Urine flow acceleration in healthy children: A retrospective cohort study.

AIMS: To establish normal reference values of urine flow acceleration (Qacc ) in healthy children, as there is a lack of nomograms for normative reference values of Qacc by voided volumes in the pediatric population so far. Qacc might be an early indicator of autonomic neuropathy in children and adolescents. METHODS: Data were retrospectively collected from healthy children who underwent uroflowmetry between 1990 and 1992. Exclusion criteria were voided volume less than 20 ml, and postvoid residual more than 15%. Baseline characteristics and uroflowmetry parameters were collected from girls and boys aged between 6 and 18 years. Voided volume, voiding time, time to maximum flow rate, and maximum and average flow rates of urine were measured, and Qacc was calculated. Postvoid bladder diameter was measured by ultrasonography and converted to volume. RESULTS: Uroflowmetry parameters of 208 children (≤18 years old, 45.2% girls, mean age 9.68 ± 3.09 years) who performed 404 micturition were analyzed. Median voided volume, voiding time, time to Qmax , Qave , Qmax , Qacc , and postvoid residual volume were 130 [20-460] ml, 10 [3-56] s, 3 [1-14] s, 11.7 [2.5-36.6] ml/s, 20.5 [5-50] ml/s, 6 [0.81-25] ml/s2 , and 1.83 [0-38.62] ml, respectively. Qacc nomograms were given in centile forms for girls and boys separately, which show an inversely proportional correlation between voided volumes. CONCLUSIONS: These are the first nomograms for normative reference values of Qacc in the pediatric population (girls and boys separately) by voided volumes in centile forms. These may be useful to interpret abnormal Qacc values and diagnose lower urinary tract diseases over a wide range of voided volumes.

Urodynamics in Early Diagnosis of Diabetic Bladder Dysfunction in Women: A Systematic Review and Meta-Analysis.

BACKGROUND Urodynamics can detect subtle voiding changes before cystopathy symptoms manifest. The aim of the present study was to assess urodynamic changes in diabetic women. MATERIAL AND METHODS A systematic search was performed on 04 November 2021 to identify studies reporting urodynamic parameters in diabetic women. Data were analyzed in a single-arm meta-analysis due to lack of sufficient studies with direct comparisons to healthy women. For data synthesis, a random-effects model with restricted maximum-likelihood estimation was applied. The calculated effect sizes were visualized in forest plots. Statistical heterogeneity was assessed using the I² measure and the χ² test. The risk of bias was assessed using the QUIPS tool. PROSPERO ID: CRD42021256275. RESULTS Out of 1750 records, 10 studies were used in the analysis (n=2342 diabetic women). Pooled event rates showed that mean voided volume was 288.21 mL [95% confidence interval (CI): 217.35-359.06, I²=98%], mean postvoid residual volume was 93.67 mL [95% CI: 31.35-155.99, I²=100%], mean Qmax was 18.80 mL/sec [95% CI: 15.27-22.33, I²=99%], mean PdetQmax is 30.13 cmH2O [95% CI: 25.53-34.73, I²=90%], mean first sensation of bladder filling was 178.66 mL [95% CI: 150.59-206.72, I²=97%], and mean cystometric capacity was 480.41 mL [95% CI: 409.32-551.50, I²=98%] in diabetic women. CONCLUSIONS Pooled results indicate that diabetic women tend to have a smaller voided volume, slower Qmax and PdetQmax, larger postvoid residual, and higher first sensation of bladder filling and cystometric capacity compared to the general female population.

INvesTigating the Abnormality of detrusor ConTractility by uroflowmetry in diabetic children (INTACT Trial): protocol of a prospective, observational study.

