Validation of the Vancouver Symptom Score Questionnaire for bladder and bowel dysfunction for Brazilian children and adolescents.

OBJECTIVE: This study aimed to translate, and perform a cross-cultural adaptation, and validation of the Vancouver Symptom Score (VSS) for bladder and bowel dysfunction (BBD) for Brazilian children and adolescents Materials and Methods: Six steps were performed for the translation and cross-cultural adaptation: (1) translation, (2) synthesis of translations, (3) back-translation, (4) pre-final version of the translated instrument, (5) pilot test and degree of comprehensibility and (6) elaboration of the Brazilian version of the VSS. For validation, the Brazilian Dysfunctional Voiding Score (DVSS) questionnaire was used. RESULTS: Validation was performed on a sample of 107 children and adolescents with a mean age of 9.2 ± 2.84 years, presenting BBD and 107 without BBD (control group-CG). There was a positive correlation (r = 0.91, 95% CI 0.88 to 0.93, p < 0.0001) between total VSS score and total DVSS score. VSS was higher in patients with BBD (p < 0.0001). The internal consistency estimated by Cronbach's alpha was 0.87 for patients with BBD. The VSS showed excellent diagnostic accuracy in detecting cases, with an area under the ROC curve of 98% (95% CI 0.96 to 0.99, p < 0.001). A cut-off value of >11 points produced a sensitivity of 100% (95% CI 96.4% to 100%) and a specificity of 91.8% (95% CI 85.1% to 95.6%). CONCLUSION: The translated, cross-culturally adapted, and validated VSS for the Brazilian population is a reliable and valid tool to identify symptoms of BBD in children and adolescents aged five to 16 years, whose first language is Brazilian Portuguese.

Pharmacogenomic markers of glucocorticoid response in congenital adrenal hyperplasia.

Glucocorticoids (GC) replacement are the mainstay treatment for 21-hydroxylase deficiency (21-OHD), the most common cause of congenital adrenal hyperplasia (CAH), in its classical form. There are novel insights into the genetic basis of the GC action diversity that point to an important role for GC receptor (GR) gene polymorphisms, suggesting a possible modulation in occurrence of metabolic disorders, what may be relevant to clinical management of 21-OHD. The aim of this study was to investigate whether the five GR gene polymorphisms Tth111I, ER22, 23EK, BclI, 9ß (rs10052957, rs6189, rs6190, rs41423247, rs6198) and their combination into haplotypes are associated to different GC response in a cohort of classic 21-OHD subjects. GR genotype-phenotype associations were explored after a dexamethasone suppression test using very low-doses (VLD-DST), 20 and 40 µg/m². The final sample (n = 28) was selected based on the 102 individuals' previous genotypes classification, according to literature data of GC sensitivity or resistance. Thus, only patients with GC increased resistance (n = 18) or increased sensitivity (n = 10) profiles were selected. Out of 28 subjects aged 12 (2-34) years enrolled in this study, 75% were females, 75% presented the salt-wasting form (SW) and 25% the simple virilizing form (SV). Subjects who carried Tth111I and 9ß, associated or not to the ER22/23EK variants, showed an impaired DST response. Results did not differ significantly according to gender or body mass index. SV subjects with GC hypersensitivity-genotypes showed decreased average cortisol levels compared to those with GC resistance-genotypes (p = 0.0023). The Tth111I + 9ß/ Wild or Tth111I + ER22/23EK + 9ß/ Wild genotypes were associated to GC resistance in this population. This finding may be relevant given the challenges posed by therapeutic management with GC in CAH.

Relationship between primary monosymptomatic enuresis and process toilet training: a case-control.

