[Show abstract][Hide abstract] ABSTRACT: Children with sickle cell disease (SCD) have a significant vascular morbidity, especially cerebral macrovasculopathy (CV), detectable by transcranial Doppler. This study aimed to identify risk factors for CV using longitudinal biological and clinical data in a SCD newborn cohort followed at the Robert Debre Reference centre (n = 375 SS/Sβ(0) ). Median follow-up was 6·8 years (2677 patient-years). Among the 59 children presenting with CV, seven had a stroke. Overall, the incidence of CV was 2·20/100 patient-years [95% confidence interval (95% CI): 1·64-2·76] and the incidence of stroke was 0·26/100 patient-years (95% CI: 0·07-0·46). The cumulative risk of CV by age 14 years was 26·0% (95% CI: 20·0-33·3%). Risk factors for CV were assessed by a Cox model encompassing linear multivariate modelling of longitudinal quantitative variables. Years per upper-airway obstruction [Hazard ratio (HR) = 1·47; 95% CI: 1·05-2·06] or bronchial obstruction (HR = 1·76; 95% CI: 1·49-2·08) and reticulocyte count (HR = 1·82 per 50 × 10(9) /l increase; 95% CI: 1·10-3·01) were independent risk factors whereas fetal haemoglobin level (HR = 0·68 per 5% increase; 95% CI: 0·48-0·96) was protective. Alpha-thalassaemia was not protective in multivariate analysis (ancillary analysis n = 209). Specific treatment for upper or lower-airway obstruction and indirect targeting of fetal haemoglobin and reticulocyte count by hydroxycarbamide could potentially reduce the risk of CV.
Full-text · Article · Jan 2016 · British Journal of Haematology
[Show abstract][Hide abstract] ABSTRACT: Background Approximately 15 to 30% of children and adolescents suffer from daily pain persistent over more than 3 months and there is evidence supporting that the prevalence of chronic pain is steadily increasing in this population. Chronic pain is known to have a negative impact on children's development and social behaviour, leading often to severe psychological distress and physical disability. We reviewed medical literature to assess the characteristics and quality of randomized controlled trials (RCTs) on pharmacological and non-pharmacological therapies in chronic and recurrent pain in the paediatric population.
Methods We performed a systematic search of PubMed, Embase and the Cochrane Library up to March 2014. Bibliographies of relevant articles were also hand-searched. We included all RCTs that involved children and adolescents (age 0 to 18 years) and evaluated the use of a pharmacological agent or a non-pharmacological approach in the context of chronic or recurrent pain. The latter was defined as pain persisting for more than 3 months. Methodological quality was evaluated using the Cochrane Risk of Bias Tool. Two reviewers independently assessed studies for inclusion and evaluated methodological quality.
Results A total of 52 randomized controlled trials were selected and included in the analysis. The majority were conducted in single hospital institutions, with no information on study funding. Median sample size was 45 (34–57) participants. Almost 50% of the RCTs included both adults and children with a median age at inclusion of 13 years. Non-pharmacological approaches were more commonly tested whereas evaluation of pharmacological agents concerned less than 30% of RCTs. Abdominal pain and headache were the most common types of chronic pain experienced among trial participants. Overall, the methodological quality was poor and did not parallel the number of RCTs that increased over the years. The risk of bias was high or unclear in 70% of the trials.
Conclusions This is the first systematic review of RCTs conducted to evaluate pharmacological and non-pharmacological therapies in chronic and recurrent pain in children and adolescents. Although, management of pain in adults has significantly improved over the years due to the evaluation of numerous analgesic therapies, our results highlight the existing knowledge gap with regards to children and adolescents. Therapeutic strategies, in particular pharmacological agents, applied to relieve chronic or recurrent pain in children and adolescents are not evaluated through high quality RCTs. The need to improve analgesic therapy in children and adolescents with chronic pain is still unmet. We discuss possible research constraints and challenges related to this fact as well as adequate methodologies to circumvent them.
No preview · Article · Jan 2016 · Archives of Disease in Childhood
[Show abstract][Hide abstract] ABSTRACT: Background: In a context where there is an increasing demand to evaluate the outcome of bio-medical research, our work aims to develop a set of indicators to measure the impact of translational cancer research. The objective of our study was to explore the scope and issues of translational research relevant to evaluation, explore the views of researchers on the evaluation of oncological translational research, and select indicators measuring the outcomes and outputs of translational research in oncology by consensus. Methods: Semi-structured interviews amongst 23 researchers involved in translational cancer research were conducted and analysed using thematic analysis. A two-round modified Delphi survey of 35 participants with similar characteristics was then performed followed by a physical meeting. Participants rated the feasibility and validity of 60 indicators. The physical meeting was held to discuss the methodology of the new indicators. Results: The main themes emerging from the interviews included a common definition for translational research but disagreements about the exact scope and limits of this research, the importance of multidisciplinarity and collaboration for the success of translational research, the disadvantages that translational research faces in current evaluation systems, the relative lack of pertinence of existing indicators, and propositions to measure translational cancer research in terms of clinical applications and patient outcomes. A total of 35 participants took part in the first round survey and 12 in the second round. The two-round survey helped us select a set of 18 indicators, including four that seemed to be particularly adapted to measure translational cancer research impact on health service research (number of biomarkers identified, generation of clinical guidelines, citation of research in clinical guidelines, and citation of research in public health guidelines). The feedback from participants helped refine the methodology and definition of indicators not commonly used. Conclusion: Indicators need to be accepted by stakeholders under evaluation. This study helped the selection and refinement of indicators considered as the most relevant by researchers in translational cancer research. The feasibility and validity of those indicators will be tested in a scientometric study.
