Patterns of sub-optimal change following CBT for childhood anxiety.

BACKGROUND: Children and adolescents demonstrate diverse patterns of symptom change and disorder remission following cognitive behavioural therapy (CBT) for anxiety disorders. To better understand children who respond sub-optimally to CBT, this study investigated youths (N = 1,483) who continued to meet criteria for one or more clinical anxiety diagnosis immediately following treatment or at any point during the 12 months following treatment. METHODS: Data were collected from 10 clinical sites with assessments at pre-and post-treatment and at least once more at 3, 6 or 12-month follow-up. Participants were assigned to one of three groups based on diagnostic status for youths who: (a) retained an anxiety diagnosis from post to end point (minimal responders); (b) remitted anxiety diagnoses at post but relapsed by end point (relapsed responders); and (c) retained a diagnosis at post but remitted to be diagnosis free at end point (delayed responders). Growth curve models assessed patterns of change over time for the three groups and examined predictors associated with these patterns including demographic, clinical and parental factors, as well as treatment factors. RESULTS: Higher primary disorder severity, being older, having a greater number of anxiety disorders, having social anxiety disorder, as well as higher maternal psychopathology differentiated the minimal responders from the delayed and relapsed responders at the baseline. Results from the growth curve models showed that severity of the primary disorder and treatment modality differentiated patterns of linear change only. Higher severity was associated with significantly less improvement over time for the minimal and relapsed response groups, as was receiving group CBT, when compared to the delayed response group. CONCLUSIONS: Sub-optimal response patterns can be partially differentiated using variables assessed at pre-treatment. Increased understanding of different patterns of change following treatment may provide direction for clinical decision-making and for tailoring treatments to specific groups of clinically anxious youth. Future research may benefit from assessing progress during treatment to detect emerging response patterns earlier.

Efficacy of a dialogic book-sharing intervention in a South African birth cohort: A randomized controlled trial.

OBJECTIVE: Evidence shows that dialogic book-sharing improves language development in young children in low-middle income countries (LMICs), particularly receptive and expressive language. It is unclear whether this intervention also boosts development of other neurocognitive and socio-emotional domains in children. Using a randomized controlled trial (RCT) nested in the Drakenstein Child Health Study (DCHS), a book-sharing intervention was implemented in caregivers of 3.5-year-old preschool children living in low-income South African communities. METHODS: 122 Caregivers and their children (mean age 3.5 years) were randomly assigned to an intervention group (n = 61) or waitlist control group (n = 61). A neurocognitive battery determined baseline receptive and expressive language, executive function, theory of mind, and behavior scores. RESULTS: No differences were observed between intervention and control groups on receptive and expressive language, or any of the neurocognitive or socio-emotional measures from baseline (3.5 years) to 4 months post-intervention administration (4 years). CONCLUSION: The benefits noted in prior literature of book-sharing in infants did not appear to be demonstrated at 4 months post-intervention, in children from 3.5 to 4 years of age. This suggests the importance of early intervention and emphasizes the need for further research on adaptation of book-sharing for older participants in a South African context. TRIAL REGISTRATION: retrospectively registered on 03/04/2022 PACTR202204697674974.

Effects of Two Early Parenting Programmes on Child Aggression and Risk for Violence in Brazil: a Randomised Controlled Trial.

