Risk of autoimmune diseases and human papilloma virus (HPV) vaccines: Six years of case-referent surveillance.

BACKGROUND: Safety of HPV vaccines is still in question due to reports of autoimmune diseases (ADs) following HPV immunization. OBJECTIVES: To assess the risk of ADs associated with HPV vaccination of female adolescents/young adults in France. METHODS: Systematic prospective case-referent study conducted to assess the risks associated with real-life use of HPV vaccines. Cases were female 11-25 years old with incident ADs [central demyelination/multiple sclerosis (CD/MS), connective tissue disease (CTD), Guillain-Barré syndrome (GBS), type-1 diabetes (T1D), autoimmune thyroiditis (AT), and idiopathic thrombocytopenic purpura (ITP)]. Cases were consecutively and prospectively identified at specialized centers across France (2008-2014) and individually matched by age and place of residence to referents recruited in general practice. Risk was computed using multivariate conditional logistic regression models adjusted for family history of ADs, living in France (north/south), co-medications and co-vaccinations. RESULTS: With a total of 478 definite cases matched to 1869 referents, all ADs combined were negatively associated to HPV vaccination with an adjusted odds ratio of 0.58 (95% confidence interval: 0.41-0.83). Similar results were obtained for CD/MS, AT, CT, and T1D, the last two not reaching statistical significance. No association was found for ITP and GBS. Sensitivity analyses combining definite and possible cases with secondary time window showed similar results. CONCLUSION: Exposure to HPV vaccines was not associated with an increased risk of ADs within the time period studied. Results were robust to case definitions and time windows of exposure. Continued active surveillance is needed to confirm this finding for individual ADs.

Prediction of moderate and high grade vesicoureteral reflux after a first febrile urinary tract infection in children: construction and internal validation of a clinical decision rule.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Adverse reactions and drug-drug interactions in the management of women with postmenopausal osteoporosis.

The pharmacological management of disease should involve consideration of the balance between the beneficial effects of treatment on outcome and the probability of adverse effects. The aim of this review is to explore the risk of adverse drug reactions and drug-drug interactions with treatments for postmenopausal osteoporosis. We reviewed evidence for adverse reactions from regulatory documents, randomized controlled trials, pharmacovigilance surveys, and case series. Bisphosphonates are associated with gastrointestinal effects, musculoskeletal pain, and acute-phase reactions, as well as, very rarely, atrial fibrillation, atypical fracture, delayed fracture healing, osteonecrosis of the jaw, hypersensitivity reactions, and renal impairment. Cutaneous effects and osteonecrosis of the jaw are of concern for denosumab (both very rare), though there are no pharmacovigilance data for this agent yet. The selective estrogen receptor modulators are associated with hot flushes, leg cramps, and, very rarely, venous thromboembolism and stroke. Strontium ranelate has been linked to hypersensitivity reactions and venous thromboembolism (both very rare) and teriparatide with headache, nausea, dizziness, and limb pain. The solidity of the evidence base depends on the frequency of the reaction, and causality is not always easy to establish for the very rare adverse reactions. Drug-drug interactions are rare. Osteoporosis treatments are generally safe and well tolerated, though they are associated with a few very rare serious adverse reactions. While these are a cause for concern, the risk should be weighed against the benefits of treatment itself, i.e., the prevention of osteoporotic fracture.

Rates of bronchopulmonary dysplasia in very preterm neonates in Europe: results from the MOSAIC cohort.

BACKGROUND: A considerable local variability in the rate of bronchopulmonary dysplasia (BPD) has been recorded previously. OBJECTIVES: The objectives of the present study were to describe regional differences in the rate of BPD in very preterm neonates from a European population-based cohort and to further delineate risk factors. METHODS: 4,185 survivors to 36 weeks' postmenstrual age of 4,984 live-born infants born at 24+0-31+6 weeks' gestation in 2003 (the MOSAIC cohort) in 10 European regions were enrolled using predefined structured questionnaires. RESULTS: Overall median gestational age of preterms without BPD was 30 weeks (range 23-31), median birth weight 1,320 g (range 490-3,150) compared with 27 weeks (23-31) and 900 g (370-2,460) in those with BPD. The region-specific crude rate of BPD ranged from 10.2% (Italian region) to 24.8% (UK Northern region). Maternal hypertension, immaturity, male gender, small for gestational age, Apgar <7 and region of care were associated with an increased incidence of BPD on multivariate analysis. CONCLUSION: A wide variability of BPD between European regions may be explained by different local practices; the strongest association however was with degree of immaturity.

