Randomized Trial of Platelet-Transfusion Thresholds in Neonates.

BACKGROUND: Platelet transfusions are commonly used to prevent bleeding in preterm infants with thrombocytopenia. Data are lacking to provide guidance regarding thresholds for prophylactic platelet transfusions in preterm neonates with severe thrombocytopenia. METHODS: In this multicenter trial, we randomly assigned infants born at less than 34 weeks of gestation in whom severe thrombocytopenia developed to receive a platelet transfusion at platelet-count thresholds of 50,000 per cubic millimeter (high-threshold group) or 25,000 per cubic millimeter (low-threshold group). Bleeding was documented prospectively with the use of a validated bleeding-assessment tool. The primary outcome was death or new major bleeding within 28 days after randomization. RESULTS: A total of 660 infants (median birth weight, 740 g; and median gestational age, 26.6 weeks) underwent randomization. In the high-threshold group, 90% of the infants (296 of 328 infants) received at least one platelet transfusion, as compared with 53% (177 of 331 infants) in the low-threshold group. A new major bleeding episode or death occurred in 26% of the infants (85 of 324) in the high-threshold group and in 19% (61 of 329) in the low-threshold group (odds ratio, 1.57; 95% confidence interval [CI], 1.06 to 2.32; P=0.02). There was no significant difference between the groups with respect to rates of serious adverse events (25% in the high-threshold group and 22% in the low-threshold group; odds ratio, 1.14; 95% CI, 0.78 to 1.67). CONCLUSIONS: Among preterm infants with severe thrombocytopenia, those randomly assigned to receive platelet transfusions at a platelet-count threshold of 50,000 per cubic millimeter had a significantly higher rate of death or major bleeding within 28 days after randomization than those who received platelet transfusions at a platelet-count threshold of 25,000 per cubic millimeter. (Funded by the National Health Service Blood and Transplant Research and Development Committee and others; Current Controlled Trials number, ISRCTN87736839 .).

Assessing students' perceptions of the effects of a new Canadian longitudinal pre-clerkship family medicine experience.

BACKGROUND: Despite the implementation of longitudinal community-based pre-clerkship courses in several Canadian medical schools, there is a paucity of data assessing students' views regarding their experiences. The present study sought to measure students' perceived effects of the new Longitudinal Family Medicine Experience (LFME) course at McGill University. METHODS: A 34-item questionnaire called the 'LFME Survey (Student Version)' was created, and all first-year medical students completed it online. RESULTS: The participation rate was 64% (N = 120). Eight factors were identified in the factor analysis performed: overall satisfaction, satisfaction with preceptor, knowledge, affective learning, clinical skills, teaching/feedback, professional identity/professionalism and attitude toward primary care. Factor composite scores were above 4.5/7,indicating that students had positive perceptions of the LFME. Students felt that the LFME was a valuable educational experience and that their preceptors were good role-models. The course improved students' confidence, reinforced their commitment to being a physician and increased their positive attitude toward primary care. INTERPRETATION: Along with similar pre-clerkship courses, the LFME provides a valuable context for developing students' clinical skills, providing real-world cases, teaching patient-centred care and improving attitudes toward primary care. The LFME Survey appears to be a promising and innovative tool that deserves further validation.

Nurses' role in platelet transfusion clinical trials.

This article describes the crucial role of research nurses in studies coordinated by the NHS Blood and Transplant Clinical Trials Unit (CTU), using two recent trials studying platelet transfusions in adults and neonates as examples. CTU studies are coordinated by trial managers, most of whom are or were registered nurses, which supports relationships with research nurses in participating hospitals. During trials the CTU sustains research nurses with ongoing education and training, and establishes cooperative working between nurses and the unit, and between nurses in different locations. Regular feedback from research nurses guides the design and management of clinical trials.

Effects of early thyroid hormone deficiency on children's autobiographical memory performance.