INTRODUCTION: Bladder emptying abnormalities and cardiovascular autonomic dysfunction are manifestations of autonomic dysfunction in people with diabetes mellitus (DM), which are major causes of morbidity and mortality. Since they can reduce the quality of life, they are urgent to be addressed before resulting in complications. As uroflowmetry might determine autonomic neuropathy earlier than cardiovascular autonomic dysfunction symptoms occur, our aim is to detect early abnormalities in bladder muscle function in children with DM. We investigate the diagnostic accuracy of uroflowmetry. As a secondary aim, we compare the prevalence of uroflowmetry abnormalities to the appearance of measures of cardiovascular autonomic neuropathy. Finally, as an ancillary study, we examine the association of uroflowmetry with the appearance of peripheral neuropathy. These three aims, we feel, will put our results regarding uroflowmetry into an overall context of nerve disease early in the course of type 1 DM. To our knowledge, such an approach has heretofore not been performed. METHODS AND ANALYSIS: This will be a prospective, observational, single-centre clinical study. Patients with DM fulfilling the inclusion criteria and healthy controls will have uroflowmetry examination, cardiovascular autonomic dysfunction tests (heart rate response to deep breathing, to Valsalva manoeuvre, blood pressure and heart rate response to standing up, and to sustained handgrip) and nerve conduction test. The autonomic nervous system function will be examined by the reproducible and standardised cardiovascular reflex tests described by Ewing et al. During the examination, electrocardiogram (ECG) and blood pressure values will be recorded continuously. Heart rate response to deep inspiration will be executed to investigate the parasympathetic nervous system. Peripheral neuropathy will be evaluated by nerve conduction test. After a pilot period, when the first 50 diabetic and 50 healthy children will be assessed, sample size calculation will be carried out. The primary objective of this trial is to evaluate the diagnostic accuracy (sensitivity, specificity, positive and negative predictive value) of uroflowmetry. To do so, we compare uroflowmetry to the gold standard neuropathy tests, which are cardiovascular autonomic dysfunction tests (heart rate response to deep breathing, to Valsalva manoeuvre, blood pressure and heart rate response to standing up and to sustained handgrip). ETHICS AND DISSEMINATION: Ethics approval was obtained from the Scientific and Research Ethics Committee of the Heim Pál National Paediatric Institute in Budapest, Hungary (registration number KUT-37/2021). Results will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT05247840.

Differential Diagnostic Challenges in the COVID-19 Pandemic: Renal Abscess After SARS-CoV-2 Infection in a Young Adolescent.

BACKGROUND Prolonged fever in pediatric patients is often a diagnostic challenge. Clinicians tend to associate prolonged fever with COVID-19-related diseases in patients with a history of SARS-CoV-2 infection. Here we present a patient who was admitted with a clinical suspicion of multi-inflammatory syndrome in children (MIS-C) and was finally diagnosed with a renal abscess. CASE REPORT A 16-year-old girl with prolonged fever, bilateral non-purulent conjunctivitis, weight loss, muscle pain, general malaise, cough, and yellow sputum was admitted to Heim Pál National Pediatric Institute, Budapest, Hungary. She had proven SARS-CoV-2 infection 3 weeks prior to admission. Although inflammatory markers were elevated, repeated urine analyses, aerobic and anaerobic urine cultures, hemoculture, chest X-ray, and otorhinolaryngology examinations were negative. Based on clinical and laboratory criteria, the diagnosis of MIS-C was eventually ruled out. Abdominal ultrasound revealed a 17×20×15 mm simplex cyst at the edge of the parenchyma in the upper third of the left kidney. Magnetic resonance imaging was performed, showing a multi-compartment, septated, thick-walled parenchymal lesion of 50×40×52 mm in the upper pole of the right kidney, which showed signal characteristics of an abscess, and 20×16 mm and 8 mm lesions in the upper pole of the left kidney, which appeared to be cysts. After being unresponsive to intravenous wide-spectrum antibiotic therapy (meropenem 2 g tid for 5 days), surgical intervention was needed to remove the abscess. CONCLUSIONS This case demonstrates that during the COVID-19 pandemic, besides the obvious post-COVID etiology, other life-threatening conditions should be investigated in the first line.

Association of Body Mass Index With Clinical Outcomes in Patients With Cystic Fibrosis: A Systematic Review and Meta-analysis.

