patients, predominantly male, with an average age of 54.2 years, the main cause being the alcoholic liver cirrhosis. The following variables were considered: gastrointestinal symptoms, clinical disorders, food intake, body composition assessment of subjective and objective anthropometry. Conclusion: The present work verified a high rate of malnutrition and the evaluation tool for the RFH-GA was adequate to assess the nutritional status.(AU)

Sensory evoked potentials of the bladder and urethra in middle-aged women: the effect of age.

OBJECTIVES: To investigate feasibility, reproducibility and age dependency of sensory evoked cortical potentials (SEPs) after electrical stimulation of different locations in the lower urinary tract (LUT) in a cohort of middle-aged healthy women. SUBJECTS AND METHODS: In a group of 10 healthy middle-aged women [mean (sd) height 165 (5) cm and age 43 (6) years), electrical stimulation (0.5 and 3 Hz) was applied to the bladder dome, trigone, and proximal and distal urethra. SEPs were recorded at the Cz electrode with reference to Fz. All measurements were repeated three times with an interval of 3-5 weeks. Current perception thresholds (CPT), SEP latencies and amplitudes were analysed. Results were compared with a group of younger women published previously. RESULTS: LUT SEPs demonstrated two positive (P1, P2) and one negative peak (N1). The mean (sd) N1 latency was 108.9 (7.8), 116.2 (10.7), 113.2 (13.4) and 131.3 (35.6) ms for the bladder dome, trigone, proximal and distal urethra, respectively. N1 latencies, except for the distal urethra, were significantly shorter than those in younger women. Taking all data, i.e. young and middle-aged women, into account, there was a significant negative correlation between the variable age and CPT/dome (r = -0.462, P = 0.04) and N1 latency/dome (r = -0.605, P = 0.005) and a significant positive correlation between the variable age and N1P2 amplitude/dome (r = 0.542, P = 0.014). CONCLUSION: LUT SEPs can be induced in middle-aged women with reliable N1 responses. Unexpectedly, N1 responses reveal a shortening with increasing age particularly when compared with younger women. Changes in sensory afferents may be explained by age-related qualitative reorganisations within the urothelium and suburothelium potentially altering afferent nerve excitability, which may have an impact on the development of non-neurological LUT symptoms (LUTS, e.g. overactive bladder) in women.

Supraspinal Control of Urine Storage and Micturition in Men--An fMRI Study.

Despite the crucial role of the brain in the control of the human lower urinary tract, little is known about the supraspinal mechanisms regulating micturition. To investigate the central regulatory mechanisms activated during micturition initiation and actual micturition, we used an alternating sequence of micturition imitation/imagination, micturition initiation, and actual micturition in 22 healthy males undergoing functional magnetic resonance imaging. Subjects able to micturate (voiders) showed the most prominent supraspinal activity during the final phase of micturition initiation whereas actual micturition was associated with significantly less such activity. Initiation of micturition in voiders induced significant activity in the brainstem (periaqueductal gray, pons), insula, thalamus, prefrontal cortex, parietal operculum and cingulate cortex with significant functional connectivity between the forebrain and parietal operculum. Subjects unable to micturate (nonvoiders) showed less robust activation during initiation of micturition, with activity in the forebrain and brainstem particularly lacking. Our findings suggest that micturition is controlled by a specific supraspinal network which is essential for the voluntary initiation of micturition. Once this network triggers the bulbospinal micturition reflex via brainstem centers, micturition continues automatically without further supraspinal input. Unsuccessful micturition is characterized by a failure to activate the periaqueductal gray and pons during initiation.

Acute spinal cord injury--do ambulatory patients need urodynamic investigations?