Violence is a major public health problem globally, with the highest rates in low- and middle-income countries (LMICs) in the Americas and southern Africa. Parenting programmes in high-income countries can diminish risk for violence, by reducing risk factors such as child aggression and harsh parenting, and increasing protective factors such as child cognitive development and school readiness. However, there is critical need to identify low-cost programmes with replicable benefits that work in real-world LMICs contexts. A three-arm, randomised, single-blind trial evaluated effects of two low-cost, group-based parenting programmes recommended for LMICs (ACT: Raising Safe Kids; DBS: dialogic book-sharing) on child aggression (primary outcome), child development, parenting, maltreatment, and stress. Participants were 369 children with medium-high levels of aggression (mean age 3.1 years at baseline) in poor households. Interventions were implemented in city health and education services in southern Brazil. Maternal reports, filmed observations, child tasks, and hair cortisol were assessed at baseline, 1-month post-intervention, and 8-month follow-up. Intention-to-treat analyses compared each of ACT and DBS with a control group. Three hundred sixty-eight (99.7%) participants completed follow-up assessments 8 months after the interventions. There was no effect of ACT (standardised mean difference, SMD 0.11, 95% CI - 0.05, 0.27) or DBS (SMD 0.05, 95% CI - 0.11, 0.21) on the primary outcome of child aggression. ACT reduced harsh parenting behaviour post-intervention (SMD - 0.23; 95% CI - 0.46, - 0.01), but not at follow-up. DBS improved book-sharing practices at both time points (e.g., maternal sensitivity at follow-up SMD 0.33; 95% CI 0.08, 0.57). There were no benefits of either programme for other parenting, child development, or stress outcomes. Two parenting programmes in Brazil had small effects on parenting practices but did not reduce child aggression or several other important risk/protective factors for violence. Effective early interventions that reduce violence in real-world LMIC settings are highly desirable but may be challenging to achieve.

Saline at lower tonicity in cystic fibrosis (SALTI-CF) trial comparing 0.9% versus 3% versus 6% nebulised saline.

BACKGROUND: In people with cystic fibrosis (CF), regular nebulisation of 6% or 7% saline improves lung function; however, these concentrations are not always tolerable. Clinically, some CF patients report using lower concentrations of saline to improve tolerability, yet the effects of lower concentrations are unknown. This study therefore aimed to evaluate the relative effectiveness and tolerability of 0.9% versus 3% versus 6% saline nebulised twice daily with an eFlow rapid nebuliser. METHODS: This was a randomised, blinded, placebo-controlled, parallel-group, multicentre study where subjects inhaled 4 mL of 0.9%, 3% or 6% saline twice daily for 16 weeks. The primary outcome was forced expiratory volume in 1 s. The secondary outcomes were: forced vital capacity (FVC) and forced expiratory flow at 25-75% of FVC; quality of life; exercise capacity; acquisition or loss of bacterial organisms in expectorated sputum; tolerability of nebulised saline; pulmonary exacerbations; and adverse events. RESULTS: 140 participants were randomised to 0.9% (n=47), 3% (n=48) or 6% (n=45) saline. 134 participants (96%) contributed to the intention-to-treat analysis. 3% saline significantly improved lung function and increased the time to first pulmonary exacerbation compared with 0.9% saline but did not improve quality of life. 6% saline had similar benefits to 3% saline but also significantly improved quality of life compared with 3% saline. Only 6% saline delayed the time to intravenous antibiotics for pulmonary exacerbation. Tolerability and adherence were similar. CONCLUSIONS: Dilution of 6% saline to 3% maintains the benefits for lung function and exacerbation prevention; however, the positive impacts of 6% saline on quality of life and time to i.v. antibiotics for pulmonary exacerbations are lost.

Arginine Therapy and Cardiopulmonary Hemodynamics in Hospitalized Children with Sickle Cell Anemia: A Prospective, Double-blinded, Randomized Placebo-controlled Clinical Trial.

Rationale: Acute changes in cardiopulmonary hemodynamics that include tricuspid regurgitant jet velocity (TRV) elevation measured by Doppler echocardiography are often encountered during sickle cell vasoocclusive pain and acute chest syndrome (ACS). Arginine and nitric oxide depletion develop in patients with these complications. Arginine administration may therefore improve nitric oxide bioavailability and potentiate pulmonary vasodilatation. Objectives: To evaluate effects of l-arginine supplementation on Doppler indices of cardiopulmonary hemodynamics in children with sickle cell anemia experiencing pain. Methods: This was a prospective, double-blinded, randomized placebo-controlled trial of oral arginine in children with sickle cell anemia age 5-17 years hospitalized with severe pain and/or ACS. Measurements and Main Results: Blood biomarkers and Doppler echocardiographic indices of cardiopulmonary hemodynamics were measured before and after supplementation. The mean change in TRV, pulmonary artery systolic pressure, mean pulmonary artery pressure, and other indices of cardiopulmonary hemodynamics were tested with paired Student's t test and correlated with markers of arginine bioavailability using Pearson correlation. Sixty-six children were randomized into arginine versus placebo groups. An elevated TRV ⩾ 2.5 m/s was seen in 40 (61%) patients. A Day 5 Doppler echocardiogram was performed in 47 patients who remained hospitalized. A greater reduction in median TRV occurred in the arginine group than placebo (22.2%, n = 22 vs. 3.8%, n = 25; p < 0.01). A larger percentage increase in global arginine bioavailability was associated with a lower TRV after 5 days of supplementation (r = -0.533; P = 0.001). Significant differences in multiple indices of cardiopulmonary hemodynamics and mean N-terminal pro B-type brain natriuretic peptide were also noted after arginine therapy. Conclusions: Oral arginine supplementation improves cardiopulmonary hemodynamics during sickle cell disease vasoocclusive pain and ACS.Clinical trial registered with Pan African Clinical Trial Registry https://pactr.samrc.ac.za/Search.aspx (PACTR201611001864290).