OBJECTIVE: Primary monosymptomatic nocturnal enuresis (PMNE) is a prevalent condition in childhood, and the pathophysiology is multifactorial. This study investigated the relationship between the toilet training process (TT) and PMNE in children and adolescents. PATIENTS AND METHODS: A case-control study was carried out from 2015 to 2020. The presence of PMNE was identified according to International Children's Continence Society criteria. A semi-structured questionnaire was applied to assess TT. RESULTS: The study included 103 children and adolescents with PMNE and 269 participants with normal psychomotor development without PMNE (control group [CG]). Readiness signals were more remembered and less frequent in participants with PMNE (p=0.001) when compared to control group. No differences were found between the groups regarding the onset age of the daytime TT (p= 0.10), the nocturnal TT (p=0.08), the acquisition of daytime continence (p=0.06), and the type of equipment used for the TT (p=0.99). The use of Child-Oriented approach in group of children with enuresis was lower than in controls [87.4% (90/103) versus 94% (250/266)], respectively (OR= 0.44, 95% CI 0.21-0.94, p = 0.039). CONCLUSIONS: The age of onset of TT, acquisition of daytime continence, and the type of equipment were not associated with higher occurrence of PMNE. On the other hand, the Child-Oriented approach was a protective factor for the occurrence of PMNE.

Inflammatory biomarkers in children with cerebral palsy: A systematic review.

BACKGROUND: An exacerbated systemic inflammatory response has been associated with the occurrence of central nervous system injuries that may determine, in long term, motor, sensorial and cognitive disabilities. Persistence of this exacerbated inflammatory response seems to be involved in the pathophysiology of cerebral palsy (CP). METHODS: A systematic search was conducted in Bireme, Embase, PubMed and Scopus including studies that were published until August 2019. The key words used were "cerebral palsy", "brain injury", "inflammation", "oxidative stress", "cytokines", "chemokines", "neuropsychomotor development", "neurodevelopment outcomes" and "child". The quality of the eligible studies was determined according to the criteria suggested by the Newcastle-Ottawa Scale (NOS). RESULTS: Fourteen eligible studies aimed to investigate the association between peripheral inflammatory molecules and neurodevelopment in infants. The studies differed regarding CP-related risk factors and its classification. Inflammatory proteins were measured in blood, plasma, serum, cerebrospinal fluid or urine. In ten studies, higher circulating levels of cytokines, including IL-1ß, IL-6, TNF and CXCL8/IL-8, were associated with abnormal neurological findings. CONCLUSION: The investigation of the potential association between inflammatory molecules and neurological development in children with CP requires further original studies in order to clarify the influence of prenatal and perinatal inflammation on neurological outcomes.

A clinical predictive model of chronic kidney disease in children with posterior urethral valves.

BACKGROUND: Posterior urethral valves (PUVs) are associated with severe consequences to the urinary tract and are a common cause of chronic kidney disease (CKD). The aim of this study was to develop clinical predictive model of CKD in a cohort of patients with PUVs. METHODS: In this retrospective cohort study, 173 patients with PUVs were systematically followed up at a single tertiary unit. The primary endpoint was CKD ≥ stage 3. Survival analyses were performed by Cox regression proportional hazard models with time-fixed and time-dependent covariables. RESULTS: Mean follow-up time was 83 months (SD, 70 months). Sixty-five children (37.6%) developed CKD stage ≥ 3. After adjustment by the time-dependent Cox model, baseline creatinine, nadir creatinine, hypertension, and proteinuria remained as predictors of the endpoint. After adjustment by time-fixed model, three variables were predictors of CKD ≥ stage 3: baseline creatinine, nadir creatinine, and proteinuria. The prognostic risk score was divided into three categories: low-risk (69 children, 39.9%), medium-risk (45, 26%), and high-risk (59, 34.1%). The probability of CKD ≥ stage 3 at 10 years age was estimated as 6%, 40%, and 70% for patients assigned to the low-risk, medium-risk, and high-risk groups, respectively (P < 0.001). The main limitation was the preclusion of some relevant variables, especially bladder dysfunction, that might contribute to a more accurate prediction of renal outcome. CONCLUSION: The model accurately predicts the risk of CKD in PUVs patients. This model could be clinically useful in applying timely intervention and in preventing the impairment of renal function.

Urinary levels of TGF ß-1 and of cytokines in patients with prenatally detected nephrouropathies.