PURPOSE: We compared the urodynamic parameters of ambulatory vs nonambulatory acute spinal cord injured patients. MATERIALS AND METHODS: A total of 27 women and 33 men (mean age 58 years) with neurogenic lower urinary tract dysfunction due to acute spinal cord injury (duration of injury less than 40 days) were prospectively evaluated. The patients were dichotomized according to the mobility for moderate distances subscale of the SCIM (Spinal Cord Independence Measure) version III into ambulatory (score of 3 or greater) and nonambulatory (score less than 3). Videourodynamic parameters including maximum detrusor pressure during the storage phase, bladder compliance, detrusor overactivity, detrusor external sphincter dyssynergia and vesicoureterorenal reflux were compared between the groups. RESULTS: Of the 60 patients with acute spinal cord injury 17 were ambulatory and 43 were nonambulatory. Mean ± SD duration of injury at urodynamic investigation was 30 ± 8 days. The lesion level was cervical in 14 patients, thoracic in 28 and lumbar/sacral in 18. Comparing unfavorable urodynamic parameters, no significant differences were found between ambulatory vs nonambulatory patients in terms of a high pressure system during the storage phase (29% vs 33%, p = 0.81), a low compliance bladder (12% vs 7%, p = 0.54), detrusor overactivity (24% vs 47%, p = 0.1), detrusor external sphincter dyssynergia (18% vs 21%, p = 0.77) and vesicoureterorenal reflux (0% vs 5%, p = 0.36). CONCLUSIONS: Ambulatory and nonambulatory patients with acute spinal cord injury have a similar risk of unfavorable urodynamic measures. Thus, we strongly recommend the same neurourological assessment including urodynamic investigations in all acute spinal cord injury patients independent of the ability to walk.

Sensory evoked potentials of the human lower urinary tract.

PURPOSE: We investigated the feasibility and reliability of recording sensory evoked potentials after lower urinary tract electrical stimulation. Sensory evoked potentials might reveal improved insights into afferent processing in specific locations of the human lower urinary tract. MATERIALS AND METHODS: Electrical stimulation (0.5 and 3 Hz) was applied to the bladder dome and trigone, and the proximal and distal urethra using a transurethral catheter. Cortical sensory evoked potentials were recorded at the Cz electrode with reference to the Fz electrode. All measurements were repeated 3 times for reliability assessment using the ICC. RESULTS: Ten healthy female subjects with a mean ± SD age of 23 ± 4 years and a mean height of 168 ± 6 cm were included in the study. The most prominent, consistent sensory evoked potential landmark across different locations was the first negative peak. In all subjects after 0.5 Hz stimulation, the first negative peak was reliably recorded at a mean of 128.8 ± 23.8, 141.9 ± 51.5, 133.1 ± 32.1 and 132.5 ± 33.6 milliseconds (ICC 0.88, 0.83, 0.90 and 0.81) at the bladder dome, trigone, proximal and distal urethra, respectively. After 3 Hz stimulation, no reliable sensory evoked potentials could be recorded. CONCLUSIONS: Sensory evoked potentials can be reliably recorded from different lower urinary tract locations after 0.5 Hz stimulation with a characteristic negativity at about 130 milliseconds. These latencies are compatible with a conduction velocity in the range of 3 to 10 m per second, corresponding to transmission by A-δ fibers. The inability to retrieve reliable responses at 3 Hz stimulation might potentially be related to less involvement of fast conduction fibers, ie A-ß, in afferent sensation along the human lower urinary tract. The value of a more distinct diagnosis of sensory sensation in lower urinary tract disorders must be evaluated in further studies.

Is there a direct antimicrobial effect of botulinum neurotoxin type A?

UNLABELLED: Study Type--Therapy (case series) Level of Evidence 4. What's known on the subject? and What does the study add? Several studies describe a reduction of symptomatic urinary tract infections in patients with neurogenic detrusor overactivity after intradetrusor injections of botulinum neurotoxin A (BoNT/A). It was, however, unclear if a direct antibacterial effect of BoNT/A plays a role in this clinical observation. This is the first study to investigate a potential antibacterial effect of two frequently used BoNT/A formulations (i.e. Botox® and Dysport®), providing evidence that BoNT/A does not exert an antibacterial effect on lower urinary tract pathogens. OBJECTIVE: • To determine a potential direct antimicrobial effect of botulinum neurotoxin type A (BoNT/A). MATERIALS AND METHODS: • A prospective study was carried out using onabotulinumtoxin A (Botox®) and abobotulinumtoxin A (Dypsort®) in agar diffusion and broth microdilution assays with various clinical urinary tract isolates (Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Pseudomonas aeruginosa, Acinetobacter baumannii, Citrobacter freundii, Klebsiella oxytoca and Bacillus subtilis). • Inhibition zones (mm) of bacteria around a disc containing 20 µL saline with 4 IU of Botox® were measured in the agar diffusion assay. • Minimal inhibitory concentrations (MICs, IU/mL) of both toxins for all bacteria were determined in the broth microdilution assay after overnight incubation at 35 °C. RESULTS: • There was no inhibition zone in the agar diffusion assays with any bacterial strain. • The microdilution test using Botox® and Dysport® showed bacterial growth in all dilutions, i.e. MICs > 20 and >100 IU/mL for Botox® and Dysport®, respectively. CONCLUSIONS: • BoNT/A has no direct antimicrobial effect. • The reduced frequency of symptomatic urinary tract infections (sUTIs) in patients with neurogenic detrusor overactivity (NDO) after BoNT/A intradetrusor injections seems to be caused by different indirect mechanisms, which are still not completely understood.