First 1,000 days: enough for mothers but not for children? Long-term outcomes of an early intervention on maternal depressed mood and child cognitive development: follow-up of a randomised controlled trial.

BACKGROUND: Child cognitive development is often compromised in contexts of poverty and adversity, and these deficits tend to endure and affect the child across the life course. In the conditions of poverty and violence that characterise many low- and middle-income countries (LMIC), the capacity of parents to provide the kind of care that promotes good child development may be severely compromised, especially where caregivers suffer from depression. One avenue of early intervention focuses on the quality of the early mother-infant relationship. The aim of this study was to examine the long-term impact of an early intervention to improve the mother-infant relationship quality on child cognitive outcomes at 13 years of age. We also estimated the current costs to replicate the intervention. METHOD: We re-recruited 333 children from an early childhood maternal-infant attachment intervention, 'Thula Sana', when the children were 13 years old, to assess whether there were impacts of the intervention on child cognitive outcomes, and maternal mood. We used the Kaufman Assessment Battery to assess the child cognitive development and the Patient Health Questionnaire (PHQ-9) and the Self-Reporting Questionnaire (SRQ-20) to assess maternal mental health. RESULTS: Effect estimates indicated a pattern of null findings for the impact of the intervention on child cognitive development. However, the intervention had an effect on caregiver psychological distress (PHQ-9, ES = -0.17 [CI: -1.95, 0.05] and SRQ-20, ES = -0.30 [CI: -2.41, -0.19]), but not anxiety. The annual cost per mother-child pair to replicate the Thula Sana intervention in 2019 was estimated at ZAR13,365 ($780). CONCLUSION: In a socio-economically deprived peri-urban settlement in South Africa, a home visiting intervention, delivered by community workers to mothers in pregnancy and the first six postpartum months, had no overall effect on child cognitive development at 13 years of age. However, those caregivers who were part of the original intervention showed lasting improvements in depressed mood. Despite the fact that there was no intervention effect on long-term child outcomes, the improvements in maternal mood are important.

Randomized control trial of oral arginine therapy for children with sickle cell anemia hospitalized for pain in Nigeria.

Low arginine bioavailability is associated with vaso-occlusive painful crisis (VOC) severity in sickle cell anemia (SCA) and predicts need for pediatric hospitalization. Intravenous arginine therapy has opioid-sparing effects and was found to significantly decrease pain scores in children hospitalized with SCA-VOC in a phase-two randomized placebo-controlled trial (RCT). Efficacy of oral arginine is unknown. Our objective was to determine the safety and efficacy of oral arginine therapy in Nigerian children with SCA. A double-blind RCT of oral L-arginine-hydrochloride (100 mg/kg TID) was conducted in children with SCA-VOC, aged 5-17 years, hospitalized at two Nigerian sites. The primary outcome measure was analgesic usage, quantified by difference in the mean Analgesic Medication Quantification Scale (MQS). Secondary outcomes included daily pain scores, time-to-crisis-resolution and length-of-hospital-stay. An intention-to-treat analysis was performed. Sixty-eight children (age 5-17 years, mean 10.6 ± 0.4 years; 56% male), were randomized to receive L-arginine (35 patients) or placebo (33 patients). The mean total MQS for the arginine group was 73.4 (95% CI, 62.4-84.3) vs 120.0 (96.7-143.3) for placebo (P < .001). The mean rate of decline in worst pain scores was faster in the arginine arm vs placebo (1.50 [1.23-1.77] vs 1.09 [0.94-1.24] point/d, P = .009). Children receiving arginine had a shorter time-to-crisis-resolution (P = .02), shorter hospital-stay (P = .002) and experienced no serious adverse event. Pain control was more rapid, total analgesic requirement was significantly reduced, and most notably, time-to-crisis-resolution and length-of-hospital-stay were shorter in children with SCA-VOC receiving arginine vs placebo. Given the established safety and low cost, oral arginine is a promising adjuvant therapy for SCA-VOC management.

