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Sandrine Leroy,
Carla Romanello,
Vladislav Smolkin, Annick Galetto-Lacour,
Bartosz Korczowski,
David Tuerlinckx,
Carlos Rodrigo,
Vincent Gajdos,
Florence Moulin,
Paolo Pecile,
Raphaël Halevy,
Alain Gervaix,
Barbara Duhl,
Thierry Vander Borght,
Cristina Prat,
Laurence Foix-L'Hélias,
Douglas G Altman,
Dominique Gendrel,
Gérard Bréart,
Martin Chalumeau
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ABSTRACT: Urinary tract infection leads to a diagnosis of moderate or high grade (III or higher) vesicoureteral reflux in approximately 15% of children. Predicting reflux grade III or higher would make it possible to restrict cystography to high risk cases. We aimed to derive a clinical decision rule to predict vesicoureteral reflux grade III or higher in children with a first febrile urinary tract infection.
We conducted a secondary analysis of prospective series including all children with a first febrile urinary tract infection from the 8 European participating university hospitals.
A total of 494 patients (197 boys, reflux grade III or higher in 11%) were included. Procalcitonin and ureteral dilatation on ultrasound were significantly associated with reflux grade III or higher and then combined into a prediction model with an ROC AUC of 0.75 (95% CI 0.69-0.81). Given the prespecified constraint of achieving at least 85% sensitivity, our model led to the clinical decision rule, for children with a first febrile urinary tract infection cystography should be performed in cases with ureteral dilatation and serum procalcitonin level 0.17 ng/ml or higher, or without ureteral dilatation (ie ureter not visible) when serum procalcitonin level is 0.63 ng/ml or higher. The rule had 86% sensitivity (95% CI 74-93) with 47% specificity (95% CI 42-51). Internal cross-validation produced 86% sensitivity (95% CI 79-93) and 43% specificity (95% CI 39-47).
A clinical decision rule was derived to enable a selective approach to cystography in children with urinary tract infection. The rule predicts high grade vesicoureteral reflux with approximately 85% sensitivity and avoids half of the cystograms that do not find reflux grade III or higher. Further validation is needed before its widespread use.
The Journal of urology 11/2011; 187(1):265-71. · 4.02 Impact Factor
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Sandrine Leroy,
Carla Romanello, Annick Galetto-Lacour,
François Bouissou,
Anna Fernandez-Lopez,
Vladislav Smolkin,
Metin K Gurgoze,
Metin K Gurgoz,
Silvia Bressan,
Kyriaki Karavanaki, [......],
Carlos Cubells,
Raphael Halevy,
A Denizmen Aygun,
Liliana Da Dalt,
Constantinos J Stefanidis,
Thierry Vander Borght,
Sandra Bigot,
François Dubos,
Alain Gervaix,
Martin Chalumeau
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ABSTRACT: To assess the predictive value of procalcitonin, a serum inflammatory marker, in the identification of children with first urinary tract infection (UTI) who might have high-grade (≥3) vesicoureteral reflux (VUR).
We conducted a meta-analysis of individual data, including all series of children aged 1 month to 4 years with a first UTI, a procalcitonin (PCT) level measurement, cystograms, and an early dimercaptosuccinic acid scan.
Of the 152 relevant identified articles, 12 studies representing 526 patients (10% with VUR ≥3) were included. PCT level was associated with VUR ≥3 as a continuous (P = .001), and as a binary variable, with a 0.5 ng/mL preferred threshold (adjusted OR, 2.5; 95% CI, 1.1 to 5.4). The sensitivity of PCT ≥0.5 ng/mL was 83% (95% CI, 71 to 91) with 43% specificity rate (95% CI, 38 to 47). In the subgroup of children with a positive results on dimercaptosuccinic acid scan, PCT ≥0.5 ng/mL was also associated with high-grade VUR (adjusted OR, 4.8; 95% CI, 1.3 to 17.6).
We confirmed that PCT is a sensitive and validated predictor strongly associated with VUR ≥3, regardless of the presence of early renal parenchymal involvement in children with a first UTI.