Prediction of high-grade vesicoureteral reflux after pediatric urinary tract infection: external validation study of procalcitonin-based decision rule.

BACKGROUND: Predicting vesico-ureteral reflux (VUR) ≥3 at the time of the first urinary tract infection (UTI) would make it possible to restrict cystography to high-risk children. We previously derived the following clinical decision rule for that purpose: cystography should be performed in cases with ureteral dilation and a serum procalcitonin level ≥0.17 ng/mL, or without ureteral dilatation when the serum procalcitonin level ≥0.63 ng/mL. The rule yielded a 86% sensitivity with a 46% specificity. We aimed to test its reproducibility. STUDY DESIGN: A secondary analysis of prospective series of children with a first UTI. The rule was applied, and predictive ability was calculated. RESULTS: The study included 413 patients (157 boys, VUR ≥3 in 11%) from eight centers in five countries. The rule offered a 46% specificity (95% CI, 41-52), not different from the one in the derivation study. However, the sensitivity significantly decreased to 64% (95%CI, 50-76), leading to a difference of 20% (95%CI, 17-36). In all, 16 (34%) patients among the 47 with VUR ≥3 were misdiagnosed by the rule. This lack of reproducibility might result primarily from a difference between derivation and validation populations regarding inflammatory parameters (CRP, PCT); the validation set samples may have been collected earlier than for the derivation one. CONCLUSIONS: The rule built to predict VUR ≥3 had a stable specificity (ie. 46%), but a decreased sensitivity (ie. 64%) because of the time variability of PCT measurement. Some refinement may be warranted.

Hospitalization for severe bacterial infections in children after exposure to NSAIDs: a prospective adverse drug reaction reporting study.

BACKGROUND: NSAIDs are widely used to treat fever and pain in children, but their possible role in the progression of some bacterial infections is controversial. OBJECTIVE: This study was performed to analyse reported cases of severe bacterial infection associated with NSAID exposure in children admitted for this reason to a general paediatric department. METHODS: This study was based on the reporting system of hospital admissions for severe bacterial infections in children after NSAID exposure, and followed the recommendations of the European Guidelines of Pharmacovigilance for medicines used in a paediatric population. Data were prospectively collected and reported by active daily surveillance in the department from November 2002 to November 2005. RESULTS: Thirty-two cases of severe bacterial infections (cellulitis, soft tissue abscesses, parapneumonic empyema, necrotizing pneumonia, adenophlegmon [fever and a tender, warm and easily compressible neck mass] and lateral or retropharyngeal abscesses) were identified in children who had received NSAIDs, principally ibuprofen, in an exposure window of 15 days before the beginning of the signs of infection. Staphylococcus aureus, group A streptococci and Streptococcus pneumoniae were identified. Seven (22%) children required surgical treatment, and four (13%) were hospitalized in an intensive care unit. CONCLUSIONS: The frequency of hospitalization for severe bacterial infection as a possible adverse effect of NSAID use was 0.6% (95% CI 0.4, 0.9) of all admissions during the study period. The frequency of severe bacterial infections after exposure to NSAIDs was elevated (one case per month) in the department studied. Further work is necessary to confirm these findings, given the potential for recruitment and protopathic biases in our study.

Predictors of cerebral palsy in very preterm infants: the EPIPAGE prospective population-based cohort study.