Book-Sharing for Parenting and Child Development in South Africa: A Randomized Controlled Trial.

This study evaluated the impact of a parenting intervention on children's cognitive and socioemotional development in a group of caregivers and their 21-to-28-month-old children in a low-income South African township. A randomized controlled trial compared an experimental group (n = 70) receiving training in dialogic book-sharing (8 weekly group sessions) with a wait-list control group (n = 70). They were assessed before the intervention, immediately following it, and at a six month follow-up. The intervention had positive effects on child language and attention, but not behavior problems, prosocial behavior, or theory of mind. Intervention caregivers were less verbally and psychologically harsh, showed more sensitivity and reciprocity and more complex cognitive talk. This program benefitted parenting and child development and holds promise for low-income contexts.

Review of Radiofrequency Ablation for Peripheral Nerves.

PURPOSE OF REVIEW: Radiofrequency ablation (RFA) has become an increasingly widespread treatment tool for various chronic pain syndromes within the last two decades with the majority of publications on the topic coming after 2006. Not only are clinicians using RFA to treat more peripheral nerve pain syndromes but the technology itself is evolving quickly to the point that it is nearly impossible to stay abreast on the complexity of such a diversely utilized instrument. This review summarizes studies that focus on the use of RFA for peripheral nerve neurotomy and anatomical studies regarding RFA published between 2015 and 2020. RECENT FINDINGS: Topics in this review include anatomical regions or nerves of the body published since 2015. Significant findings are summarized in each section. Peripheral nerve RFA is rapidly changing. Many studies have been performed over the last 5 years showing the usefulness of RFA.

The impact of a mother-infant intervention on parenting and infant response to challenge: A pilot randomized controlled trial with adolescent mothers in El Salvador.

A pilot randomized controlled trial (RCT) was conducted in El Salvador of an intervention ('Thula Sana') previously shown to enhance maternal sensitivity and infant security of attachment in a South African sample. In El Salvador, trained community workers delivered the intervention from late pregnancy to 6 months postpartum as part of a home-visiting programme. The sample comprised 64 pregnant adolescent women, aged 14-19 years, living in predominantly rural settings. They were randomised to receive either the intervention or normal care. Demographic information was collected at baseline and, immediately post-intervention, blind assessments were made of parental sensitivity and infant emotion regulation. The intervention was found to have a substantial positive impact on maternal sensitivity. Further, compared to control group, infants in the intervention group showed more regulated behaviour: in a social challenge task they showed more attempts to restore communication, and in a non-social challenge task they showed more social and goal-directed behaviour. This replication and extension of the South African findings in a small El Salvador sample shows promise and justifies the conduct of a large-scale RCT in a Central or South American context.

Un ensayo piloto controlado al azar se llevó a cabo en El Salvador sobre una intervención ('Thula Sana') que previamente había mostrado en un grupo muestra sudafricano el mejoramiento de la sensibilidad materna y la seguridad de la afectividad del infante. En El Salvador, trabajadores entrenados de la comunidad llevaron la intervención como parte de un programa de visitas a casa a partir de la última etapa del embarazo hasta seis meses después del parto. El grupo muestra estuvo compuesto por 64 mujeres adolescentes embarazadas, de entre 14 y 19 años, que vivían en áreas predominantemente rurales. Ellas fueron asignadas al azar para recibir o la intervención o el cuidado normal. Al inicio, se recogió la información demográfica e, inmediatamente después de la intervención, se llevaron a cabo evaluaciones ciegas sobre la sensibilidad de la progenitora y la regulación de la emoción del infante. Se determinó que la intervención tenía un impacto positivo considerable sobre la sensibilidad materna. Es más, comparados con el grupo de control, los infantes en el grupo de intervención mostraron una conducta más regulada: en una tarea de reto social mostraron más intentos de restaurar la comunicación, y en una tarea que no era de reto social, mostraron una conducta más sociable y enfocada en el objetivo. La reproducción y extensión de los resultados sudafricanos en un pequeño grupo muestra en el Salvador es prometedora y justifica que se lleve a cabo un ensayo controlado al azar (RCT) a mayor escala dentro de un contexto centro o suramericano.

