Maternal perception of decreased fetal movements is independent of infant size.

OBJECTIVE: Fetal movements are often used as a surrogate for fetal wellbeing. Previous research suggests a link between maternal perception of decreased fetal movements (DFM) and small for gestational age (SGA) infants. The aim of this study was to investigate the association between maternal presentation with DFM and birthweight centile categories at a large Australian perinatal center. METHODS: This was a 5-year cohort study (January 2016 to October 2020) of non-anomalous singleton infants born at the Mater Mothers' Hospital in Brisbane, Australia at 28+0 weeks gestation or later. The primary outcome for this study was the rate of DFM by birthweight centile categories. Maternal demographics included age, body mass index, ethnicity, parity, medical conditions, and previous stillbirths. The effect of decreased fetal movements on birthweight centile was evaluated with adjusted multinomial regression models. Adjusted logistic regression models were then used to evaluate whether decreased fetal movements resulted in birthweight centiles <5 and <10. Robust standard errors were used to account for clustering at the patient level. Wald tests, Hosmer and Lemeshow's goodness of fit tests, Akaike's and Bayesian Information Criteria were used to evaluate models. RESULTS: Over the 5-year study period, 45042 women met the inclusion criteria. Of these, 6690 (14.9%) women presented with DFM. Of the DFM cohort, 80.9% (5411/6690) had only one presentation with DFM, whilst 19.1% (1279/6690) had >2 presentations. The overall stillbirth rate was similar in women with DFM (0.1%, 8/6690) and without DFM (0.1%, 50/38352). There was no difference in rates of DFM (either single or multiple) vs. no DFM and infant birthweight centile categories. There was no association between DFM (either single or multiple) and infant birth weight centile. CONCLUSION: The results of this study suggest that presentation with DFM is not associated with infant size. Clinicians should consider additional risk factors and the overall clinical context in deciding appropriate management. DFM is not necessarily an indication for an immediate or urgent ultrasound scan to assess fetal size. This article is protected by copyright. All rights reserved.

Accelerometer measures in extremely preterm and or extremely low birth weight infants and association with abnormal general movements assessments at 28- and 32-weeks postmenstrual age.

BACKGROUND: Assessment of general movements (GMs) in preterm infants is qualitative and potentially subjective. Accelerometers provide quantitative data that could overcome the problems of the GMs assessment. STUDY AIMS: To determine if quantitative measures (obtained from four tri-axial accelerometers) correlate with GMs assessments performed in the preterm period at 28- or 32-weeks postmenstrual age (PMA). STUDY DESIGN: Prospective observational study. Tri-axial accelerometers were applied to the dorsum of each hand and foot at 28- and 32-weeks PMA. Simultaneous video recordings of the babies' spontaneous movements were made to assess GMs. SUBJECTS: Eligible babies were born <28-weeks PMA or had a birth weight of <1000 g. Babies were recruited before they reached 33-weeks PMA. OUTCOME MEASURES: GMs assessments were made offline on the video recordings. Forty-six quantitative motor parameters were calculated during the same periods of activity and compared with GMs assessments. RESULTS: At 28-weeks PMA, 24/43 (55.8 %) babies had abnormal GMs. At 32-weeks PMA, 26/57 (45.6 %) had abnormal GMs. The inter-rater reliability of the GMs was poor. When comparing MDS measures between; infants with normal and those with abnormal GMs, at 28-weeks PMA, 7/46 parameters were significantly different, and at 32-weeks PMA, 19/46 parameters were significantly different. CONCLUSION: Isolated use of quantitative movement measures, obtained from four tri-axial accelerometers before hospital discharge, correlate with the GMs assessments at both 28-weeks and 32-weeks PMA. Accelerometers may provide a useful screening tool for abnormal GMs in preterm infants and could overcome issues with inter-rater reliability.

[How can the transition of adolescents from a children's to an adult CF center be improved? Analysis of adolescents' and parents' needs during the post-transfer period]. / Comment améliorer la transition au sein des CRCM : analyse des besoins des patients et de leurs parents lors de l'arrivée en service adulte.