Memory deficits and hippocampal abnormalities have been described in individuals with thyroid hormone (TH) insufficiencies; however, no study has yet examined their autobiographical memory (AM) abilities, which are known to be compromised by hippocampal damage. Investigations in adults have shown that AM consists of both episodic and semantic components and that the hippocampus is preferentially involved in episodic AM. The present study used the Children's Autobiographical Interview (CAI) to study episodic and semantic AM in 79 children aged 9 to 14 years, including 26 with early-treated congenital hypothyroidism (CH), 23 born to women with inadequately treated hypothyroidism during pregnancy (HYPO), and 30 typically developing controls. Results showed that relative to controls, CH and HYPO groups both exhibited weaknesses in episodic AM, but not semantic AM. In particular, CH and HYPO groups showed difficulty in recalling event details (i.e., the main happenings) and visual details from past experiences. Overall, this study highlights the importance of TH for early neurodevelopment and provides critical new insight into the effects of early treated TH deficiency on long-term memory performance. Furthermore, the present study indicates that the CAI is an effective tool for investigating episodic AM impairment in clinical pediatric populations.

Two-year outcomes following a randomised platelet transfusion trial in preterm infants.

OBJECTIVE: Assess mortality and neurodevelopmental outcomes at 2 years of corrected age in children who participated in the PlaNeT-2/MATISSE (Platelets for Neonatal Transfusion - 2/Management of Thrombocytopenia in Special Subgroup) study, which reported that a higher platelet transfusion threshold was associated with significantly increased mortality or major bleeding compared to a lower one. DESIGN: Randomised clinical trial, enrolling from June 2011 to August 2017. Follow-up was complete by January 2020. Caregivers were not blinded; however, outcome assessors were blinded to treatment group. SETTING: 43 level II/III/IV neonatal intensive care units (NICUs) across UK, Netherlands and Ireland. PATIENTS: 660 infants born at less than 34 weeks' gestation with platelet counts less than 50×109/L. INTERVENTIONS: Infants were randomised to undergo a platelet transfusion at platelet count thresholds of 50×109/L (higher threshold group) or 25×109/L (lower threshold group). MAIN OUTCOMES MEASURES: Our prespecified long-term follow-up outcome was a composite of death or neurodevelopmental impairment (developmental delay, cerebral palsy, seizure disorder, profound hearing or vision loss) at 2 years of corrected age. RESULTS: Follow-up data were available for 601 of 653 (92%) eligible participants. Of the 296 infants assigned to the higher threshold group, 147 (50%) died or survived with neurodevelopmental impairment, as compared with 120 (39%) of 305 infants assigned to the lower threshold group (OR 1.54, 95% CI 1.09 to 2.17, p=0.017). CONCLUSIONS: Infants randomised to a higher platelet transfusion threshold of 50×109/L compared with 25×109/L had a higher rate of death or significant neurodevelopmental impairment at a corrected age of 2 years. This further supports evidence of harm caused by high prophylactic platelet transfusion thresholds in preterm infants. TRIAL REGISTRATION NUMBER: ISRCTN87736839.

PHOENIX (Picking up Hidden Osteoporosis Effectively during Normal CT Imaging without additional X-rays): protocol for a randomised, multicentre feasibility study.

INTRODUCTION: Two million out of the UK's 5 million routine diagnostic CT scans performed each year incorporate the thoracolumbar spine or pelvic region. Up to one-third reveal undiagnosed osteoporosis or vertebral fractures. We developed an intervention, Picking up Hidden Osteoporosis Effectively during Normal CT Imaging without additional X-rays ('PHOENIX'), to facilitate early detection and management of osteoporosis in people attending hospitals for CT scans. METHODS AND ANALYSIS: A multicentre, randomised, pragmatic feasibility study. From the general CT-attending population, women aged ≥65 years and men aged ≥75 years attending for CT scans are invited to participate, via a novel consent form incorporating Fracture Risk Assessment (FRAX) questions. Those at increased 10-year risk (within the amber or red zones of the UK FRAX graphical outputs for further action) are block randomised (1:1:1) to (1) PHOENIX intervention, (2) active control or (3) usual care. The PHOENIX intervention comprises (i) retrieving the CT scans using the NHS Image Exchange Portal, (ii) Mindways QCT Pro software analysis of CT hip and spine none density with CT vertebral fracture assessment, (iii) sending the participants' general practitioner (GP) a clinical report including diagnosis, necessary investigations and recommended treatment. Baseline CT scans from groups 2 and 3 are assessed with the PHOENIX intervention only at study end. Assuming 25% attrition, the study is powered to find a predicted superior osteoporosis treatment rate with PHOENIX (20%) vs 16% among patients whose GPs were sent the FRAX questionnaire only (active control) and 5% in the usual care group. Five hospitals are participating to determine feasibility. The co-primary feasibility outcome measures are (a) ability to randomise 375 patients within 10 months and (b) retention of 75% of survivors, completing their 1-year bone health outcome questionnaire. Secondary 1-year outcomes include osteoporosis/vertebral fracture identification rates and osteoporosis treatment rates. Stakeholder acceptability and economic aspects are evaluated. ETHICS AND DISSEMINATION: Approved by committee (National Research Ethics Service) East of England (EE) as REF/19/EE/0176. Dissemination will be through the Royal Osteoporosis Society (to patients and public) as well as to clinician peers via national and international bone/rheumatology scientific and clinical meetings. TRIAL REGISTRATION NUMBER: ISRCTN14722819.