The Impact of a Mother-Infant Intervention on Parenting and Infant Response to Challenge: a pilot randomized controlled trial with Adolescent Mothers in El Salvador Un essai randomisé contrôlé pilote a été fait au Salvador, d'une intervention ('Thuna Sana') dont on avait précédemment démontré dans un échantillon Sud-Africain qu'elle améliore la sensibilité maternelle et la sécurité de l'attachement du nourrisson. Au Salvador des agents communautaires formés ont fourni l'intervention de la fin de la grossesse à six mois postpartum, comme faisant partie d'un programme de visite à domicile. L'échantillon a consisté en 64 adolescentes enceintes, âgées de 14 à 19 ans, vivant principalement en milieux ruraux. Elles ont été randomisées afin de recevoir soit l'intention soit les soins normaux. Les renseignements démographiques ont été recueillis au début de l'étude et, immédiatement après l'intervention des évaluations aveugles ont été faites de la sensibilité parentale et de la régulation de l'émotion du bébé. Nous avons trouvé que l'intervention s'est avérée avoir un impact positif important sur la sensibilité maternelle. De plus, comparés au groupe contrôle, les nourrissons du groupe d'intervention ont fait preuve de plus de comportement régulé: lors d'une tâche de défi sociale ils ont fait preuve de plus de tentatives pour restaurer la communication et durant une tâche de défi non-social ils ont fait preuve d'un comportement plus social et plus orienté vers un but. Cette réplique et extension des résultats Sud-Africains dans un petit échantillon du Salvador est prometteur et justifier un essai randomisé contrôlé à large échelle dans un contexte Sud-Américain et en Amérique Centrale.

Early markers of cystic fibrosis structural lung disease: follow-up of the ACFBAL cohort.

Little is known about early predictors of later cystic fibrosis (CF) structural lung disease. This study examined early predictors of progressive structural lung abnormalities in children who completed the Australasian CF Bronchoalveolar Lavage (ACFBAL) clinical trial at age 5-years and participated in an observational follow-up study (CF-FAB).Eight Australian and New Zealand CF centres participated in CF-FAB and provided follow-up chest computed-tomography (CT) scans for children who had completed the ACFBAL study with baseline scans at age 5-years. CT scans were annotated using PRAGMA-CF scoring. Ordinal regression analysis and linear regression were used to investigate associations between PRAGMA-CF (Perth-Rotterdam Annotated Grid Morphometric Analysis for CF) outcomes at follow-up and variables measured during the ACFBAL study.99 out of 157 ACFBAL children (mean±sd age 13±1.5 years) participated in the CF-FAB study. The probability of bronchiectasis at follow-up increased with airway disease severity on the baseline CT scan. In multiple regression (retaining factors at p<0.05) the extent of bronchiectasis at follow-up was associated with baseline atelectasis (OR 7.2, 95% CI 2.4-22; p≤ 0.001), bronchoalveolar lavage (BAL) log2 interleukin (IL)-8 (OR 1.2, 95% CI 1.05-1.5; p=0.010) and body mass index z-score (OR 0.49, 95% CI 0.24-1.00; p=0.05) at age 5 years. Percentage trapped air at follow-up was associated with BAL log2 IL-8 (coefficient 1.3, 95% CI 0.57-2.1; p<0.001) at age 5 years.The extent of airway disease, atelectasis, airway inflammation and poor nutritional status in early childhood are risk factors for progressive structural lung disease in adolescence.