IMPORTANCE: The prevalence of overweight (body mass index [BMI] = 25-29.9 [calculated as weight in kilograms divided by height in meters squared]) and obesity (BMI ≥30) is increasing among patients with cystic fibrosis (CF). However, it is unclear whether there is a benefit associated with increasing weight compared with the reference range (ie, normal) in CF. OBJECTIVE: To evaluate the association of altered BMI or body composition and clinical outcomes in patients with CF. DATA SOURCES: For this systematic review and meta-analysis, the literature search was conducted November 2, 2020, of 3 databases: MEDLINE (via PubMed), Embase, and Cochrane Central Register of Controlled Trials. STUDY SELECTION: Patients older than 2 years diagnosed with CF with altered body composition or BMI were compared with patients having the measured parameters within the reference ranges. Records were selected by title, abstract, and full text; disagreements were resolved by consensus. Cohort studies and conference abstracts were eligible; articles with no original data and case reports were excluded. DATA EXTRACTION AND SYNTHESIS: Two authors independently extracted data, which were validated by a third author. Studies containing insufficient poolable numerical data were included in the qualitative analysis. A random-effects model was applied in all analyses. MAIN OUTCOMES AND MEASURES: Pulmonary function, exocrine pancreatic insufficiency (PI), and CF-related diabetes (CFRD) were investigated as primary outcomes. Odds ratios (ORs) or weighted mean differences (WMDs) with 95% CIs were calculated. The hypothesis was formulated before data collection. RESULTS: Of 10 524 records identified, 61 met the selection criteria and were included in the qualitative analysis. Of these, 17 studies were included in the quantitative synthesis. Altogether, 9114 patients were included in the systematic review and meta-analysis. Overweight (WMD, -8.36%; 95% CI, -12.74% to -3.97%) and obesity (WMD, -12.06%; 95% CI, -23.91% to -0.22%) were associated with higher forced expiratory volume in the first second of expiration compared with normal weight. The odds for CFRD and PI were more likely in patients of normal weight (OR, 1.49; 95% CI, 1.10 to 2.00) than in those who were overweight (OR, 4.40; 95% CI, 3.00 to 6.45). High heterogeneity was shown in the analysis of pulmonary function (I2 = 46.7%-85.9%). CONCLUSIONS AND RELEVANCE: The findings of this systematic review and meta-analysis suggest that the currently recommended target BMI in patients with CF should be reconsidered. Studies with long-term follow-up are necessary to assess the possible adverse effects of higher BMI or higher fat mass in patients with CF.

Inflammatory Biomarkers Are Inaccurate Indicators of Bacterial Infection on Admission in Patients With Acute Exacerbation of Chronic Obstructive Pulmonary Disease-A Systematic Review and Diagnostic Accuracy Network Meta-Analysis.

Introduction: The value of inflammatory biomarkers in the diagnosis of bacterial infection induced acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is currently unclear. Our objective was to investigate the diagnostic accuracy of on-admission inflammatory biomarkers in differentiating bacterial origin in AECOPD. Methods: Systematic literature search was performed to include cross-sectional studies on AECOPD patients with microbiological culture results as gold standard, and at least one on-admission inflammatory biomarker determined from serum: C-reactive protein (CRP), procalcitonin (PCT), neutrophil/lymphocyte ratio, eosinophil percentage, CD64index; or sputum: neutrophil elastase, tumor necrosis factor alfa, interleukin-1-beta (IL-1b), interleukin-8, sputum color, as index tests. We ranked index tests by superiority indices in a network meta-analysis and also calculated pooled sensitivity and specificity. Results: Altogether, 21 eligible articles reported data on 2,608 AECOPD patients (44% bacterial). Out of the 14 index tests, sputum IL-1b showed the highest diagnostic performance with a pooled sensitivity of 74% (CI: 26-97%) and specificity of 65% (CI: 19-93%). Pooled sensitivity for CRP and PCT were: 67% (CI: 54-77%) and 54% (CI: 39-69%); specificity 62% (CI: 52-71%) and 71% (CI: 59-79%), respectively. Conclusion: Admission inflammatory biomarkers are inaccurate indicators of bacterial infection in AECOPD. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/#myprospero, identifier: 42020161301.