Full-text · Article · Dec 2015 · Health Research Policy and Systems
[Show abstract][Hide abstract] ABSTRACT: Autosomal recessive primary microcephaly results from abnormal brain development linked to proliferation defects in neural progenitors. The most frequent form, caused by ASPM mutations, is usually defined by a reduced brain volume and is associated with intellectual disability. Although many ASPM cases have now been reported, structural brain abnormalities and their link with cognitive disabilities have rarely been investigated. In this study, we used high resolution T1-weighted magnetic resonance imaging in seven patients with ASPM mutations and 39 healthy age-matched controls to quantify regional volumes, thickness, surface area, gyrification index and white matter volumes of 30 cortical regions. We observed a consistent reduction of 50% or more in the volume and surface area of all cortical regions except for the hippocampus and surrounding medial temporal structures, which were significantly less reduced. Neuropsychologic assessment indicated significant impairments of cognitive abilities. However, these impairments were associated with normal mnesic abilities, in keeping with the relative preservation of the hippocampus and medial temporal structures. These results show that, contrary to current opinion, the cortical volume and surface area of patients with ASPM mutations is reduced depending on a regionally specific fashion and their cognitive profile reflects this heterogeneity. The precise characterization of the cortical map and cognitive abilities of patients with ASPM mutations should allow developing more focused reeducative interventions well-suited to their real abilities.
[Show abstract][Hide abstract] ABSTRACT: While the incidence of diabetes mellitus (DM) during pregnancy has been steadily increasing in recent years, the link between gestational DM and respiratory outcome in neonates has not been definitely established. We asked the question whether DM status and its treatment during pregnancy could influence the risk of neonatal respiratory distress.
We studied in a large retrospective cohort the relationship between maternal DM status (non-DM, insulin-treated DM (IT-DM) and non-insulin-treated DM (NIT-DM)), and respiratory distress in term and near-term inborn singletons.
Among 18 095 singletons delivered at 34 weeks of gestation or later, 412 (2.3%) were admitted to the neonatal intensive care unit (NICU) for respiratory distress within the first hours of life. The incidence of NICU admission due to respiratory distress groups was 2.2%, 5.7% and 2.1% in the non-DM, IT-DM and NIT-DM groups, respectively. Insulin treatment of DM, together with several other perinatal factors, was associated with a significant increased risk for respiratory distress. Several markers of the severity of respiratory illness, including durations of mechanical ventilation and supplemental oxygen, and hypertrophic cardiomyopathy were also found increased following IT-DM as compared with NIT-DM. In a multivariate model, we found that IT-DM, but not NIT-DM, was significantly associated with respiratory distress independent of gestational age and caesarean section, with an incidence rate ratio of 1.44 (1.00-2.08).
This study shows that the treatment of maternal DM with insulin during pregnancy is an independent risk factor for respiratory distress in term and near-term newborns.
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
[Show abstract][Hide abstract] ABSTRACT: Background:
There is an increasing need to evaluate the production and impact of medical research produced by institutions. Many indicators exist, yet we do not have enough information about their relevance. The objective of this systematic review was (1) to identify all the indicators that could be used to measure the output and outcome of medical research carried out in institutions and (2) enlist their methodology, use, positive and negative points.
We have searched 3 databases (Pubmed, Scopus, Web of Science) using the following keywords: [Research outcome* OR research output* OR bibliometric* OR scientometric* OR scientific production] AND [indicator* OR index* OR evaluation OR metrics]. We included articles presenting, discussing or evaluating indicators measuring the scientific production of an institution. The search was conducted by two independent authors using a standardised data extraction form. For each indicator we extracted its definition, calculation, its rationale and its positive and negative points. In order to reduce bias, data extraction and analysis was performed by two independent authors.
We included 76 articles. A total of 57 indicators were identified. We have classified those indicators into 6 categories: 9 indicators of research activity, 24 indicators of scientific production and impact, 5 indicators of collaboration, 7 indicators of industrial production, 4 indicators of dissemination, 8 indicators of health service impact. The most widely discussed and described is the h-index with 31 articles discussing it.