The role of maternal anxiety disorder subtype, parenting and infant stable temperamental inhibition in child anxiety: a prospective longitudinal study.

BACKGROUND: Social anxiety disorder (SAD) aggregates in families. To elucidate intergenerational transmission of risk, we examined whether childhood SAD and symptoms of anxiety were prospectively predicted by stable infant temperamental inhibition, maternal SAD, maternal generalized anxiety disorder (GAD) and maternal parenting behaviours. METHODS: We conducted a longitudinal study beginning prenatally with follow-up at 4, 10, 14 and 58 months postnatally. Mothers were assessed for anxiety disorders prenatally and assigned to one of three groups: SAD (n = 67), GAD (n = 56) and nonanxious controls (n = 94). We assessed infant temperamental inhibition at 4 and 14 months, maternal parenting behaviours at 10 and 58 months, and child anxiety disorders and symptoms at 58 months. RESULTS: Child SAD at 58 months was predicted by prenatal maternal SAD (OR = 23.76, 95% CI = 1.15-60.37), but not by prenatal maternal GAD (OR = 7.44, 95% CI = 0.32-124.49), stable temperamental inhibition or maternal behaviours. Child anxiety symptoms at 58 months were predicted specifically by maternal SAD (but not GAD), and also by concurrent maternal intrusiveness. Stable temperamental inhibition moderated the association between 10-month maternal encouragement and 58-month child anxiety symptoms. CONCLUSIONS: We found evidence for specificity of risk for child SAD and anxiety symptoms from maternal SAD compared to maternal GAD. Childhood anxiety symptoms were also predicted by an interaction between a lack of maternal encouragement in infancy and stable temperamental inhibition, as well as concurrent maternal intrusiveness. The findings have clinical implications for targeted prevention of child anxiety.

A randomised controlled trial of treatments of childhood anxiety disorder in the context of maternal anxiety disorder: clinical and cost-effectiveness outcomes.

BACKGROUND: This study evaluated whether clinical and economic outcomes from CBT for child anxiety disorders in the context of maternal anxiety disorders are improved by adding treatment focused on (a) maternal anxiety disorders or (b) mother-child interactions. METHODS: Two hundred and eleven children (7-12 years, 85% White British, 52% female) with a primary anxiety disorder, whose mothers also had a current anxiety disorder, were randomised to receive (a) child-focused CBT with nonspecific control interventions (CCBT+Con), (b) CCBT with CBT for the maternal anxiety disorder (CCBT+MCBT), or (c) CCBT with an intervention targeting the mother-child interaction (CCBT+MCI). A cost-utility analysis from a societal perspective was conducted using mother/child combined quality-adjusted life years (QALYs). [Trial registration: https://doi.org/10.1186/isrctn19762288]. RESULTS: MCBT was associated with immediate reductions in maternal anxiety compared to the nonspecific control; however, after children had also received CCBT, maternal outcomes in the CCBT+MCI and CCBT+Con arms improved and CCBT+MCBT was no longer superior. Neither CCBT+MCBT nor CCBT+MCI conferred a benefit over CCBT+Con in terms of child anxiety disorder diagnoses post-treatment [primary outcome] (adj RR: 1.22 (95% CI: 0.88, 1.67), p = .23; adj RR: 1.21 (95% CI: 0.88, 1.65), p = .24, respectively) or global improvement ratings (adj RR: 1.25 (95% CI: 0.99, 1.57), p = .06; adj RR: 1.18 (95% CI: 0.93, 1.50), p = .17) or six and 12 months later. No significant differences between the groups were found on the main economic outcome measures (child/mother combined QALY mean difference: CCBT+MCBT vs. CCBT+Con: -0.04 (95% CI: -0.12, 0.04), p = .29; CCBT+MCI vs. CCBT+Con: 0.02 (95% CI: -0.05, -0.09), p = .54). CCBT+MCI was associated with nonsignificantly higher costs than CCBT (mean difference: £154 (95% CI: -£1,239, £1,547), p = .83) but, when taking into account sampling uncertainty, it may be cost-effective compared with CCBT alone. CONCLUSIONS: Good outcomes were achieved for children and their mothers across treatment arms. There was no evidence of significant clinical benefit from supplementing CCBT with either CBT for the maternal anxiety disorder or treatment focussed on mother-child interactions, but the addition of MCI (and not MCBT) may be cost-effective.