External urethral sphincter pressure measurement: an accurate method for the diagnosis of detrusor external sphincter dyssynergia?

BACKGROUND: Combined pelvic floor electromyography (EMG) and videocystourethrography (VCUG) during urodynamic investigation are the most acceptable and widely agreed methods for diagnosing detrusor external sphincter dyssynergia (DESD). Theoretically, external urethral sphincter pressure (EUSP) measurement would provide enough information for the diagnosis of DESD and could simplify the urodynamic investigation replacing combined pelvic floor EMG and VCUG. Thus, we evaluated the diagnostic accuracy of EUSP measurement for DESD. PATIENTS #ENTITYSTARTX00026; METHODS: A consecutive series of 72 patients (36 women, 36 men) with neurogenic lower urinary tract dysfunction able to void spontaneously was prospectively evaluated at a single university spinal cord injury center. Diagnosis of DESD using EUSP measurement (index test) versus combined pelvic floor EMG and VCUG (reference standard) was assessed according to the recommendations of the Standards for Reporting of Diagnostic Accuracy Initiative. RESULTS: Using EUSP measurement (index test) and combined pelvic floor EMG and VCUR (reference standard), DESD was diagnosed in 10 (14%) and in 41 (57%) patients, respectively. More than half of the patients presented discordant diagnosis between the index test and the reference standard. Among 41 patients with DESD diagnosed by combined pelvic floor EMG and VCUR, EUSP measurement identified only 6 patients. EUSP measurement had a sensitivity of 15% (95% CI 5%-25%), specificity of 87% (95% CI 76%-98%), positive predictive value of 60% (95% CI 30%-90%), and negative predictive value of 56% (95% CI 44%-68%) for the diagnosis of DESD. CONCLUSIONS: For diagnosis of DESD, EUSP measurement is inaccurate and cannot replace combined pelvic floor EMG and VCUR.

Neurogenic lower urinary tract dysfunction--do we need same session repeat urodynamic investigations?

PURPOSE: We investigated whether same session repeat urodynamic investigations are needed in patients with neurogenic lower urinary tract dysfunction. MATERIALS AND METHODS: A consecutive series of 226 patients with neurogenic lower urinary tract dysfunction who underwent same session repeat urodynamic investigation was prospectively investigated at a single university spinal cord injury center. Urodynamics were done according to the good urodynamic practices recommended by the International Continence Society. All 226 patients underwent same session repeat consecutive filling cystometry and 88 also underwent pressure flow studies if they could void spontaneously. Repeatability of the 2 measurements was assessed using the Bland and Altman 95% limits of agreement, and the κ statistic. RESULTS: Mean age of the 226 patients enrolled was 52 years (range 18 to 90). Of the patients 94 (42%) were women and 132 were (58%) men. Detrusor overactivity repeatability was excellent between the 2 urodynamic investigations (κ=0.87, 95% CI 0.80-0.94). For all other urodynamic parameters assessed there were wide 95% limits of agreement for differences in the parameters, indicating poor repeatability. CONCLUSIONS: In same session repeat urodynamic investigations of patients with neurogenic lower urinary tract dysfunction detrusor overactivity demonstrates excellent repeatability but all other urodynamic parameters show insufficient agreement. Thus, we strongly recommend that clinical decision making not be based on a single urodynamic investigation since repeat measurements may yield completely different results.