National survey of Canadian residents and program directors regarding parental leave during residency.

BACKGROUND: Despite the advantages of having a child as a medical resident, the transition back to residency after parental leave can be challenging. This study is the first to investigate this issue using a nation-wide Canadian sample of both residents and program directors. METHOD: A questionnaire was developed and made available online. Respondents included 437 female residents, 33 male residents, and 172 residency program directors. The mean length of parental leave was nine months for female residents and six weeks for male residents. Almost all female residents (97.5%) breastfed with an average duration of 12 months. The top challenges reported by residents were feeling guilty for being away from their family, long and unpredictable work hours, sleep deprivation, and finding time to study. When female residents and program directors were matched to both school and program (N = 99 pairs), there was no difference in the total number of challenges reported, but program directors reported offering significantly more accommodations than female residents reported being offered, t(196) = 13.06, p < .001. RESULTS: Our data indicate there is a need for better communication between resident parents and program directors, as well as clear program-specific parental leave policies, particularly for supporting breastfeeding mothers as they return to work.

CONTEXTE: Malgré les avantages d'avoir un enfant au cours d'une résidence en médecine, le retour à la résidence à la suite d'un congé parental peut s'avérer difficile. Cette recherche est la première qui étudie cette question en utilisant un échantillon national comptant à la fois des résidents et directeurs de programmes canadiens. MÉTHODE: Un questionnaire a été préparé et affiché en ligne. Parmi les personnes interrogées, on comptait 437 résidentes, 33 résidents et 172 directeurs et directrices de programmes de résidence. La durée moyenne des congés parentaux était de neuf mois pour les résidentes et six semaines pour les résidents. Presque toutes les résidentes (97,5%) ont allaité en moyenne pendant douze (12) mois. Les plus grands défis que les résidents ont signalés étaient la culpabilité de ne pas être avec leur famille, les longues et imprévisibles heures de travail, le manque de sommeil et la difficulté à trouver le temps pour étudier. Lorsque les résidentes et directeurs et directrices de programme étaient jumelés à l'école et au programme (N = 99 paires), le nombre total de difficultés rapportées est demeuré inchangé. Cependant, les directeurs et directrices de programme ont signalé qu'ils offraient beaucoup plus d'accommodements que ce que les résidentes ont déclaré qu'on leur proposait, t(196) = 13.06, p < .001. RÉSULTATS: Nos données indiquent qu'il est nécessaire d'améliorer la communication entre les résidents parents et les directeurs de programme ainsi que les politiques qui régissent les programmes de congés parentaux, notamment pour aider les mères qui allaitent au moment de retourner au travail.

Assessing Family Medicine Residents' Preparedness for the Practice of Geriatric Care.

INTRODUCTION: Family physicians provide care to a growing and often complex group of older adults. Family medicine residencies are expected to prepare trainees to manage the medical and social needs of these seniors, but whether they feel prepared to do so is unknown. This study aimed to assess family medicine residents' sense of preparedness to address geriatric-related issues, and to identify factors that might affect this self-evaluation. METHODS: As an exploratory cross-sectional study, a 28-item questionnaire was circulated among 180 McGill University family medicine residents for voluntary completion. The survey assessed residents' demographics, attitudes toward, and perceptions of their training in geriatrics. RESULTS: One hundred residents (55.5% response rate) completed the questionnaire. Residents perceived their level of preparedness increasing as they progressed in their training; however, they felt least comfortable managing behavioral problems and engaging community resources. Positive perceptions about their training for geriatric care was proportionate to the number of positive role models they had during training. Sense of preparedness was most strongly and significantly associated with the duration of exposure residents had to long-term care. CONCLUSION: The aging population requires physicians who are interested in care of the elderly and who are adequately prepared through comprehensive training to care for the complex medical and social issues that affect this large segment of society. This study, through its survey of family medicine residents, provides insights about potential curriculum changes and recommendations for updating the approach to care of the elderly.