Shared Picture Book Reading Interventions for Child Language Development: A Systematic Review and Meta-Analysis.

Interventions that train parents to share picture books with children are seen as a strategy for supporting child language development. We conducted meta-analyses using robust variance estimation modeling on results from 19 RCTs (Ntotal  = 2,594; Mchildage  = 1-6 years). Overall, book-sharing interventions had a small sized effect on both expressive language (d = 0.41) and receptive language (d = 0.26). They had a large effect on caregiver book-sharing competence (d = 1.01). The impact of the intervention on child language was moderated by intervention dosage, with lower dosage associated with a minimal impact. Child age and caregiver education level were unrelated to child outcome. This review and meta-analysis confirms the promise of book-sharing interventions for enhancing and accelerating child language development.

Cardiovascular changes in children with sickle cell crisis.

BACKGROUND: Sickle cell anaemia is characterised by frequent, sometimes serious events referred to as "crisis". Cardiopulmonary consequences such as pulmonary hypertension and myocardial ischaemia may accompany a serious crisis. OBJECTIVE: To determine the cardiovascular changes that occur during a severe sickle cell crisis. METHODS: A cross-sectional comparative study of sickle cell anaemia in children (5-17 years) admitted during a severe crisis (cases) and those in steady state (controls) was conducted over a 2-year period. Effects of the crisis on the cardiopulmonary system were assessed. The diagnosis of myocardial ischaemia was made using electrocardiography and serological cardiac biomarkers, while cardiac dysfunction and the presence of pulmonary hypertension were determined using echocardiography. The presence of systemic hypertension and tachycardia was also evaluated. RESULTS: A total of 176 patients were recruited, 92 in steady state (male:female ratio, 1.2:1) and 84 in severe crisis (male:female ratio, 1.3:1). The mean age was 10.4 ± 3.2 years for steady state and 10.5 ± 3.4 years for those in crisis. The mean heart rate in crisis was higher than in steady state (p < 0.0001). The blood pressures (systolic, p < 0.0001, diastolic, p < 0.0001, mean, p < 0.0001) as well as myocardial ischaemia scores (p < 0.0001) were higher in patients with crisis than in those in steady state. Similarly, conduction abnormalities, pulmonary hypertension, and ventricular dysfunction were more prevalent in the crisis than in the steady state. CONCLUSION: The present data suggest that sickle cell crisis results in a derangement of clinical, electrocardiographical, and echocardiographical parameters in children with sickle cell anaemia. Further research on these cardiovascular events may improve the overall care of these patients.

Associations between family factors, childhood adversity, negative life events and child anxiety disorders: an exploratory study of diagnostic specificity.

BACKGROUND: Chronic childhood adversity, negative life events, and anxiogenic parenting behaviours have all been implicated in the development and maintenance of childhood anxiety disorders. However, few studies have addressed whether these factors are associated with particular types of childhood anxiety disorders. AIMS: The aims of this study were to investigate whether specific associations were obtained between specific types of childhood anxiety disorder - namely, social anxiety disorder (SOC), separation anxiety disorder (SEP) and generalized anxiety disorder (GAD) - and the nature of particular forms of psycho-social risk - namely, chronic childhood adversity, negative life events, and particular forms of parenting behaviours. METHOD: Two-hundred and ten children (aged 7-12 years) who met diagnostic criteria for SOC, SEP or GAD and their primary caregivers completed questionnaire measures on chronic childhood adversity and negative life events. In addition, dyads participated in two laboratory-based assessments of parent-child interactions. RESULTS: We found little evidence for disorder specificity for chronic childhood adversity and negative life events, except in the case of separation anxiety disorder. Anxious children with separation anxiety were more likely than children with other forms of anxiety disorders to live with a single parent, experience more frequent parent arguments, and more negative life events. No group differences in observed parenting behaviours were found. CONCLUSIONS: Childhood SEP may be particularly associated with family challenges which may need specific consideration to optimize prevention and/or treatment. Beyond this, there is limited evidence of specific associations between family and environmental factors and specific types of childhood anxiety disorders.