Increased Prevalence of Celiac Disease in Patients with Cystic Fibrosis: A Systematic Review and Meta-Analysis.

OBJECTIVES: Immune regulation seems to be altered in cystic fibrosis (CF), thus potentially predisposing patients to developing autoimmune diseases (AID). In this meta-analysis, we aimed to evaluate the prevalence of celiac disease (CeD) among CF patients as by far the most commonly reported autoimmune disease in this population and, secondly, to review the observations on other, less frequently studied autoimmune diseases. METHODS: We conducted a systematic literature search for studies that discussed AIDs among CF patients. Following standard selection and data collection, we calculated pooled raw prevalence with 95% confidence intervals (CI) for biopsy-verified CeD and seropositivity. RESULTS: Out of the 21 eligible studies, 15 reported on CeD. Pooled prevalence of biopsy-verified CeD was 1.8% (CI 1.1-2.7%) according to a homogeneous dataset from six prospective, consecutive screening studies, while it proved to be 2.3% (CI 1.1-4.7%) according to a heterogeneous dataset from the other studies. Tissue transglutaminase IgA positivity was detected in 4.5% of CF cases (CI 2.8-6.9%), while tissue transglutaminase IgA-endomysial antibody IgA double positivity was found in 2.4% of them (CI 1.5-3.9%). Findings on other AIDs were strongly limited. CONCLUSIONS: The pooled prevalence of CeD in CF seemed to be more than twice as high compared to the global prevalence; therefore, routine screening of CeD could be considered in CF.

Non-invasive Diagnostic Tests in Cystic Fibrosis-Related Liver Disease: A Diagnostic Test Accuracy Network Meta-Analysis.

Background and Aims: Cystic fibrosis-related liver disease (CFLD) is one of the leading causes of morbidity and mortality in cystic fibrosis (CF). Several non-invasive diagnostic methods have been proposed as screening tools for CFLD. Our aim was to rank all available non-invasive modalities for diagnostic performance. Methods: A systematic search was performed in five medical databases to find studies which reported on any single or composite non-invasive diagnostic test (as an index test) compared to the Debray, the EuroCare or the Colombo criteria (as a reference standard). Ranking was carried out with a Bayesian diagnostic test accuracy network meta-analysis based on superiority indices, calculated for pooled sensitivity (Se) and specificity (Sp) with a 95% confidence interval (CI). The study was registered under CRD42020155846 in PROSPERO. Results: Fifteen studies with 15 index tests and a combination of them were included. The New criteria proposed by Koh et al. - which represent a composite diagnostic definition for CFLD including liver biochemistry, ultrasonography, transient elastography and fibrosis markers-had the best performance for detecting CFLD (Se:94%[CI:58-100], Sp:72%[CI:52-84]); while transient elastography (Se:65%[CI:56-74], Sp:88%[CI:84-91]) and a combination of it with a tissue inhibitor of metalloproteinase-4 measurement (Se:78%[CI:30-100], Sp:64%[CI:18-95%]) proved to be the second and third best options, respectively. In the imaging techniques subgroup, transient elastography (Se:66%[CI:57-72], Sp:88%[CI:85-91%]), acoustic radiation force impulse in the right lobe (Se:54%[CI:33-74], Sp:88%[CI:66-96]) and that in the left lobe (Se:55%[CI:23-81], Sp:82%[CI:50-95]) were ranked the highest. Comparing biochemical markers/fibrosis indices, the measurement of the Forns index (Se:72%[CI:25-99], Sp:63%[CI:16-94]), the aspartate aminotransferase-to-platelet ratio (Se:55%[CI:41-68], Sp:83%[CI:66-89]) and alkaline phosphatase (Se:63%[CI:18-93], Sp:64%[CI:19-95]) were ranked the highest. Conclusion: The New criteria show the best diagnostic performance. In clinical practice, transient elastography seems to be a simple, cheap and non-invasive tool, outperforming imaging, biochemical and fibrosis tests for detecting CFLD. Further studies are needed to validate our findings.