The Journal of pediatrics 04/2011; 159(4):644-51.e4. · 4.02 Impact Factor
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ABSTRACT: The identification of severe bacterial infection (SBI)in children with fever without source (FWS) remains a diagnostic problem. The authors previously developed in their Swiss population a risk index score, called the Lab-score, associating three independent predictors of SBI, namely C reactive protein (CRP), procalcitonin (PCT) and urinary dipstick. The objective of this study was to validate the Lab-score in a population of children with FWS different from the derivation model.
A prospective study, conducted in Padova, on 408 children aged 7 days to 36 months with FWS was recently published. PCT, CRP, white blood cell count (WBC) and urinary dipstick were determined in all children. The Lab-score was applied to this population and the diagnostic characteristics for the detection of SBI were calculated for the Lab-score and for any single variable used in the Italian study.
For the identification of SBI, the sensitivity of a score ≥3 was 86% (95% CI 77% to 92%) and the specificity 83% (95% CI 79% to 87%). The area under the receiver operating characteristic curve for the Lab-score (0.91) was significantly superior to that of any single variable: 0.71 for WBC, 0.86 for CRP and 0.84 for PCT. The Lab-score performed better than other laboratory markers, even when applied to children of different age groups (<3 months, 3-12 months and >12 months). The results obtained in this validation set population were comparable with those of the derivation set population.
This study validated the Lab-score as a valuable tool to identify SBI in children with FWS.
Archives of Disease in Childhood 12/2010; 95(12):968-73. · 2.88 Impact Factor
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François Dubos,
Bartosz Korczowski,
Denizmen A Aygun,
Alain Martinot,
Cristina Prat, Annick Galetto-Lacour,
Juan Casado-Flores,
Erdal Taskin,
Francis Leclerc,
Carlos Rodrigo,
Alain Gervaix,
Dominique Gendrel,
Gérard Bréart,
Martin Chalumeau
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ABSTRACT: Clinical decision rules (CDRs) could be helpful to safely distinguish between bacterial and aseptic meningitis (AM).
To compare the performance of two of these CDRs for children: the Bacterial Meningitis Score (BMS) and the Meningitest.
Secondary analysis of retrospective multicentre hospital-based cohort study.
Six paediatric emergency or intensive care units of tertiary care centres in five European countries.
Consecutive children aged 29 days to 18 years presenting with acute meningitis and procalcitonin (PCT) measurement. Intervention None.
The sensitivity and specificity of the BMS (start antibiotics in case of seizure, positive cerebrospinal fluid (CSF) Gram staining, blood neutrophil count ≥10 ×10(9)/l, CSF protein level ≥80 mg/dl or CSF neutrophil count ≥1000 ×10(6)/l) and the Meningitest (start antibiotics in case of seizure, purpura, toxic appearance, PCT level ≥0.5 ng/ml, positive CSF Gram staining or CSF protein level ≥50 mg/dl) were compared using a McNemar test.
198 patients (mean age 4.8 years) from six centres in five European countries were included; 96 had bacterial meningitis. The BMS and Meningitest both showed 100% sensitivity (95% CI 96% to 100%). The BMS had a significantly higher specificity (52%, 95% CI 42% to 62% vs 36%, 95% CI 27% to 46%; p<10(-)8).
The Meningitest and the BMS were both 100% sensitive. This result provides level II evidence for the sensitivity of both rules, which can be used cautiously. However, use of the BMS could safely avoid significantly more unnecessary antibiotic treatments for children with AM than can the Meningitest in this population.