AIM: The aim of this study was to assess the independent role of cerebral lesions on ultrasound scan, and several other neonatal and obstetric factors, as potential predictors of cerebral palsy (CP) in a large population-based cohort of very preterm infants. METHOD: As part of EPIPAGE, a population-based prospective cohort study, perinatal data and outcome at 5 years of age were recorded for 1812 infants born before 33 weeks of gestation in nine regions of France in 1997. RESULTS: The study group comprised 942 males (52%) and 870 females with a mean gestational age of 30 weeks (SD 2 wks; range 24-32 wks) and a mean birthweight of 1367 g (SD 393 g; range 450-2645 g). CP was diagnosed at 5 years of age in 159 infants (prevalence 9%; 95% confidence interval [CI] 7-10%), 97 males and 62 females, with a mean gestational age of 29 weeks (SD 2 wks; range 24-32 wks) and a mean birthweight of 1305 g (SD 386 g; range 500-2480 g). Among this group, 67% walked without aid, 14% walked with aid, and 19% were unable to walk. Spastic, ataxic, and dyskinetic CP accounted for 89%, 7%, and 4% of cases respectively. The prevalence of CP was 61% among infants with cystic periventricular leukomalacia, 50% in infants with intraparenchymal haemorrhage, 8% in infants with grade I intraventricular haemorrhage, and 4% in infants without a detectable cerebral lesion. After controlling for cerebral lesions and obstetric and neonatal factors, only male sex (odds ratio [OR] 1.52; 95% CI 1.03-2.25) and preterm premature rupture of membranes or preterm labour (OR 1.72; 95% CI 0.95-3.14) were predictors of the development of CP in very preterm infants. INTERPRETATION: Cerebral lesions were the most important predictor of CP in very preterm infants. In addition, infant sex and preterm premature rupture of membranes or preterm labour were also independent predictors of CP.

Changes in care and outcome of very preterm babies in the Parisian region between 1998 and 2003.

OBJECTIVE: To assess evolution in the care and health of very preterm babies between 1998 and 2003 after implementation of a regionalisation policy in France. DESIGN: Comparison of two population-based cohorts. SETTING: The Parisian region. PATIENTS: All live births at 24-31 weeks of gestation in 1997 (EPIPAGE study, n=488) and in 2003 (MOSAIC study, n=580). Interventions Implementation of regionalised perinatal networks. Main outcome measures In-hospital mortality and morbidity, including intraventricular haemorrhage (IVH) grade III and IV, cystic periventricular leucomalacia (PVL) and bronchopulmonary dysplasia (BPD). RESULTS: Over this period, babies born in level III units rose from 67% to 77% and use of antenatal corticosteroids, indicated deliveries and surfactant increased. In-hospital mortality and IVH grades III/IV declined, ORs of 0.66 (95% CI 0.46 to 0.95) and 0.27 (95% CI 0.15 to 0.47), respectively, while PVL and BPD stayed constant. The rate of very preterm babies discharged alive per 1000 total births increased by 18%, but declined for babies with severe brain lesions. CONCLUSIONS: The authors found improvements in mortality and morbidity for very preterm babies and changes in their care over a 6-year period following reinforcement of regionalisation policies.

Symptomatic pelvic organ prolapse at midlife, quality of life, and risk factors.

OBJECTIVE: To estimate quality of life, prevalence, and risk factors associated with symptomatic pelvic organ prolapse (POP) among middle-aged women. METHODS: This was a cross-sectional study. A questionnaire was mailed to 3,114 women aged 50-61 years in the GAZEL cohort; 2,640 (85%) returned it. Symptomatic POP was defined by feeling a bulge from the vagina (sometimes, often, or all the time compared with never or rarely). Quality of life was determined with the Nottingham Health Profile questionnaire. Multiple linear regression was used to examine the association between frequency of POP symptoms and the quality-of-life score. Logistic regression was used to estimate the effect of risk factors on past or present symptomatic POP (current symptoms or previous surgery for POP). RESULTS: The prevalence of symptomatic POP was 3.6% (96 of 2,640) and that of surgery for POP was 2.7% (70 of 2,640). Pelvic organ prolapse symptoms were associated with difficulty defecating, lower abdominal pain, and difficulty voiding. The frequency of POP symptoms was associated with a poorer quality-of-life score in each Nottingham Health Profile domain (physical mobility, pain, emotional reaction, social isolation, energy, and sleep). Even when we took general characteristics, medical history, and lifestyle associated with quality of life into account, the global Nottingham Health Profile score was significantly impaired by POP symptoms. Factors significantly associated with past or present symptomatic POP were high body mass index and the number of vaginal deliveries. CONCLUSION: In our population of women in their 50s, POP symptoms are associated with impaired quality of life, and the number of vaginal deliveries is a risk factor for past or present symptomatic POP.

Prolonged sedation and/or analgesia and 5-year neurodevelopment outcome in very preterm infants: results from the EPIPAGE cohort.