INTRODUCTION: In 2018, 55.4% of the 7180 French cystic fibrosis (CF) patients were adults. Our study was aimed at identifying young adult patients' needs and those of their parents when the young adults arrived in an adult CF center. METHODOLOGY: Semi-structured interviews, conducted between July 2018 and December 2019and involving all the concerned teenagers and their parents, took place at least 6 months after their transfer. The interview guide dwelt on the aspects having had an impact on their experience of the transition. The interviews were recorded, transcribed and analyzed exhaustively. The results were classified by categorizing the contents according to respondent profile. RESULTS: Thirty-eight young adult patients and 16 parents were interviewed. As regards the young adults, analysis of their needs underlined the importance of their continuing to develop their skills in adaptation, communication and self-care. As regards their parents, they needed support in view of defining their role in their children's new care pathway. CONCLUSION: During and also following the transfer, therapeutic education for the parents as well as the young adults requires reinforcement.

Smoothing the transition of adolescents with CF from pediatric to adult care: Pre-transfer needs.

INTRODUCTION: In France, the cystic fibrosis (CF) care pathway is performed in 45 CF centers, the life expectancy of patients has steadily increased, but to date there are no national recommendations for the transition from pediatric to adult care. The transition to an adult CF center still raises questions about the relevance of its organizational arrangements. The "SAFETIM need" study aimed to identify the organizational needs both of patients and of parents before the transfer to an adult CF center. METHODS: This was a prospective, observational, multicenter study conducted between July 2017 and December 2018, involving the three CF centers of a regional network in southeastern France. Each adolescent registered with the center and his or her parents were interviewed individually, on the same day, during the 6 months leading up to transfer. They participated in semi-structured interviews during one of their routine consultations at the CF center. The interview manual, based on literature reviews and targeting national recommendations, was tested and validated by the national CF therapeutic education group (GETheM). All interviews were transcribed and checked by two different people, and analyzed by two researchers individually. The results were classified by topic according to content categorization. RESULTS: Overall, 43 adolescents and 41 parents were interviewed, respectively, who were followed up by CF centers: 14% (n=6) in a mixed CF center (pediatric and adult); 19% (n=8) and 67% (n=29), respectively, in two different pediatric CF centers. Adolescents were between 16 and 19 years old. For adolescents, the average interview time was 5.11min. (standard deviation [SD]: 3.8min; minimum: 2.53min; maximum: 17.14min). For parents, the average interview time was 7.99min (SD: 3.56min, minimum: 3.43min; maximum: 22.50min). DISCUSSION: Our study enquired only about the preparation and organization of the transfer. We identified three areas of actions matching the needs of adolescents and parents before transfer. The first one is to anticipate team change to prepare follow-up in their future CF center: acquire new skills, consider the future CF center according to the adolescent's curriculum, be involved in the transition process. The second area is to accompany the upcoming change. The care team could help by providing information and support during the start of teenagers' transition toward autonomy. And parents were aware that the CF center change will reverse roles. They must provide their own knowledge and manage the ambivalence of this as well as letting go. The third one is to announce the transition process and functioning of the future adult CF center, because the transition would require time to find their place (patients and parents) with the new team. CONCLUSION: The "SAFETIM needs" pre-transfer study results show that we can identify the main criteria to be developed and strengthened, to promote a smooth, high-quality transition from pediatric to adult CF care for patients in France. For most patients, the transition cannot be prepared at the last minute. Caregivers need to develop specific skills in adolescent and young adult care and follow-up. Each team must consider the transition as a normal part of the patient care cycle. While it must be structured, some flexibility must be allowed so as to give everyone the chance to be prepared and to personalize the care.

[Quality criteria for the transition to adult care in French CF centers - results from the SAFETIM APP study?] / Critères de qualité pour la transition dans la mucoviscidose en France (suivi des adolescents, des familles et des équipes, pour une transition idéale en mucoviscidose ­ analyse des pratiques professionnelles).