Archives of Disease in Childhood 12/2010; 95(12):963-7. · 2.88 Impact Factor
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ABSTRACT: For decades, many investigators have attempted to identify clinical or laboratory markers that can accurately differentiate severe bacterial from self-limiting viral infections in young children with fever without source. Unfortunately, no perfect marker has been discovered so far. Many guidelines recommend white blood cell count as a screening marker in fever without source, whereas compelling evidence in the literature emphasizes the superior characteristics of C-reactive protein and procalcitonin. One way to improve predictive value is the combination of prediction rules of different tests for clinical and laboratory markers. Several clinical decision rules, reviewed in this article, have been suggested but seem to be difficult to implement in practice due to their complexity. Recently, procalcitonin, C-reactive protein and urinary dipstick were combined in a simple risk index score that displayed promising predictive value in severe bacterial infections in children. Ultimately, impact analyses still have to be performed to show improved quality of care in this setting.
Expert Review of Anticancer Therapy 11/2010; 8(11):1231-7. · 3.28 Impact Factor
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ABSTRACT: The aetiological diagnosis of community-acquired pneumonia (CAP) is challenging in children, and serological markers would be useful surrogates for epidemiological studies of pneumococcal CAP. We compared the use of anti-pneumolysin (Ply) antibody alone or with four additional pneumococcal surface proteins (PSPs) (pneumococcal histidine triad D (PhtD), pneumococcal histidine triad E (PhtE), LytB, and pneumococcal choline-binding protein A (PcpA)) as serological probes in children hospitalized with CAP. Recent pneumococcal exposure (positive blood culture for Streptococcus pneumoniae, Ply(+) blood PCR finding, and PSP seroresponse) was predefined as supporting the diagnosis of presumed pneumococcal CAP (P-CAP). Twenty-three of 75 (31%) children with CAP (mean age 33.7 months) had a Ply(+) PCR finding and/or a ≥ 2-fold increase of antibodies. Adding seroresponses to four PSPs identified 12 additional patients (35/75, 45%), increasing the sensitivity of the diagnosis of P-CAP from 0.44 (Ply alone) to 0.94. Convalescent anti-Ply and anti-PhtD antibody titres were significantly higher in P-CAP than in non P-CAP patients (446 vs. 169 ELISA Units (EU)/mL, p 0.031, and 189 vs. 66 EU/mL, p 0.044), confirming recent exposure. Acute anti-PcpA titres were three-fold lower (71 vs. 286 EU/mL, p <0.001) in P-CAP children. Regression analyses confirmed a low level of acute PcpA antibodies as the only independent predictor (p 0.002) of P-CAP. Novel PSPs facilitate the demonstration of recent pneumococcal exposure in CAP children. Low anti-PcpA antibody titres at admission distinguished children with P-CAP from those with CAP with a non-pneumococcal origin.
Clinical Microbiology and Infection 10/2010; 17(8):1232-8. · 4.54 Impact Factor
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New England Journal of Medicine 09/2010; 363(14):e19. · 53.30 Impact Factor
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ABSTRACT: Rotavirus gastroenteritis (RV GE) is a leading cause of diarrhoea in young children. The purpose of this epidemiological surveillance was to measure the disease burden of RV GE among children <5 years of age in two regions of Switzerland, Geneva and Lucerne. One hospital and four paediatricians participated per region. The surveillance lasted from December 2006 to June 2007. The population denominator for calculation of the RV GE incidence rate was the average of the overall study population <5 years of age under surveillance during the surveillance period. At the study sites, 513 children with GE were presented. Stool sample was collected and examined in 341 cases, of which 130 were RV positive (38.1%). Informed consent to participate in the study was obtained for 113 RV positive subjects. The overall RV GE incidence rate was 0.97% in Lucerne [lower incidence interval (LCI), 0.71%; upper incidence interval (UCI), 1.2%] compared with 0.65 and in Geneva (LCI, 0.50%; UCI, 0.81%). Disease severity assessments using the Vescari score showed that the RV GE episodes were more severe in Lucerne than in Geneva (14.05 +/- 3.05 vs 12.85 +/- 2.87), which was confirmed by a higher hospitalisation rate in Lucerne at the study visit (82.9% vs 23.6%). More children had fever in Geneva than in Lucerne (42.9% vs 26.8%), and more children were hospitalised during the follow-up period in Geneva than in Lucerne (14.5% vs 2.5%). Genotyping of RV positive stool samples revealed that both G1 and P8 were the most prevalent types in both regions. There was a statistically significant difference in the distribution frequency of G1 between the two regions (p = 0.039). Assessment of health economic data confirmed the economic burden of RV GE episodes. In conclusion, RV GE episodes are a health burden as well as an economic burden also for the children in a developed country such as Switzerland.