OBJECTIVE: To describe the long-term outcome of very preterm infants receiving prolonged sedation and/or analgesia and examine the relationship between prolonged sedation and/or analgesia and this long-term outcome. DESIGN: A prospective population-based study (Etude EPIdémiologique sur les Petits Ages GEstationnels [EPIPAGE]). To reduce bias, the propensity score method was used. SETTING: Nine regions of France. PARTICIPANTS: The study population included very preterm infants of fewer than 33 weeks' gestational age, born in 1997, who received mechanical ventilation and/or surgery. Main Exposure Prolonged exposure to sedative and/or analgesic drugs in the neonatal period, defined as exposure of more than 7 days to sedative and/or opioid drugs. MAIN OUTCOME MEASURE: Presence of moderate or severe disability at 5 years of age. RESULTS: The analysis concerns 1572 premature infants who received mechanical ventilation for whom information about exposure to prolonged sedation and/or analgesia in the neonatal period was available. A total of 115 were exposed and 1457 were not exposed. There was no significant difference between the number of patients lost to follow-up from the group of very preterm infants who were exposed to prolonged sedation and/or analgesia and the group who were not. Exposed very preterm infants had severe or moderate disability at 5 years (41/97; 42%) more often than those who were not exposed (324/1248; 26%). After adjustment for gestational age and propensity score, this association was no longer statistically significant (adjusted relative risk, 1.0; 95% confidence interval, 0.8-1.2). CONCLUSION: Prolonged sedation and/or analgesia is not associated with a poor 5-year neurological outcome after adjustment for the propensity score.

Epidemiology and treatment of painful procedures in neonates in intensive care units.

CONTEXT: Effective strategies to improve pain management in neonates require a clear understanding of the epidemiology and management of procedural pain. OBJECTIVE: To report epidemiological data on neonatal pain collected from a geographically defined region, based on direct bedside observation of neonates. DESIGN, SETTING, AND PATIENTS: Between September 2005 and January 2006, data on all painful and stressful procedures and corresponding analgesic therapy from the first 14 days of admission were prospectively collected within a 6-week period from 430 neonates admitted to tertiary care centers in the Paris region of France (11.3 millions inhabitants) for the Epidemiology of Procedural Pain in Neonates (EPIPPAIN) study. MAIN OUTCOME MEASURE: Number of procedures considered painful or stressful by health personnel and corresponding analgesic therapy. RESULTS: The mean (SD) gestational age and intensive care unit stay were 33.0 (4.6) weeks and 8.4 (4.6) calendar days, respectively. Neonates experienced 60,969 first-attempt procedures, with 42,413 (69.6%) painful and 18,556 (30.4%) stressful procedures; 11,546 supplemental attempts were performed during procedures including 10,366 (89.8%) for painful and 1180 (10.2%) for stressful procedures. Each neonate experienced a median of 115 (range, 4-613) procedures during the study period and 16 (range, 0-62) procedures per day of hospitalization. Of these, each neonate experienced a median of 75 (range, 3-364) painful procedures during the study period and 10 (range, 0-51) painful procedures per day of hospitalization. Of the 42,413 painful procedures, 2.1% were performed with pharmacological-only therapy; 18.2% with nonpharmacological-only interventions, 20.8% with pharmacological, nonpharmacological, or both types of therapy; and 79.2% without specific analgesia, and 34.2% were performed while the neonate was receiving concurrent analgesic or anesthetic infusions for other reasons. Prematurity, category of procedure, parental presence, surgery, daytime, and day of procedure after the first day of admission were associated with greater use of specific preprocedural analgesia, whereas mechanical ventilation, noninvasive ventilation and administration of nonspecific concurrent analgesia were associated with lower use of specific preprocedural analgesia. CONCLUSION: During neonatal intensive care in the Paris region, large numbers of painful and stressful procedures were performed, the majority of which were not accompanied by analgesia.

Selecting short-statured children needing growth hormone testing: derivation and validation of a clinical decision rule.