The majority of indicators found are bibliometric indicators of scientific production and impact. Several indicators have been developed to improve the h-index. This indicator has also inspired the creation of two indicators to measure industrial production and collaboration. Several articles propose indicators measuring research impact without detailing a methodology for calculating them. Many bibliometric indicators identified have been created but have not been used or further discussed.
[Show abstract][Hide abstract] ABSTRACT: Objective To assess, in a pediatric population, the clinical characteristics and management of triiodothyronine-predominant Graves' disease (T3-P-GD), a rare condition well known in adults, but not previously described in children. Design We conducted a university hospital-based observational study. Methods All patients with GD followed for more than one year between 2003 and 2013 (n=60) were included. T3-P-GD (group I) was defined as high fT3 concentration (>8.0 pmol/l) associated with a normal fT4 concentration and undetectable TSH more than one month after the initiation of antithyroid drug (ATD) treatment. Group II contained patients with classical GD without T3-P-GD. Results Eight (13%) of the patients were found to have T3-P-GD, a median of 6.3 (3.0-10.5) months after initial diagnosis (n=4) or 2.8 (2.0-11.9) months after the first relapse after treatment discontinuation (n=4). At GD diagnosis, group I patients were more likely to be younger [6.8 (4.3-11.0) vs. 10.7 (7.2-13.7) years] and had more severe disease than group II patients, with higher serum TRAb levels: 40 (31-69) vs. 17 (8-25) IU/l, p<0.04 and with slightly higher serum fT4 [92 (64-99) vs. 63 (44-83) pmol/l] and fT3 [31 (30-46) vs. 25 (17-31) pmol/l] concentrations. During the three years following T3-P-GD diagnosis, a double dose of ATD was required and median serum fT4/fT3 ratio remained lower in group I than in group II. Conclusion Severe hyperthyroidism, with particularly high TRAb concentrations at diagnosis, may facilitate the identification of patients requiring regular serum fT3 determinations and potentially needing higher doses of ATD dosage during follow-up.
No preview · Article · Mar 2015 · European Journal of Endocrinology
[Show abstract][Hide abstract] ABSTRACT: Arthritis in children has many causes and includes septic and viral arthritis, reactive arthritis and juvenile idiopathic arthritis (JIA). We aimed to describe the different types of arthritis among children hospitalised for a first episode of arthritis.
Retrospective, descriptive case series study.
A French tertiary care centre.
Children under 16 years of age hospitalised for an arthritis episode between 1 January 2008 and 31 December 2009.
Demographic and clinical features were compared with χ(2) or Fisher's exact tests and non-parametric tests.
173 children were hospitalised for a first episode of arthritis during the study period, with a male/female ratio of 1.14. The most frequent cause of hospitalisation was septic arthritis (43.4% of cases, 69.3% of which were due to Kingella kingae and 10.7% to Staphylococcus aureus). JIA was responsible for 8.1% of cases and arthritis without any definitive diagnosis for 40.4%. Median age at diagnosis was 2.7 years (IQR 0.3-14.6) and was lower in the septic arthritis group (1.5 years; 1.1-3.4) than in the JIA group (4.7 years; 2.5-10.9) (p<0.01). Septic arthritis involved a single joint in 97.3% of cases, while JIA involved four joints in 14.3% of cases and two to four joints in 28.6% of cases (p<0.01).
Septic arthritis was the most frequent cause of arthritis in hospitalised children. Despite the increasing application of microbiological molecular methods to synovial fluid analysis, further measures are required to improve the diagnosis of arthritis of unknown cause.
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
No preview · Article · Mar 2015 · Archives of Disease in Childhood
[Show abstract][Hide abstract] ABSTRACT: Background
In addition to their effects on bone health, high doses of cholecalciferol may have beneficial non-classic effects including the reduction of incidence of type 2 diabetes mellitus, cardiovascular disease, and cancer. These pleiotropic effects have been documented in observational and experimental studies or in small intervention trials. Vitamin D insufficiency is a frequent finding in renal transplant recipients (RTRs), and this population is at risk of the previously cited complications.
The VITALE study is a prospective, multicentre, double-blind, randomized, controlled trial with two parallel groups that will include a total of 640 RTRs. RTRs with vitamin D insufficiency, defined as circulating 25-hydroxyvitamin D levels of less than 30 ng/ml (or 75 nmol/l), will be randomized between 12 and 48 months after transplantation to blinded groups to receive vitamin D3 (cholecalciferol) either at high or low dose (respectively, 100,000 UI or 12,000 UI every 2 weeks for 2 months then monthly for 22 months) with a follow-up of 2 years. The primary objective of the study is to evaluate the benefit/risk ratio of high-dose versus low-dose cholecalciferol on a composite endpoint consisting of de novo diabetes mellitus; major cardiovascular events; de novo cancer; and patient death. Secondary endpoints will include blood pressure (BP) control; echocardiography findings; the incidences of infection and acute rejection episodes; renal allograft function using estimated glomerular filtration rate; proteinuria; graft survival; bone mineral density; the incidence of fractures; and biological relevant parameters of mineral metabolism.