European Journal of Pediatrics 09/2009; 169(3):319-25. · 1.88 Impact Factor
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ABSTRACT: Community-acquired pneumonia (CAP) is a major cause of death in developing countries and of morbidity in developed countries. The objective of the study was to define the causative agents among children hospitalized for CAP defined by WHO guidelines and to correlate etiology with clinical severity and surrogate markers. Investigations included an extensive etiological workup. A potential causative agent was detected in 86% of the 99 enrolled patients, with evidence of bacterial (53%), viral (67%), and mixed (33%) infections. Streptococcus pneumoniae was accounted for in 46% of CAP. Dehydration was the only clinical sign associated with bacterial pneumonia. CRP and PCT were significantly higher in bacterial infections. Increasing the number of diagnostic tests identifies potential causes of CAP in up to 86% of children, indicating a high prevalence of viruses and frequent co-infections. The high proportion of pneumococcal infections re-emphasizes the importance of pneumococcal immunization.
European Journal of Pediatrics 03/2009; 168(12):1429-36. · 1.88 Impact Factor
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François Dubos,
Bartosz Korczowski,
Denizmen A Aygun,
Alain Martinot,
Cristina Prat, Annick Galetto-Lacour,
Juan Casado-Flores,
Erdal Taskin,
Francis Leclerc,
Carlos Rodrigo,
Alain Gervaix,
Sandrine Leroy,
Dominique Gendrel,
Gérard Bréart,
Martin Chalumeau
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ABSTRACT: To validate procalcitonin (PCT) level as the best biological marker to distinguish between bacterial and aseptic meningitis in children in the emergency department.
Secondary analysis of retrospective multicenter hospital-based cohort studies.
Six pediatric emergency or intensive care units of tertiary care centers in 5 European countries.
Consecutive children aged 29 days to 18 years with acute meningitis.
Univariate analysis and meta-analysis to compare the performance of blood parameters (PCT level, C-reactive protein level, white blood cell count, and neutrophil count) and cerebrospinal fluid parameters (protein level, glucose level, white blood cell count, and neutrophil count) quickly available in the emergency department to distinguish early on between bacterial and aseptic meningitis.
Of 198 patients analyzed, 96 had bacterial meningitis. Sensitivity of cerebrospinal fluid Gram staining was 75%. The PCT level had significantly better results than the other markers for area under the receiver operating characteristic curve (0.98; 95% confidence interval, 0.95-0.99; P = .001). At a 0.5-ng/mL threshold, PCT level had 99% sensitivity (95% confidence interval, 97%-100%) and 83% specificity (95% confidence interval, 76%-90%) for distinguishing between bacterial and aseptic meningitis. The diagnostic odds ratio between high PCT level and bacterial meningitis was 139 (95% confidence interval, 39-498), without significant heterogeneity between centers.
The PCT level is a strong predictor for distinguishing between bacterial and aseptic meningitis in children in the emergency department. Its combination with other parameters in an effective clinical decision rule could be helpful.
Archives of pediatrics & adolescent medicine 01/2009; 162(12):1157-63. · 3.73 Impact Factor
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ABSTRACT: The objective of the study was to develop a simple clinical tool to identify serious bacterial infection (SBI) in children with fever without a source. For each child, a clinical assessment, a white blood cell count, a urine analysis, a determination of C-reactive protein, procalcitonin, and appropriate cultures were performed. Two hundred two children were studied of whom 54 (27%) had SBI. In the multivariate analysis, only procalcitonin [odds ratio (OR): 37.6], C-reactive protein (OR: 7.8), and urine dipstick (OR: 23.2) remained significantly associated with SBI. The sensitivity of the score for the identification of SBI was 94% and the specificity 81%. In the validation set the sensitivity of the score was 94% and the specificity 78%.