Effects of prenatal alcohol exposure on hippocampal volume, verbal learning, and verbal and spatial recall in late childhood.

Children with prenatal alcohol exposure (PAE) show deficits in verbal learning and spatial memory, as well as abnormal hippocampal development. The relationship between their memory and neuroanatomic impairments, however, has not been directly explored. Given that the hippocampus is integral for the synthesis and retrieval of learned information and is particularly vulnerable to the teratogenic effects of alcohol, we assessed whether reduced learning and recall abilities in children with fetal alcohol spectrum disorders (FASDs) are associated with abnormal hippocampal volumes. Nineteen children with FASDs and 18 typically developing controls aged 9 to 15 years were assessed for verbal learning and verbal and spatial recall and underwent structural magnetic resonance imaging. Images were analyzed for total intracranial volume and for right and left hippocampal volumes. Results revealed smaller left hippocampi and poorer verbal learning and verbal and spatial recall performance in children with FASDs than controls, as well as positive correlations between selective memory indices and hippocampal volumes only in the FASD group. Additionally, hippocampal volumes increased significantly with age in controls only, suggesting that PAE may be associated with long-term abnormalities in hippocampal development that may contribute to impaired verbal learning and verbal and spatial recall.

Comparing Medical Students' and Preceptors' Views of a Longitudinal Preclerkship Family Medicine Course.

INTRODUCTION: Despite the increasing popularity of longitudinal primary care experiences in North America and beyond, there is a paucity of work assessing these medical undergraduate experiences using reliable and valid questionnaires. Our objective in this study was to evaluate a new preclerkship longitudinal family medicine experience (LFME) course at McGill University by assessing family physician preceptors' self-reported ratings of the perceived effects of this course, and to compare their responses with ratings provided by medical students who completed the course. METHODS: This study is part of a larger evaluative research project assessing the first edition of the LFME. Students (N=187) and preceptors (N=173) of the 2013-2014 cohort were invited to complete separate online questionnaires in the spring through summer of 2014. The preceptor survey contained 53 items, 14 of which were nearly identical to items in the student survey (published elsewhere) and served as the basis for comparing preceptor and student ratings of the LFME. RESULTS: Ninety-nine preceptors (57% response rate; 55% female) and 120 students (64% response rate; 58% female) completed the surveys. Preceptors and students did not significantly differ in their overall ratings of the course, as both groups were satisfied with the quality of the LFME and felt it was an appropriate and valuable educational experience. However, preceptors had more positive ratings regarding their role and the benefits of the course than did medical students. CONCLUSION: This study corroborates prior work showing extensive perceived benefits of longitudinal preclerkship exposure to primary care; however, preceptors were found to report more positive reviews of the course than students. This study also provides new innovative tools to assess students' and preceptors' perceptions of longitudinal, preclerkship family medicine courses available for use over time and in different educational contexts.

Activation of extracellular signal-regulated kinase by stretch-induced injury in astrocytes involves extracellular ATP and P2 purinergic receptors.

Gliosis is characterized by hypertrophic and hyperplastic responses of astrocytes to brain injury. To determine whether injury of astrocytes produced by an in vitro model of brain trauma activates extracellular signal-regulated protein kinase (ERK), a key regulator of cellular proliferation and differentiation, astrocytes cultured on deformable SILASTIC membranes were subjected to rapid, reversible strain (stretch)-induced injury. Activation of ERK was observed 1 min after injury, was maximal from 10 to 30 min, and remained elevated for 3 hr. Activation of ERK was dependent on the rate and magnitude of injury; maximum ERK activation was observed after a 20-60 msec, 7.5 mm membrane displacement. ERK activation was blocked by inhibiting MEK, the upstream activator of ERK. Activation of ERK was reduced when calcium influx was diminished. When extracellular ATP was hydrolyzed by apyrase or ATP/P2 receptors were blocked, injury-induced ERK activation was significantly reduced. P2 receptor antagonist studies indicated a role for P2X2 and P2Y1, but not P2X1, P2X3, or P2X7, receptors in injury-induced ERK activation. These findings demonstrate for the first time that ATP released by mechanical injury is one of the signals that triggers ERK activation and suggest a role for extracellular ATP, P2 purinergic receptors, and calcium-dependent ERK signaling in the astrocytic response to brain trauma.