This study aimed to identify noninvasive biomarkers of clinically significant nephrouropathies in patients with antenatal renal and/or urinary tract alterations. Spot-urine levels of interleukin-6 (IL-6), transforming growth factor-ß1 (TGF-ß1) and tumor necrosis factor-α (TNF-α) were measured in 100 patients with antenatal detected nephrouropathies. Patients were divided in idiopathic hydronephrosis (n = 47), urinary tract malformations (n = 35), and dysplastic kidneys (n = 18). Urinary concentrations of TGF-ß1, IL-6, and TNF-α were compared between groups according to clinical and image findings. Receiver-operating characteristic (ROC) curves were analyzed for the overall diagnostic accuracy of TGF-ß1, IL-6, and TNF-α levels in discriminating infants with nephrouropathies. No significant differences in urinary TGF- ß1, IL-6, and TNF-α levels were found in the comparison between the groups. TGF-ß1 levels tended to be higher in patients with renal hypodysplasia compared to idiopathic hydronephrosis (p = 0.07). Twenty-nine patients had reduced DMSA uptake. In these cases, absolute urinary concentration of TGF-ß1 and levels standardized for creatinine were significantly higher than in patients with normal DMSA uptake, while IL6 and TNF-α did not differ between groups. Urinary cytokine measurements were not useful as a screening test for clinically significant nephrouropathies. Conversely, increased concentrations of TGF-ß1 pointed out to renal damage as indicated by reduced DMSA uptake.

Comparison between automated and manual measurements of carotid intima-media thickness in clinical practice.

BACKGROUND AND AIM: The measurement of carotid intima-media thickness (cIMT) has been used as a marker of arterial wall disease. Manual measurements have been performed in most epidemiological studies, but, due to the introduction of new technologies, automated software has been increasingly used. This study aimed to compare manual versus automated cIMT measurements in common carotid (CC), bifurcation (BIF), and internal carotid (IC). METHODS: Automated and manual cIMT measurements were performed online in 43 middle-aged females. Carotid segment measurements were compared by Bland-Altman plot and the variation and repeatability coefficients between observers were also determined for comparison. RESULTS: The average timespan for manual measurements (57.30 s) were significantly higher than for automated measurements (2.52 s). There were no systematic errors between methods in any carotid segments. The variation coefficient was 5.54% to 6.34% for CC and BIF, 9.76% for IC, and absolute differences were 85% below 0.1 mm and 70% below 0.05 mm. Interobserver agreement showed no systematic error. The variation and the repeatability coefficients were better for the automated than manual measures. CONCLUSION: Although both methods are reliable for cIMT measurements, the automated technique allows faster evaluation with lesser variability for all carotid segments currently used in atherosclerosis research.

Early awakening and extubation with remifentanil in ventilated premature neonates.

BACKGROUND: Morphine is one of the most commonly used drugs for sedation and analgesia during mechanical ventilation, but its pharmacological profile has limitations, such as prolonged duration of action, especially in premature neonates. Because of its very short context-sensitive half-time, remifentanil has rapid onset and quickly decreases in plasma concentration after interrupting administration. The aim of the present study was to compare a continuous infusion of remifentanil and morphine during mechanical ventilation of premature neonates with respiratory distress syndrome (RDS). METHODS: Twenty premature neonates (28-34 weeks) with RDS were randomized in a prospective double-blinded study to receive either a continuous infusion of morphine (n = 10) or remifentanil (n = 10) for mechanical ventilation. The length of time to awaken and extubate the neonate after interrupting opioid administration was recorded. We also recorded stress (COMFORT scale), pain response [Neonatal Infant Pain Scale (NIPS)], hemodynamic and ventilatory variables as well as adverse effects secondary to infusion of the specific opioid. RESULTS: After terminating infusion, the length of time required to awaken and extubate the neonates was 18.9- and 12.1-fold longer, respectively, in the morphine group than in the remifentanil group. Both groups produced good quality sedation and analgesia as evaluated by the NIPS and COMFORT scores. No major side effects were observed. CONCLUSIONS: Our results show an interesting potential for the use of remifentanil in premature neonates. Remifentanil allowed an adequate level of sedation and analgesia as well as rapid recovery after discontinuation. However, further properly designed clinical trials are needed before it can be generally recommended.