The Pediatric Infectious Disease Journal 08/2008; 27(7):654-6. · 3.58 Impact Factor
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Sandrine Leroy,
Carla Romanello, Annick Galetto-Lacour,
Vladislav Smolkin,
Bartosz Korczowski,
Carlos Rodrigo,
David Tuerlinckx,
Vincent Gajdos,
Florence Moulin,
Marzia Contardo,
Alain Gervaix,
Raphaël Halevy,
Barbara Duhl,
Cristina Prat,
Thierry Vander Borght,
Laurence Foix-l'Hélias,
François Dubos,
Dominique Gendrel,
Gérard Bréart,
Martin Chalumeau
[show abstract]
[hide abstract]
ABSTRACT: To validate high serum procalcitonin (PCT) as a predictor of vesicoureteral reflux (VUR) in children with a first febrile urinary tract infection (UTI).
This secondary analysis of prospective hospital-based cohort studies included children ages 1 month to 4 years with a first febrile UTI.
Of the 398 patients included in 8 centers in 7 European countries, 25% had VUR. The median PCT concentration was significantly higher in children with VUR than in those without: 1.6 versus 0.7 ng/mL (P = 10(-4)). High PCT (> or =0.5 ng/mL) was associated with VUR (OR: 2.3; 95% CI, 1.3 to 3.9; P = 10(-3)). After adjustment for all cofactors, the association remained significant (OR: 2.5; 95% CI, 1.4 to 4.4; P = 10(-3)). The strength of the relation increased with the grade of reflux (P = 10(-5)). The sensitivity of procalcitonin was 75% (95% CI, 66 to 83) for all-grade VUR and 100% (95% CI, 81 to 100) for grade > or =4 VUR, both with 43% specificity (95% CI, 37 to 48).
High PCT is a strong, independent and now validated predictor of VUR that can be used to identify low-risk patients and thus avoid one third of the unnecessary cystourethrographies in children with a first febrile UTI.
The Journal of pediatrics 01/2007; 150(1):89-95. · 4.02 Impact Factor
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ABSTRACT: To assess the value of bedside tests for predicting the occurrence of severe bacterial infections (SBIs) in children with fever without source.
We conducted a prospective study of 99 children, aged 7 days to 36 months, who were seen for fever >38 degrees C and no localizing sign of infection at the emergency department of the University Children's Hospital of Geneva. Blood procalcitonin (PCT), C-reactive protein (CRP), and interleukin-6 (IL-6) values were determined using rapid tests and were compared with the total white blood cell (WBC) count with differential and clinical score. Specificity, sensitivity, predictive values, and multilevel likelihood ratios (LRs) with posttest probabilities of disease were calculated.
Twenty-nine (29%) children received a diagnosis of having an SBI. PCT had the best sensitivity (93%) and negative predictive value (96%). Band count had the best specificity (93%), but its positive predictive value was only 38%. Multilevel LRs revealed that a PCT concentration <0.5 ng/mL (LR: 0.093) almost ruled out SBI (posttest probability of disease: 3.7%) in 54 (54%) subjects, whereas a value >2 ng/mL (LR: 5.2) increased the probability of SBI to 68% in 19 (19%) children. For CRP, values <40 mg/L (LR: 0.263) and >100 mg/L (LR: 14.483) generated posttest probabilities for SBI of 9.7% (61 subjects) and 86.5% (14 subjects), respectively. For WBC count, the posttest probabilities of SBI were modestly changed from the pretest prevalence.
PCT and CRP performed better than IL-6, WBC, and/or band count in predicting the occurrence of SBI. PCT and CRP bedside tests may be useful tools for emergency and private practice doctors and should be considered in the initial work-up of children with fever without source.
PEDIATRICS 11/2003; 112(5):1054-60. · 4.47 Impact Factor