Group I metabotropic receptor antagonism blocks depletion of calcium stores and reduces potentiated capacitative calcium entry in strain-injured neurons and astrocytes.

Antagonism of the group I metabotropic receptor subtype 1 (mGluR1) with (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA) has been shown to reduce deficits after in vivo or in vitro traumatic brain injury. We have previously demonstrated that AIDA prevents elevation of astrocyte IP3 subsequent to injury-induced activation of mGluRs and phospholipase C. Since IP3 can cause release of intracellular Ca2+ stores we tested the hypothesis that pre- or post-injury treatment with AIDA can affect (1) the depletion of Ca2+ stores which occurs soon after strain injury of cultured neurons and astrocytes and (2) the delayed potentiation of capacitative calcium entry in strain-injured neurons. Astrocyte or neuronal plus glial cultures were grown on Silastic membranes that were subjected to a 50-msec pulse of compressed gas, which caused membrane displacement and biaxial strain (stretch) injury of the adhering cells. Cells were treated 10 min before or immediately after injury with 100 microM AIDA and the intracellular free Ca2+ ([Ca2+]i) response to thapsigargin, which inhibits the ability of the stores to sequester Ca2+, was measured at 15 min or 3 h after injury. AIDA pre- or post-injury treatment prevented the depletion of intracellular calcium stores at 15 min post-injury in astrocytes and neurons and reduced the potentiated neuronal capacitative calcium influx 3 h after injury. Since Ca2+ and Ca2+ stores influence many factors, including neuronal excitability, plasticity, protein synthesis, and neuronal-glial interactions, prevention of Ca2+ store depletion and subsequent exaggerated capacitative calcium entry may be an important subcellular mechanism by which antagonism of mGluR1 receptors exert an injury-reducing effect. More globally, the results further emphasize the importance of altered signaling and calcium regulatory mechanisms in the immediate and delayed sequelae of traumatic brain injury.

Antagonism of group I metabotropic glutamate receptors and PLC attenuates increases in inositol trisphosphate and reduces reactive gliosis in strain-injured astrocytes.

We have previously found that in vitro traumatic injury uncouples IP3-mediated intracellular free calcium ([Ca2+]i) signaling in astrocytes (Rzigalinski et al., 1998; Floyd et al., 2001). Since Group I metabotropic glutamate receptors (mGluRs) are coupled to IP3-mediated Ca2+ signaling, we investigated their role in the in vitro strain injury of cultured astrocytes. Astrocytes grown on Silastic membranes were labeled with 3H-myo-inositol and strain (stretch)-injured. Cells injured in the presence of LiCl to prevent inositol phosphate metabolism were acid extracted and inositol phosphates (IPx) isolated using anion exchange columns. Reactive gliosis was assessed as increased glial fibrillary acidic protein immunoreactivity (GFAP-IR). Pre- but not post-injury administration of (RS)-1-aminoindan-15-decarboxylic acid (AIDA) or (S)-4-carboxy-3-hydroxyphenylglycine (S4CH3HPG), both group I mGluR antagonists, attenuated injury-induced increases in IPx. Injury increased GFAP-IR in astrocytes at 24 and 48 h post injury, which was reduced or blocked by AIDA or inhibition of phospholipase C (PLC) with U73122. These findings suggest that strain injury activates Group I mGluRs, causing aberrant IPx production and uncoupling of the PLC signaling pathway. Changes in this signaling pathway may be related to induction of reactive gliosis. Additionally, our results suggest a complex physical coupling between G protein receptor, PLC, and IP3 receptor, in support of the conformational coupling model.

NMDA receptor activation contributes to a portion of the decreased mitochondrial membrane potential and elevated intracellular free calcium in strain-injured neurons.