INTRODUCTION: SAFETIM-APP compiled an inventory of professional practice in the 45 French cystic fibrosis reference centres (CFRC), between February 2015 and December 2016, related to the transition of adolescents with cystic fibrosis to adult centres. METHOD: This multicentre cross-sectional study addressed the modalities of the transition in CFRCs and proposed a list of items that could be used to establish quality criteria. Quantitative analysis of the criteria and a qualitative analysis of the transition procedure were carried out. RESULTS: A total of 77% of the CFRCs that were contacted took part. Transition lasted 3 to 5 years and began at around 15 years of age. Nine criteria were described as fundamental, including: collaboration between teams, taking adolescence into account, having a time for adolescents to speak with the physician alone, defining a program including therapeutic education, involving the family, accompanying the parents. Seven additional criteria were noted to be important, including: re-announcing the diagnosis, identifying a common thread (caregiver) accompanying the family, scheduling adult follow-up from paediatrics onwards, visiting the adult department, organizing a formal departure/reception time, initiating the process early enough, identifying indicators to evaluate practices. CONCLUSION: The transition processes in place in CFRCs can be improved by implementing the use of these quality criteria systematically.

Molecular analysis and genotype-phenotype correlation of Diamond-Blackfan anemia.

Diamond-Blackfan anemia (DBA) features hypoplastic anemia and congenital malformations, largely caused by mutations in various ribosomal proteins. The aim of this study was to characterize the spectrum of genetic lesions causing DBA and identify genotypes that correlate with phenotypes of clinical significance. Seventy-four patients with DBA from across Canada were included. Nucleotide-level mutations or large deletions were identified in 10 ribosomal genes in 45 cases. The RPS19 mutation group was associated with higher requirement for chronic treatment for anemia than other DBA groups. Patients with RPS19 mutations, however, were more likely to maintain long-term corticosteroid response without requirement for further chronic transfusions. Conversely, patients with RPL11 mutations were less likely to need chronic treatment. Birth defects, including cardiac, skeletal, hand, cleft lip or palate and genitourinary malformations, also varied among the various genetic groups. Patients with RPS19 mutations had the fewest number of defects, while patients with RPL5 had the greatest number of birth defects. This is the first study to show differences between DBA genetic groups with regards to treatment. Previously unreported differences in the rate and types of birth defects were also identified. These data allow better patient counseling, a more personalized monitoring plan, and may also suggest differential functions of DBA genes on ribosome and extra-ribosomal functions.

Treatment decision-making among Canadian youth with severe haemophilia: a qualitative approach.

The first generation of young men using primary prophylaxis is coming of age. Important questions regarding the management of severe haemophilia with prophylaxis persist: Can prophylaxis be stopped? At what age? To what effect? Can the regimen be individualized? The reasons why some individuals discontinue or poorly comply with prophylaxis are not well understood. These issues have been explored using predominantly quantitative research approaches, yielding little insight into treatment decision-making from the perspectives of persons with haemophilia (PWH). Positioning the PWH as a source of expertise about their condition and its management, we undertook a qualitative study: (i) to explore and understand the lived experience of young men with severe haemophilia A or B and (ii) to identify the factors and inter-relationships between factors that affect young men's treatment decision-making. This manuscript reports primarily on the second objective. A modified Straussian, grounded theory methodology was used for data collection (interviews) and preliminary analysis. The study sample, youth aged 15-29, with severe haemophilia A or B, was chosen selectively and recruited through three Canadian Haemophilia Treatment Centres. We found treatment decision-making to be multi-factorial and used the Framework method to analyze the inter-relationships between factors. A typology of four distinct approaches to treatment was identified: lifestyle routine prophylaxis, situational prophylaxis, strict routine prophylaxis and no prophylaxis. Standardized treatment definitions (i.e.: 'primary' and 'secondary', 'prophylaxis') do not adequately describe the ways participants treat. Naming the variation of approaches documented in this study can improve PWH/provider communication, treatment planning and education.

Effect of flow rate, humidifier dome and water volume on maximising heated, humidified gas use for neonatal resuscitation.