We previously reported that the intensive cholecalciferol treatment (100 000 IU every 2 weeks for 2 months) was safe in RTR. Using a pharmacokinetic approach, we showed that cholecalciferol 100,000 IU monthly should maintain serum 25-hydroxyvitamin D at above 30 ng/ml but below 80 ng/ml after renal transplantation. Taken together, these results are reassuring regarding the safety of the cholecalciferol doses that will be used in the VITALE study. Analysis of data collected during the VITALE study will demonstrate whether high or low-dose cholecalciferol is beneficial in RTRs with vitamin D insufficiency.
ClinicalTrials.gov Identifier: NCT01431430.
[Show abstract][Hide abstract] ABSTRACT: Objectives
To shed light on the meaning of Aspergillus-positive lower-respiratory-tract samples in non immunocompromized critically ill patients.
Multicentre matched case-control (1:5) study. We used prospectively collected data to identify risk factors for Aspergillus-positive specimens, as well as outcomes in Aspergillus-positive patients.
66 cases (5 with definite invasive pulmonary aspergillosis (IPA), 18 with probable IPA, and 43 colonisations) were matched to 330 controls. In the multivariate conditional logistic model, independent risk factors for at least one Aspergillus-positive respiratory-tract specimen were worse SAPSII at admission [OR, 1.10; 95%CI, 1.00-1.21], ARDS [OR, 2.64; 95%CI, 1.29-5.40]; long-term steroid therapy [OR, 4.77; 95%CI, 1.49-15.23]; steroid therapy started in the ICU [OR, 11.03; 95%CI, 4.40-27.67]; and bacterial infection [OR, 2.73; 95%CI, 1.37-5.42]. The risk of death, compared to the controls, was not higher in the cases overall [HR, 0.66; 95%CI, 0.41-1.08; p=0.1] or in the subgroups with definite IPA [HR, 1.60; 95%CI, 0.43-5.94; p=0.48], probable IPA [HR, 0.84; 95%CI, 0.28-2.50; p=0.76], or colonisation [HR, 0.58; 95%CI, 0.33-1.02; p=0.06]. In cases who received antifungal therapy, mortality was not lower than in untreated cases [HR, 0.67; 95%CI, 0.36-1.24; p=0.20].
In critically ill immunocompetent patients, risk factors for presence of Aspergillus in lower respiratory tract specimens are steroid therapy (either chronic or initiated in the ICU), ARDS, and high severity of the acute illness. Prospective studies are warranted to further examine these risk factors and to investigate immune functions as well as the impact of antifungal therapy on patient outcomes.
No preview · Article · Sep 2014 · Journal of Infection
[Show abstract][Hide abstract] ABSTRACT: Objectives:
To evaluate the frequency and to identify the risk factors of severe perineal lacerations and the subgroup of women exposed to the highest risk for these complications.
We conducted a case-control study in a large cohort of women for which vaginal delivery management consisted in systematic perineal support and restrictive use of mediolateral episiotomy. The case group comprised women with severe perineal lacerations while the control group comprised women without severe perineal lacerations. Maternal, labor, delivery and neonatal characteristics were analyzed in logistic regression models and a classification and regression tree (CART) was constructed.
Between 2000 and 2009, 19,442 women delivered vaginally in our centre, 88 of whom had severe perineal lacerations (0.5%). Instrumental delivery (aOR 4.17, 95% CI 2.51-6.90), nulliparity (aOR 2.58, 95% CI 1.55-4.29), persistent posterior orientation (aOR 2.24, 95% CI 1.02-4.94) and increased birth weight (aOR 1.28, 95% CI 1.03-1.60) were independent risk factors of severe perineal lacerations whereas mediolateral episiotomy had a protective effect (aOR 0.38, 95% CI 0.23-0.63). CART identified instrumental delivery of neonates smaller than 4500 g in persistent posterior orientation in nullipara without mediolateral episiotomy as the clinical situation associated with the highest risk of severe perineal lacerations (12.5%). Conversely, patients with the lowest risk (0.1%) were those delivering spontaneously, neonates larger than 3200 g after mediolateral episiotomy.
Instrumental delivery, nulliparity, persistent posterior orientation and increased birth weight are independently associated with severe perineal lacerations. Restrictive use of mediolateral episiotomy protects against severe perineal lacerations especially in case of instrumental delivery.
No preview · Article · Aug 2014 · European Journal of Obstetrics & Gynecology and Reproductive Biology