In our previous studies, we have shown that in vitro biaxial strain (stretch) injury of neurons in neuronal plus glial cultures increases intracellular free calcium ([Ca(2+)](i)) and decreases mitochondrial membrane potential (deltapsi(m)). The goal of this study was to determine whether strain injury, without the addition of exogenous agents, causes glutamate release, and whether NMDA receptor antagonists affect the post-strain injury rise in [Ca(2+)](i) and decrease in deltapsi(m). [Ca(2+)](i) and deltapsi(m) were measured using the fluorescent indicators fura-2 AM and rhodamine-1,2,3 (rh123). Strain injury of neuronal plus glial cultures caused an immediate 100-200 nM elevation in neuronal [Ca(2+)]i and a decline in neuronal deltapsi(m) by 15 min post-injury. Pretreatment with the NMDA receptor antagonist MK-801 (10 microM) attenuated the [Ca(2+)](i) elevation after mild, but not moderate and severe injury. MK-801 pretreatment reduced the decline in deltapsi(m) after mild and moderate, but not after severe injury. The NMDA receptor antagonist D-2-amino-5-phosphonopentanoic acid (APV; 100 microM) had effects similar to MK-801. Simultaneous measurement of [Ca(2+)](i) and deltapsi(m) demonstrated a significant correlation and a temporal relationship between [Ca(2+)](i) elevation and depression of deltapsi(m). We conclude that NMDA receptor stimulation contributes to some of the changes in [Ca(2+)](i) and deltapsi(m) after less severe strain injury. However, after more pronounced injury other mechanisms appear to be more involved.

Implicit learning modulates attention capture: evidence from an item-specific proportion congruency manipulation.

A host of research has now shown that our explicit goals and intentions can, in large part, overcome the capture of visual attention by objects that differ from their surroundings in terms of size, shape, or color. Surprisingly however, there is little evidence for the role of implicit learning in mitigating capture effects despite the fact that such learning has been shown to strongly affect behavior in a host of other performance domains. Here, we employ a modified attention capture paradigm, based on the work of Theeuwes (1991, 1992), in which participants must search for an odd-shaped target amongst homogeneous distracters. On each trial, there is also a salient, but irrelevant odd-colored distracter. Across the experiments reported, we intermix two search contexts: for one set of distracters (e.g., squares) the shape singleton and color singleton coincide on a majority of trials (high proportion congruent condition), whereas for the other set of distracters (e.g., circles) the shape and color singletons are highly unlikely to coincide (low proportion congruent condition). Crucially, we find that observers learn to allow the capture of attention by the salient distracter to a greater extent in the high, compared to the low proportion congruent condition, albeit only when search is sufficiently difficult. Moreover, this effect of prior experience on search behavior occurs in the absence of awareness of our proportion manipulation. We argue that low-level properties of the search displays recruit representations of prior experience in a rapid, flexible, and implicit manner.

Accuracy of episodic autobiographical memory in children with early thyroid hormone deficiency using a staged event.

Autobiographical memory (AM) is a highly constructive cognitive process that often contains memory errors. No study has specifically examined AM accuracy in children with abnormal development of the hippocampus, a crucial brain region for AM retrieval. Thus, the present study investigated AM accuracy in 68 typically and atypically developing children using a staged autobiographical event, the Children's Autobiographical Interview, and structural magnetic resonance imaging. The atypically developing group consisted of 17 children (HYPO) exposed during gestation to insufficient maternal thyroid hormone (TH), a critical substrate for hippocampal development, and 25 children with congenital hypothyroidism (CH), who were compared to 26 controls. Groups differed significantly in the number of accurate episodic details recalled and proportion accuracy scores, with controls having more accurate recollections of the staged event than both TH-deficient groups. Total hippocampal volumes and anterior hippocampal volumes were positively correlated with proportion accuracy scores, but not total accurate episodic details, in HYPO and CH. In addition, greater severity of TH deficiency predicted lower proportion accuracy scores in both HYPO and CH. Overall, these results indicate that children with early TH deficiency have deficits in AM accuracy and that the anterior hippocampus may play a particularly important role in accurate AM retrieval.

Effects of maternal hypothyroidism on offspring hippocampus and memory.