AIM: Dry, cold gas is used for neonatal resuscitation, contributing to low admission temperatures and exacerbation of lung injury. Recently, a method of heating and humidifying neonatal resuscitation gases has become available. We aimed to determine the optimal flow rate, humidifier chamber and water volume needed to reach 36°C, and near 100% humidity at the patient T-piece in the shortest possible time. METHOD: A T-piece resuscitator was connected via a heated patient circuit to a humidifier chamber. Trials were performed using different gas flow rates (6, 8 and 10L/min), humidification chambers (MR290, MR225) and water volumes (30g, 108g). Temperature was recorded at the humidifier chamber (T1), distal temperature probe (T2) and the T-piece (T3) over a 20min period at 30s intervals. A test lung was added during one trial. RESULTS: No significant difference existed between flow rates 8L/min and 10L/min (p=0.091, p=0.631). T3 reached 36°C and remained stable at 360s (8L/min, MR225, 30mL); near 100% RH was reached at 107s (10L/min, MR225, 30mL). T3 and humidity reached and remained stable at 480s (10L/min, MR290, 30mL). Target temperature and humidity was not reached with the test lung. CONCLUSIONS: It is possible to deliver heated, humidified gases in neonatal resuscitation in a clinically acceptable timeframe. We suggest the set-up to achieve optimal temperature and humidity for resuscitation purposes is 10L/min of gas flow, a MR290 humidification chamber, and 30mL of water.

Methods of weaning preterm babies <30 weeks gestation off CPAP: a multicentre randomised controlled trial.

BACKGROUND: Controversy exists whether different continuous positive airway pressure (CPAP) weaning methods influence time to wean off CPAP, CPAP duration, oxygen duration, Bronchopulmonary Dysplasia (BPD) or length of admission. AIMS: In a multicentre randomised controlled trial, the authors have primarily compared CPAP weaning methods impact on time to wean off CPAP and CPAP duration and secondarily their effect on oxygen duration, BPD and time of admission. METHODS: Between April 2006 and October 2009, 177 infants <30 weeks gestational age (GA) who fulfilled stability criteria on CPAP were randomised to one of the three CPAP weaning methods (M). M1: Taken 'OFF' CPAP with the view to stay 'OFF'. M2: Cycled on and off CPAP with incremental time 'OFF'. M3: As with m(2), cycled on and off CPAP but during 'OFF' periods were supported by 2 mm nasal cannula at a flow of 0.5 l/min. RESULTS: Based on intention to treat analysis, there was no significant difference in mean GA or birthweight between the groups (27.1 ± 1.4, 26.9 ± 1.6 and 27.3 ± 1.5 (weeks ± 1SD) and 988 ± 247, 987 ± 249 and 1015 ± 257 (grams ± 1SD), respectively). Primary outcomes showed M1 produced a significantly shorter time to wean from CPAP (11.3 ± 0.8, 16.8 ± 1.0, 19.4 ± 1.3 (days ± 1SE) p<0.0001, respectively) and CPAP duration (24.4 ± 0.1, 38.6 ± 0.1, 30.5 ± 0.1 (days ± 1SE) p<0.0001, respectively). All the secondary outcomes were significantly shorter with M1, (oxygen duration: 24.1 ± 1.5, 45.8 ± 2.2, 34.1 ± 2.0 (days ± 1SE) p<0.0001, BPD: 7/56 (12.5%), 29/69 (42%), 10/52 (19%) p=0.011 and length of admission: 58.5 ± 0.1, 73.8 ± 0.1 69.5 ± 0.1 (days ± 1SE) p<0.0001, respectively). CONCLUSION: Method 1 significantly shortens CPAP weaning time, CPAP duration, oxygen duration, BPD and admission time.

Genetic analysis of inherited bone marrow failure syndromes from one prospective, comprehensive and population-based cohort and identification of novel mutations.