BACKGROUND: Numerous short-statured children are evaluated for growth hormone (GH) deficiency (GHD). In most patients, GH provocative tests are normal and are thus in retrospect unnecessary. METHODS: A retrospective cohort study was conducted to identify predictors of growth hormone (GH) deficiency (GHD) in children seen for short stature, and to construct a very sensitive and fairly specific predictive tool to avoid unnecessary GH provocative tests. GHD was defined by the presence of 2 GH concentration peaks < 10 ng/ml. Certain GHD was defined as GHD and viewing pituitary stalk interruption syndrome on magnetic resonance imaging. Independent predictors were identified with uni- and multi-variate analyses and then combined in a decision rule that was validated in another population. RESULTS: The initial study included 167 patients, 36 (22%) of whom had GHD, including 5 (3%) with certain GHD. Independent predictors of GHD were: growth rate < -1 DS (adjusted odds ratio: 3.2; 95% confidence interval [1.3-7.9]), IGF-I concentration < -2 DS (2.8 [1.1-7.3]) and BMI z-score > or = 0 (2.8 [1.2-6.5]). A clinical decision rule suggesting that patients be tested only if they had a growth rate < -1 DS and a IGF-I concentration < -2 DS achieved 100% sensitivity [48-100] for certain GHD and 63% [47-79] for GHD, and a specificity of 68% [60-76]. Applying this rule to the validation population (n = 40, including 13 patients with certain GHD), the sensitivity for certain GHD was 92% [76-100] and the specificity 70% [53-88]. CONCLUSION: We have derived and performed an internal validation of a highly sensitive decision rule that could safely help to avoid more than 2/3 of the unnecessary GH tests. External validation of this rule is needed before any application.

Differences in rates and short-term outcome of live births before 32 weeks of gestation in Europe in 2003: results from the MOSAIC cohort.

OBJECTIVES: Advances in perinatal medicine increased survival after very preterm birth in all countries, but comparative population-based data on these births are not readily available. This analysis contrasts the rates and short-term outcome of live births before 32 weeks of gestation in 10 European regions. METHODS: The Models of Organizing Access to Intensive Care for Very Preterm Births (MOSAIC) study collected prospective data on all very preterm births in 10 European regions covering 494,463 total live births in 2003. The analysis sample was live births between 24 and 31 weeks of gestation without lethal congenital anomalies (N = 4908). Outcomes were rates of preterm birth, in-hospital mortality, intraventricular hemorrhage grades III and IV or cystic periventricular leukomalacia and bronchopulmonary dysplasia. Mortality and morbidity rates were standardized for gestational age and gender. RESULTS: Live births between 24 and 31 weeks of gestation were 9.9 per 1000 total live births with a range from 7.6 to 13.0 in the MOSAIC regions. Standardized mortality was doubled in high versus low mortality regions (18%-20% vs 7%-9%) and differed for infants < or = 28 weeks of gestation as well as 28 to 31 weeks of gestation. Morbidity among survivors also varied (intraventricular hemorrhage/periventricular leukomalacia ranged from 2.6% to < or = 10% and bronchopulmonary dysplasia from 10.5% to 21.5%) but differed from mortality rankings. A total of 85.2 very preterm infants per 10,000 total live births were discharged from the hospital alive with a range from 64.1 to 117.1; the range was 10 to 31 per 10,000 live births for infants discharged with a diagnosis of neurologic or respiratory morbidity. CONCLUSIONS: Very preterm mortality and morbidity differed between European regions, raising questions about variability in treatment provided to these infants. Comparative follow-up studies are necessary to evaluate the impact of these differences on rates of cerebral palsy and other disabilities associated with preterm birth.

Mode of delivery and fecal incontinence at midlife: a study of 2,640 women in the Gazel cohort.

OBJECTIVE: To estimate obstetric risk factors of fecal incontinence among middle-aged women. METHODS: We conducted a mail survey of the Gazel cohort of volunteers for epidemiologic research. In 2000, a questionnaire on anal incontinence was mailed to 3,114 women who were then between the ages of 50 and 61 years; 2,640 (85%) women returned the completed questionnaire. Fecal incontinence was defined by involuntary loss of stool. Logistic regression was used to estimate the effect of obstetric and general risk factors. RESULTS: Prevalence of fecal incontinence in the past 12 months was 9.5% (250). Significant risk factors for fecal incontinence were completion of high school (adjusted odds ratio [OR] 1.5, 95% confidence interval [CI] 1.1-2.0), self-reported depression (OR 2.1, 95% CI 1.6-2.7), overweight or obesity measured by body mass index (BMI) (OR 1.5 for BMI of 25-30, 95% CI 1.1-2.0; OR 1.6 for BMI more than 30, 95% CI 1.1-2.5), surgery for urinary incontinence (OR 3.5, 95% CI 2.0-6.1), and anal surgery (OR 1.7, 95% CI 1.1-2.9). No obstetric variable (parity, mode of delivery, birth weight, episiotomy, or third-degree perineal tear) was significant. Prevalence of fecal incontinence was similar for nulliparous, primiparous, secundiparous, and multiparous women (11.3%, 9.0%, 9.0%, and 10.4%, respectively), and among parous women, it was similar for women with spontaneous vaginal, instrumental (at least one), or only cesarean deliveries (9.3%, 10.0%, and 6.6%, respectively). CONCLUSION: In our population of women in their 50s, fecal incontinence was not associated with either parity or mode of delivery.