Systematic review with meta-analysis: the effects of immunomodulator or biological withdrawal from mono- or combination therapy in inflammatory bowel disease.

BACKGROUND: Withdrawal of treatment is a common therapeutic problem in patients with long-standing remission of inflammatory bowel disease. AIMS: To evaluate the relapse rate in patients with quiescent inflammatory bowel disease after cessation of biologic or immunomodulator therapy. METHODS: We searched five databases for studies evaluating disease relapse after withdrawal of monotherapy or a drug from combination therapy in Crohn's disease or ulcerative colitis. In meta-analysis, risk ratios (RR) were calculated with 95% confidence intervals (CI). RESULTS: Ten randomised controlled trials (587 patients) were included in the meta-analysis, and another nine studies in systematic review. Withdrawal of immunomodulator monotherapy resulted in a significantly higher risk of relapse within 24 months of follow-up compared to ongoing therapy in Crohn's disease, but not in ulcerative colitis (RR = 2.06, CI: 1.53-2.77 and RR = 1.39, CI: 0.85-2.26, respectively). Trial sequential analysis indicated that further studies with similar design are unlikely to change the significant association on relapse rates after withdrawing immunomodulator monotherapy in patients with Crohn's disease. Discontinuation of an immunomodulator from combination with biologics did not show a higher risk of relapse than continuation of both drugs (RR = 1.30, CI: 0.81-2.08). The relapse rate increased after withdrawal of biologic monotherapy, whereas contradictory results were observed after biologic withdrawal from combination regimens. CONCLUSION: Continuing immunomodulator monotherapy should remain the preferred approach among patients with Crohn's disease, although long-term toxicity is a concern. Further randomised controlled trials are warranted in ulcerative colitis and on combination regimens including biologics.

Personalised health education against health damage of COVID-19 epidemic in the elderly Hungarian population (PROACTIVE-19): protocol of an adaptive randomised controlled clinical trial.

BACKGROUND: Early reports indicate that COVID-19 may require intensive care unit (ICU) admission in 5-26% and overall mortality can rise to 11% of the recognised cases, particularly affecting the elderly. There is a lack of evidence-based targeted pharmacological therapy for its prevention and treatment. We aim to compare the effects of a World Health Organization recommendation-based education and a personalised complex preventive lifestyle intervention package (based on the same WHO recommendation) on the outcomes of the COVID-19. METHODS: PROACTIVE-19 is a pragmatic, randomised controlled clinical trial with adaptive "sample size re-estimation" design. Hungarian population over the age of 60 years without confirmed COVID-19 will be approached to participate in a telephone health assessment and lifestyle counselling voluntarily. Volunteers will be randomised into two groups: (A) general health education and (B) personalised health education. Participants will go through questioning and recommendation in 5 fields: (1) mental health, (2) smoking habits, (3) physical activity, (4) dietary habits, and (5) alcohol consumption. Both groups A and B will receive the same line of questioning to assess habits concerning these topics. Assessment will be done weekly during the first month, every second week in the second month, then monthly. The composite primary endpoint will include the rate of ICU admission, hospital admission (longer than 48 h), and mortality in COVID-19-positive cases. The estimated sample size is 3788 subjects per study arm. The planned duration of the follow-up is a minimum of 1 year. DISCUSSION: These interventions may boost the body's cardiovascular and pulmonary reserve capacities, leading to improved resistance against the damage caused by COVID-19. Consequently, lifestyle changes can reduce the incidence of life-threatening conditions and attenuate the detrimental effects of the pandemic seriously affecting the older population. TRIAL REGISTRATION: The study has been approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (IV/2428- 2 /2020/EKU) and has been registered at clinicaltrials.gov ( NCT04321928 ) on 25 March 2020.