INTRODUCTION: Inherited bone marrow failure syndromes (IBMFSs) often have substantial phenotypic overlap, thus genotyping is often critical for establishing a diagnosis. OBJECTIVES AND METHODS: To determine the genetic characteristics and mutation profiles of IBMFSs, a comprehensive population-based study that prospectively enrols all typical and atypical cases without bias is required. The Canadian Inherited Marrow Failure Study is such a study, and was used to extract clinical and genetic information for patients enrolled up to May 2010. RESULTS: Among the 259 primary patients with IBMFS enrolled in the study, the most prevalent categories were Diamond-Blackfan anaemia (44 patients), Fanconi anaemia (39) and Shwachman-Diamond syndrome (35). The estimated incidence of the primary IBMFSs was 64.5 per 10(6) births, with Fanconi anaemia having the highest incidence (11.4 cases per 10(6) births). A large number of patients (70) had haematological and non-haematological features that did not fulfil the diagnostic criteria of any specific IBMFS category. Disease-causing mutations were identified in 53.5% of the 142 patients tested, and in 16 different genes. Ten novel mutations in SBDS, RPL5, FANCA, FANCG, MPL and G6PT were identified. The most common mutations were nonsense (31 alleles) and splice site (28). Genetic heterogeneity of most IBMFSs was evident; however, the most commonly mutated gene was SBDS, followed by FANCA and RPS19. CONCLUSION: From this the largest published comprehensive cohort of IBMFSs, it can be concluded that recent advances have led to successful genotyping of about half of the patients. Establishing a genetic diagnosis is still challenging and there is a critical need to develop novel diagnostic tools.

Comparative analysis of Shwachman-Diamond syndrome to other inherited bone marrow failure syndromes and genotype-phenotype correlation.

Our knowledge of the phenotypes of inherited bone marrow failure syndromes (IBMFSs) derives from case reports or case series in which only one IBMFS was studied. However, the substantial phenotypic overlap necessitates comparative analysis between the IBMFSs. Shwachman-Diamond syndrome (SDS) is an IBMFS that the appreciation of what comprises its clinical phenotype is still evolving. In this analysis we used data on 125 patients from the Canadian Inherited Marrow Failure Study (CIMFS), which is a prospective multicenter population-based study. Thirty-four cases of SDS patients were analyzed and compared to other patients with the four most common IBMFSs on the CIMFS: Diamond Blackfan anemia, Fanconi anemia (FA), Kostmann/severe congenital neutropenia and dyskeratosis congenita (DC). The diagnosis of SDS, FA and DC was often delayed relative to symptoms onset; indicating a major need for improving tools to establish a rapid diagnosis. We identified multiple phenotypic differences between SDS and other IBMFSs, including several novel differences. SBDS biallelic mutations were less frequent than in previous reports (81%). Importantly, compared to patients with biallelic mutations, patients with wild type SBDS had more severe hematological disease but milder pancreatic disease. In conclusion, comprehensive study of the IBMFSs can provide useful comparative data between the disorders. SBDS-negative SDS patients may have more severe hematological failure and milder pancreatic disease.

Prophylactic systemic antibiotics to reduce morbidity and mortality in neonates with central venous catheters.

BACKGROUND: The use of central venous catheters is recognised as a risk factor for nosocomial infection. Prophylactic antibiotics may be effective in preventing catheter-related blood stream infection in newborns but may also have the undesirable effect of promoting the emergence of resistant strains of micro-organisms. OBJECTIVES: To determine the effect of prophylactic antibiotics on mortality and morbidity in neonates with central venous catheters. SEARCH STRATEGY: Searches were done of the Cochrane Neonatal Review Group Specialised Register, MEDLINE from 1950 to April 2007, CINAHL from 1982 to April 2007, and the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2 2007). Previous reviews (including cross references) were also searched. SELECTION CRITERIA: Randomised controlled trials or quasi-randomised controlled trials of adequate quality in which either individual newborn infants or clusters of infants were randomised to receive prophylactic antibiotics (not including antifungals) versus placebo or no treatment. Infants must have had central venous catheters, been full term infants less than 28 days old or preterm infants up to 44 weeks (postmenstrual) corrected age. DATA COLLECTION AND ANALYSIS: Criteria and methods used to assess the methodological quality of the trials: standard methods of the Cochrane Collaboration and its Neonatal Review Group were used. The review authors extracted data independently. Attempts were made to contact study investigators for additional information as required. MAIN RESULTS: Three small studies have been included in this review. Prophylactic antibiotics in neonates with central venous catheters had no effect on overall mortality (typical RR 0.68, 95% confidence interval 0.31, 1.51). Prophylactic antibiotics in neonates with central venous catheters decreased the rate of proven bacterial sepsis (typical RR 0.38, 95% confidence interval 0.18, 0.82). Prophylactic antibiotics in neonates with central venous catheters decreased the rate of suspected or proven bacterial septicaemia (typical RR 0.40, 95% confidence interval 0.20, 0.78). No resistant organisms colonising infants were identified in any of the studies. No pooled data were available for other important outcome measures such as chronic lung disease or neurodevelopmental outcome. AUTHORS' CONCLUSIONS: Prophylactic systemic antibiotics in neonates with a central venous catheter reduces the rate of proven or suspected septicaemia. However, this may not be clinically important in the face of no significant difference in overall mortality and the lack of data on long-term neurodevelopmental outcome. Furthermore, there is a lack of data pertaining to the potentially significant disadvantages of this approach such as the selection of resistant organisms. The routine use of prophylactic antibiotics in infants with central venous catheters in neonatal units cannot currently be recommended.