Neonatal and 5-year outcomes after birth at 30-34 weeks of gestation.

OBJECTIVE: To evaluate the rates of in-hospital death, neonatal complications, and 5-year outcomes of infants born at 30-34 weeks of gestation. METHODS: In nine regions of France, all 2,020 stillbirths and live births at 30, 31, and 32 weeks in 1997 and all 457 births at 33 and 34 weeks in April and October 1997 were recorded. Survivors were evaluated at 5 years of age. RESULTS: Increasing gestational age from 30 to 34 weeks was associated with progressive decreases in in-hospital mortality (from 8.1% to 0.4%) and neonatal complications (respiratory distress syndrome, 43.8% to 2.6%; maternofetal infections, 7.2% to 2.6%; and severe white matter injury, 5.5% to 1.3%). Although infants at 33 and 34 weeks of gestation rarely experienced necrotizing enterocolitis, bronchopulmonary dysplasia, or nosocomial infections, they still required endotracheal ventilation, antibiotics, or parenteral nutrition. At 5 years of age, older gestational age was associated with significant decreases in rates of cerebral palsy (6.3% at 30 weeks and 0.7% at 34 weeks) and mild to severe cognitive impairments (35.3% at 30 weeks and 23.9% at 34 weeks). In singletons, preterm rupture of membranes or preterm labor carried an increased risk of cerebral palsy but not of cognitive impairment. CONCLUSION: Neonates born at 30-34 weeks experienced substantial morbidity and often required admission to neonatal intensive care units. These outcomes suggest that prolonging pregnancies beyond 34 weeks may be desirable whenever possible. Infants born at 30-34 weeks should be carefully monitored to ensure prompt detection and management of neurodevelopmental impairment.

Procalcitonin to reduce the number of unnecessary cystographies in children with a urinary tract infection: a European validation study.

OBJECTIVE: To validate high serum procalcitonin (PCT) as a predictor of vesicoureteral reflux (VUR) in children with a first febrile urinary tract infection (UTI). STUDY DESIGN: This secondary analysis of prospective hospital-based cohort studies included children ages 1 month to 4 years with a first febrile UTI. RESULTS: 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). CONCLUSIONS: 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.

[Procalcitonin and prediction of vesico-ureteral reflux in pediatric urinary tract infection]. / Procalcitonine et prédiction du reflux vésico-urétéral dans l'infection urinaire de l'enfant.

An estimated 7% of girls and 2% of boys will have a urinary tract infection before 6 years of age, and between 20 and 40% of these children are diagnosed with vesicoureteral reflux. Reflux is a risk factor for recurrent infections and renal scarring, which can lead to hypertension and kidney failure. Pediatric guidelines recommend routine voiding cystourethrography, but this is a painful and expensive examination that exposes children to radiation. Reliable non invasive markers of reflux would therefore be extremely useful. Ultrasonography and clinical decision rules have poor sensitivity for vesicoureteral reflux. In contrast, the level of procalcitonin, a marker of the severity of bacterial infections, is a good predictor of cystographic findings in children with a first febrile urinary tract infection. Indeed, a procalcitonin level below 0.5 ng/ml predicted the absence of radiological reflux with a sensitivity of more than 75% in the French princeps study. This was validated by a prospective European study, in which sensitivity reached 100% for high-grade reflux. Procalcitonin assay can thus avoid voiding cystourethrography in 40 to 50% of young children with febrile urinary tract infections.

Negative impact of urinary incontinence on quality of life, a cross-sectional study among women aged 49-61 years enrolled in the GAZEL cohort.