BACKGROUND: Rodents with gestational thyroid-hormone (TH) deficiencies and children with congenital hypothyroidism show abnormal hippocampal development. Given that the human hippocampus starts to develop early in gestation, we asked if children born to women with hypothyroidism during pregnancy also show hippocampal abnormalities and if this is related to the severity of maternal TH insufficiency and current memory functioning. We additionally sought to determine whether effects were more prominent in anterior or posterior hippocampal subsections given these support different memory functions and have different developmental trajectories. We hypothesized that these children would have smaller than normal hippocampal volumes than controls and show memory deficits on both standardized tests and indices of "everyday" memory functioning. METHODS: We studied 54 children aged 9 to 12 years: 30 controls and 24 HYPO cases-offspring from women diagnosed with hypothyroidism prior to or during pregnancy and treated with l-thyroxine. All children received a thorough assessment of memory functions and an MRI scan. For each child, right and left hippocampi were manually traced, and volumes of right and left hippocampi and anterior and posterior segments were determined. RESULTS: HYPO cases showed significantly smaller right and left hippocampal volumes than controls, particularly in right posterior and left anterior segments. In HYPO children, hippocampal volumes were negatively correlated with maternal third-trimester TSH levels and positively correlated with third-trimester fT4. HYPO cases scored significantly below controls on one objective and several subjective memory indices, and these were correlated with hippocampal volumes. CONCLUSION: Early TH insufficiency from maternal hypothyroidism affects offspring hippocampal development and memory.

Platelets for neonatal transfusion - study 2: a randomised controlled trial to compare two different platelet count thresholds for prophylactic platelet transfusion to preterm neonates.

INTRODUCTION: Neonatal thrombocytopenia is a common and important clinical problem in preterm neonates. A trial assessing clinically relevant outcomes in relation to the different platelet count thresholds used to trigger transfusion has never been undertaken in preterm neonates with severe thrombocytopenia. OBJECTIVES: Platelets for Neonatal Transfusion - Study 2 (PlaNeT-2) aims to assess whether a higher prophylactic platelet transfusion threshold is superior to the lower thresholds in current standard practice in reducing the proportion of patients who have a major bleed or die up to study day 28. METHODS: PlaNeT-2 is a two-stage, randomised, parallel-group, superiority trial. PlaNet-2 compares clinical outcomes in preterm neonates (<34 weeks' gestation at birth) randomised to receive prophylactic platelet transfusions to maintain platelet counts at or above either 25 × 10(9)/l or 50 × 10(9)/l. The primary outcome measure is the proportion of patients who either die or experience a major bleed up to and including study day 28. A total of 660 infants will be randomised. RESULTS AND CONCLUSIONS: This trial will help define optimal platelet transfusion support for severely thrombocytopenic preterm neonates by evaluating the risks and benefits of two different prophylactic neonatal platelet transfusion thresholds.

Neuroplastic effects of music lessons on hippocampal volume in children with congenital hypothyroidism.

Children with congenital hypothyroidism (CH) who experience a neonatal thyroid hormone deficiency have reduced hippocampal volumes compared with healthy controls. Interestingly, evidence suggests that musical training can contribute to structural plasticity in a number of brain areas, including the hippocampus. Therefore, we investigated whether taking music lessons could ameliorate the volumetric reductions of the hippocampus in children with CH. Left and right hippocampal volumes were measured in four groups of children: children with CH with and without music lessons, and healthy controls with and without music lessons. We found that the volume of the right hippocampus was comparable between children with CH who had taken music lessons and the healthy controls. Children with CH who had not taken music lessons had reduced hippocampal volumes compared with the other three groups. These results suggest that music lessons may induce structural neuroplasticity in children with atypical hippocampal development because of early thyroid hormone deficiencies.

Episodic and Semantic Autobiographical Memory and Everyday Memory during Late Childhood and Early Adolescence.

Few studies have examined both episodic and semantic autobiographical memory (AM) performance during late childhood and early adolescence. Using the newly developed Children's Autobiographical Interview (CAI), the present study examined the effects of age and sex on episodic and semantic AM and everyday memory in 182 children and adolescents. Results indicated that episodic and semantic AM both improved between 8 and 16 years of age; however, age-related changes were larger for episodic AM than for semantic AM. In addition, females were found to recall more episodic AM details, but not more semantic AM details, than males. Importantly, this sex difference in episodic AM recall was attenuated under conditions of high retrieval support (i.e., the use of probing questions). The ability to clearly visualize past events at the time of recollection was related to children's episodic AM recall performance, particularly the retrieval of perceptual details. Finally, similar age and sex effects were found between episodic AM and everyday memory ability (e.g., memory for everyday activities). More specifically, older participants and females exhibited better episodic AM and everyday memory performance than younger participants and males. Overall, the present study provides important new insight into both episodic and semantic AM performance, as well as the relation between episodic AM and everyday memory, during late childhood and adolescence.