Prophylactic antibiotics to reduce morbidity and mortality in neonates with umbilical artery catheters.

BACKGROUND: Umbilical artery catheters are often used in unwell neonates. Infection related to the use of these catheters may cause significant morbidity and mortality. The use of prophylactic antibiotics has been advocated for all newborns with umbilical artery catheters in order to reduce the risk of colonisation and acquired infection. Countering this is the possibility that harm, such as the emergence of antibiotic resistant organisms, may outweigh benefit. OBJECTIVES: The primary objective was to assess whether prophylactic antibiotics reduce mortality and morbidity in neonates with umbilical artery catheters. Two different policies regarding the prophylactic use of antibiotics in neonates with umbilical artery catheters were reviewed: 1) a policy of prophylactic antibiotics for the duration of catheterisation (or other fixed duration of antibiotic treatment) versus placebo or no treatment among neonates with umbilical artery catheters; 2) a policy of continuing versus discontinuing prophylactic antibiotics among neonates with umbilical artery catheters who had been started on antibiotics at the time of catheterisation but whose initial cultures to rule out sepsis are negative. SEARCH STRATEGY: MEDLINE (January 1950 to May 2007), CINAHL (1982 to May 2007), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2007), the Cochrane Neonatal Group Specialised Register and reference lists of articles were searched. SELECTION CRITERIA: Randomised and some non-randomised (i.e., quasi-randomised trials) controlled trials of adequate quality in which newborn infants with umbilical artery catheters are randomised to receive prophylactic antibiotics versus placebo or no treatment. DATA COLLECTION AND ANALYSIS: Two reviewer authors independently assessed trial quality. MAIN RESULTS: Two quasi-randomised trials have been included. However, given their poor quality, we have not pooled the results. There were no statistically significant differences in important outcomes in either study. AUTHORS' CONCLUSIONS: There is insufficient evidence from randomised trials to support or refute the use of prophylactic antibiotics when umbilical artery catheters are inserted in newborn infants, and no evidence to support or refute continuing antibiotics once initial cultures rule out infection in newborn infants with umbilical artery catheters.

Prophylactic antibiotics to reduce morbidity and mortality in ventilated newborn infants.