AIMS: The aim of the study was to analyze the relations between severity of urinary incontinence (UI), defined as involuntary loss of urine considered to be a hygienic or social problem, and quality of life (QoL) among middle-aged French working women enrolled in a cohort study, while taking into account characteristics that may affect this relation. METHODS: Data came from self-administered mail questionnaires completed by 2,640 women aged 49-61 years in the GAZEL cohort of utility company employees. The analysis considered social and demographic characteristics, lifestyle, hormone status, and body mass index. We used bivariate and multivariate analysis to study the associations between UI severity (measured by SANDVIK's index) and QoL scales (Contilife, specific for UI, and the generic Nottingham Health Profile). RESULTS: The sample included 556 women (21%) with UI. QoL alterations associated with UI severity were observed for all six Contilife dimensions (daily and effort activities, self-image, emotional impact, sexuality, and well-being) and two dimensions of the NHP (pain and physical mobility). These results remain after adjustment for age, BMI, and living arrangements. CONCLUSIONS: UI affects QoL even among women from a nonclinical population, and the more severe the UI, the more harmful the effect. These results raise the question of whether UI in its severe forms should be considered a disability because of its negative effects on mobility in daily life.

Cerebral palsy among very preterm children in relation to gestational age and neonatal ultrasound abnormalities: the EPIPAGE cohort study.

OBJECTIVE: To estimate the prevalence of cerebral palsy at 2 years of age among children born very preterm, according to gestational age, infant gender, plurality, and neonatal cranial ultrasound abnormalities. METHODS: All infants born between 22 and 32 weeks of gestation in 9 regions of France in 1997 were included in this prospective, population-based, cohort study. The main outcome measure was cerebral palsy prevalence at 2 years. Of the 2364 survivors eligible for follow-up evaluation, 1954 (83%) were assessed at 2 years of age. RESULTS: Among the 1954 children assessed at 2 years, 8.2% had cerebral palsy. Bilateral spastic cerebral palsy, hemiplegia, and monoplegia accounted for 72%, 9%, and 10% of cases, respectively. Fifty percent of the children with cerebral palsy walked independently at the age of 2, 31% were unable to walk but could sit independently, and 19% could not sit (unable to maintain head and trunk control). The prevalence of cerebral palsy was 20% at 24 to 26 weeks of gestation, compared with 4% at 32 weeks. On the basis of ultrasound findings in the neonatal period, we found that 17% of children with isolated grade III intraventricular hemorrhage and 25% of children with white matter damage (ie, ventricular dilation, persistent echodensities, or cystic periventricular leukomalacia) had cerebral palsy, compared with 4% of children with normal ultrasound scans. CONCLUSIONS: Despite recent improvements in survival rates, cerebral palsy remains highly prevalent among very preterm children. Severe cranial ultrasound abnormalities predict motor disability strongly, but one third of infants with cerebral palsy had no ultrasound abnormalities.

Identification of women at increased risk of osteoporosis: no need to use different screening tools at different ages.

OBJECTIVES: To assess and compare various approaches for selecting women for a bone mineral density (BMD) examination in three different age groups: (1) the most commonly recommended strategy, i.e., selection based on the presence of at least one major risk factor for osteoporosis (personal history of fracture, maternal history of hip fracture, low weight, early menopause), (2) by weight, and (3) calculation of an individual risk score based on the predictive equation (logistic regression model) including the factors most predictive of osteoporosis in each age group. METHODS: Data from three population-based samples of postmenopausal women of different ages 60-70 years (n=399), 70-80 years (n=392), and 80 years or older (n=3628). Within each age group, the value of these different approaches was primarily assessed in terms of their discriminant value (sensitivity and positive predictive value (PPV)) for osteoporosis. Other women besides osteoporotic women might also be considered at high risk of fracture (and hence treated), in particular osteopenic women (T-score<-1.5) with multiple risk factors for fracture. Hence, we also estimated and compared the overall number of selected women who might be considered at high risk of fracture after BMD testing, according to selection criteria. RESULTS: In each age group and classifying a similar percentage of women at high risk, use of weight as a tool for identifying osteoporotic women has a higher sensitivity and PPV than the currently recommended approach. Increasing the cutoff for weight increases sensitivity. However, identifying the majority (around 80%) of all osteoporotic women requires testing more than half the population. Combining weight with other factors into more complex risk scores usually does not significantly improve the discriminant value of the assessment. When similar percentages of women are selected, more women with osteopenia and multiple risk factors are identified when selection is based on usual referral criteria. However, since more osteoporotic women are identified after selection by weight (higher PPV for osteoporosis), the overall number of women who might be considered at high risk of fracture after BMD testing is higher after selection by weight. CONCLUSIONS: In each age group considered, selecting women for BMD testing based on weight is the simplest and most effective screening method for identifying osteoporotic women as well as other subgroups of women who might also be considered to be at high risk of fracture.