BACKGROUND: Intubation is associated with bacterial colonisation of the respiratory tract and, therefore, may increase the risk of acquiring an infection. The infection may prolong the need for mechanical ventilation and increase the risk of chronic lung disease. The use of prophylactic antibiotics has been advocated for all mechanically ventilated newborns in order to reduce the risk of colonisation and the acquisition of infection. However, there is the possibility that the harm this may cause might outweigh the benefit. OBJECTIVES: To assess the effects of prophylactic antibiotics on mortality and morbidity in intubated, ventilated newborn infants who are not known to have infection. In separate comparisons, two different policies regarding the prophylactic use of antibiotics in intubated, ventilated infants were reviewed: 1) among infants who have been intubated for mechanical ventilation, a policy of prophylactic antibiotics for the duration of intubation versus placebo or no treatment 2) among intubated, ventilated infants who have been started on antibiotics at the time of intubation but whose initial cultures to rule out sepsis were negative, a policy of continuing versus discontinuing prophylactic antibiotics. SEARCH STRATEGY: MEDLINE (January 1950 to March 2007), CINAHL (1982 to March 2007), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 1, 2007), the Cochrane Neonatal Group Specialised Register and reference lists of articles were searched. SELECTION CRITERIA: Randomised controlled trials of sufficient quality in which mechanically ventilated newborn infants are randomised to receive prophylactic antibiotics versus placebo or no treatment. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality. MAIN RESULTS: Two studies met the criteria for inclusion in this review. One was of insufficient quality to draw any meaningful conclusions. The other was of fair quality and found no significant differences between treatment and control groups in any of the reported outcomes, however, the rates of septicaemia were not reported. AUTHORS' CONCLUSIONS: There is insufficient evidence from randomised trials to support or refute the use of prophylactic antibiotics when starting mechanical ventilation in newborn infants, or to support or refute continuing antibiotics once initial cultures have ruled out infection in mechanically ventilated newborn infants.

Disease progression in recently diagnosed patients with inherited marrow failure syndromes: a Canadian Inherited Marrow Failure Registry (CIMFR) report.

BACKGROUND: Inherited bone marrow failure syndromes (IMFSs) are genetic disorders characterized by defective single-lineage or multi-lineage hematopoiesis. IMFS patients are at risk for severe cytopenias, development of marrow cytogenetic abnormalities (MCA), myelodysplasia (MDS), and malignancy. The rate of disease progression and proportion of patients at risk for these complications is currently unclear. We examined recently diagnosed IMFS patients to determine distribution of diagnoses, disease progression and development of significant outcomes. METHODS: The CIMFR is a prospective multi-center study established in 2001 to register all IMFS patients in Canada. Analysis was restricted to patients diagnosed after November 30, 1997. Summary statistics were used to depict the study population while survival was described using the Kaplan-Meier method. RESULTS: 74 CIMFR patients were considered recently diagnosed. Median age at diagnosis was 2.7 years (range, birth to 40.6). Annual follow-up data were available for 53 (72%) patients. The five most prevalent diagnoses were Fanconi anemia (FA), Shwachman-Diamond syndrome (SDS), Diamond-Blackfan anemia (DBA), dyskeratosis congenita (DKC), and Kostmann's neutropenia (KS). Eighteen (24%) patients were unclassifiable. Twenty-eight (53%) follow-up patients had disease progression as indicated by new or worsening cytopenias, new marrow changes, or initiation of transfusion support and/or medical therapy. Fourteen (19%) fulfilled minimal diagnostic criteria for myelodysplasia. Eleven patients had hematopoietic stem cell transplantation (HSCT) by first follow-up. Five patients have died. Survival at 36 months is 89.8 +/- 5.7%. CONCLUSIONS: IMFS patients are often diagnosed at a young age. The relative distribution of diagnoses is similar to previous reviews of published cases; however, 25% of patients are currently unclassifiable. Disease progression has occurred in approximately 50% of follow-up patients. Early mortality is noted. Continued prospective observation of these patients is warranted.

Achieving maximum ROI from corporate databases: exploiting your databases with integrated querying for better decision-making.

In order to increase the rate of drug discovery, pharmaceutical and biotechnology companies spend billions of dollars a year assembling research databases. Current trends still indicate a falling rate in the discovery of New Molecular Entities (NMEs). It is widely accepted that the data need to be integrated in order for it to add value. The degree to which this must be achieved is often misunderstood. The true goal of data integration must be to provide accessible knowledge. If knowledge cannot be gained from these data, then it will invalidate the business case for gathering it. Current data integration solutions focus on the initial task of integrating the actual data and to some extent, also address the need to allow users to access integrated information. Typically the search tools that are provided are either restrictive forms or free text based. While useful, neither of these solutions is suitable for providing full coverage of large numbers of integrated structured data sources. One solution to this accessibility problem is to present the integrated data in a collated manner that allows users to browse and explore it and also perform complex ad-hoc searches on it within a scientific context and without the need for advanced Information Technology (IT) skills. Additionally, the solution should be maintainable by 'in-house' administrators rather than requiring expensive consultancy. This paper examines the background to this problem, investigates the requirements for effective exploitation of corporate data and presents a novel effective solution.

Use of recombinant factor VIIa in pediatric patients with liver failure and severe coagulopathy.

BACKGROUND: Several reports have suggested a benefit for recombinant Factor VIIa (rFVIIa) in nonhematological conditions, including liver disease and transplantation. However, there are few reports of its use in children with liver failure. Recently, we used rFVIIa in four patients with liver failure and severe coagulopathy with bleeding who demonstrated significant laboratory and clinical improvement following its use with no side effects. PATIENTS AND METHODS: All four patients were hospitalized with liver failure, coagulopathy, and bleeding that was controlled with fresh frozen plasma, platelets, and other therapies, as indicated. Their international normalization ratios (INR) ranged from 1.7 to 5.8 (normal 0.9-1.1). All four patients received rFVIIa for bleeding episodes that were not responding to their usual therapy, for procedures with a high risk of bleeding, or both. The dose of rFVIIa ranged from 0.067 to 0.3 mg/kg. The INR improved to normal or near normal in all four patients. In all cases, bleeding stopped within 10 minutes of receiving the rFVIIa, and there were no complications observed. CONCLUSIONS: rFVIIa provided significant benefit in these children with liver failure and severe coagulopathy, in terms of clinical and laboratory improvement in their bleeding and coagulation profiles. There were no obvious side effects from the rFVIIa. This drug may be an important tool in the treatment of children with liver failure and more study is needed to define the optimal dosing for children.

Albumin infusion for low serum albumin in preterm newborn infants.

BACKGROUND: Intravenous albumin infusion to treat hypoalbuminaemia is used in intensive care nurseries. Hypoalbuminaemia occurs in a number of clinical situations including prematurity, the acutely unwell infant, respiratory distress syndrome (RDS), chronic lung disease (CLD), necrotising enterocolitis (NEC), intracranial haemorrhage, hydrops fetalis and oedema. Fluid overload is a potential side effect of albumin administration. Albumin is a blood product and therefore carries the potential risk of infection and adverse reactions. Albumin is also a scarce and expensive resource. OBJECTIVES: The primary objective was to assess whether albumin infusions, in preterm neonates with low serum albumin, reduces mortality and morbidity. A secondary objective was to assess whether albumin infusion is associated with significant side effects. SEARCH STRATEGY: Searches were made of MEDLINE from 1966 to April 2004, CINAHL from 1982 to April 2004 and the current Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library issue 1, 2004). Previous reviews (including cross references) and abstracts were also searched. SELECTION CRITERIA: All randomised controlled trials in which individual patients were allocated to albumin infusion versus control were included. Cross-over studies were excluded. Quasi randomised trials were excluded. Participants were preterm infants who had hypoalbuminaemia. Types of interventions included albumin infusion versus placebo (e.g. crystalloid) or no treatment. DATA COLLECTION AND ANALYSIS: The reviewers worked independently to search for trials for inclusion and to assess methodological quality. Studies were assessed using the following key criteria: blinding of randomisation, blinding of intervention, completeness of follow up and blinding of outcome measurement. MAIN RESULTS: Only two small studies were found for inclusion in this review and only one reported clinically relevant outcomes - it found no significant differences for our primary outcome measure of death (RR 1.5 [95% confidence interval 0.3 - 7.43]) or secondary outcome measures of intraventricular haemorrhage, patent ductus arteriosus, necrotising enterocolitis, bronchopulmonary dysplasia, duration of mechanical ventilation and duration of oxygen therapy. REVIEWERS' CONCLUSIONS: There is a lack of evidence from randomised trials to determine whether the routine use of albumin infusion, in preterm neonates with low serum albumin, reduces mortality or morbidity, and no evidence to assess whether albumin infusion is associated with significant side effects. There is a need for good quality, double-blind randomised controlled trials to assess the safety and efficacy of albumin infusions in preterm neonates with low serum albumin.