Improving mother-infant interaction during infant feeding: A randomised controlled trial in a low-income community in South Africa.

BACKGROUND: Maternal-infant feeding interactions are a primary context for engagement between mothers and their infants, and constitute a unique space in which reciprocity, attunement and maternal sensitivity can be expressed. Increasingly, research demonstrates the importance of the psychological and social nature of the feeding context, and how it may be affected by maternal mental state, feeding skills and sensitivity. As such, feeding interactions may provide useful contexts for observations of maternal sensitivity, reflecting well on day-to-day maternal sensitivity. AIMS AND OBJECTIVES: This paper is a post hoc examination of the impact of an intervention on maternal sensitivity during a feeding interaction when the infants were 6 months old. PARTICIPANTS: A total of 449 women consented to participate in the original intervention and were randomly assigned to the intervention or control groups. Mothers and infants were assessed during pregnancy, and then at 2, 6, 12 and 18 months of infant age. At the 6 month follow-up visit, 79% (354 out of 449) of the participants were retained. Post hoc analyses were conducted on the original sample to determine breastfeeding status. Sixty-nine percent of the women completed the feeding observation at the 6 months follow-up visit, of which 47% reported exclusively breastfeeding and 22% reported bottle-feeding. RESULTS: Results demonstrated that during a feeding interaction, maternal sensitivity was significantly improved among non-breastfeeding mothers who received the intervention. Particularly, maternal responsiveness to infant cues and synchronous interactions was higher among non-breastfeeding intervention mothers compared to control group mothers. The results also show that non-breastfeeding mothers who received the intervention were significantly less intrusive in their interactions with their infants. CONCLUSION: The intervention had particular beneficial effects for mothers who were not breastfeeding and suggest that the intervention offered a protective effect for non-breastfeeding mothers.

Trasfondo: Las interacciones materno-infantiles de alimentación son un contexto primario de compromiso interactivo entre madres y sus infantes. Alimentar al infante es un proceso complejo que requiere no sólo que se provean los nutrientes, sino también una relación social entre el cuidador y el infante. Metas y Objetivos: Este artículo es un examen a posteriori del impacto de una intervención sobre la sensibilidad materna durante una interacción de alimentación cuando los infantes tenían seis meses de edad. Participantes: Un total de 449 mujeres consintieron en participar en la intervención original y fueron asignadas al azar a la propia intervención o a los grupos de control. A la visita de seguimiento de los seis meses, el 79% (354 de las 449) de las participantes aún se mantenían. Se llevaron a cabo análisis a posteriori en el grupo muestra original para determinar la condición de amamantamiento. Resultados: Durante una interacción de alimentación, la sensibilidad materna mejoró significativamente entre las madres que no amamantaban y que recibieron la intervención. La sensibilidad materna a las señales del infante y a las interacciones sincrónicas fue más alta entre madres de la intervención que no amamantaban tal como se les comparó con las madres del grupo de control. Conclusión: Estos resultados demuestran particularmente los efectos beneficiosos para las madres en el grupo de intervención que no estaban amamantando, y sugieren que la intervención ofreció un efecto de protección para las madres que no amamantaban.

Contexte: Les interactions maternelles-bébé durant l'alimentation sont un contexte primaire pour l'engagement entre les mères et leurs bébés. Nourrir son bébé est un processus complexe qui inclut non seulement le transfert d'éléments nutritifs mais également une relation sociale entre la personne prenant soin du bébé et le bébé. Buts et Objectifs: Cet article est une étude post hoc de l'impact d'une intervention sur la sensibilité maternelle durant une interaction d'alimentation lorsque les bébés avaient six mois. Participantes: Un total de 449 femmes ont consenti à participer à l'intervention originelle et ont été réparties au hasard au groupe d'intervention ou au groupe de contrôle. A la visite de suivi de six mois 79% (354 sur 449) des participantes ont été retenues. Les analyses post hoc analyses ont été faites sur l'échantillon d'origine afin de déterminer le statut d'allaitement au sein. Résultats: Durant une interaction d'alimentation, la sensibilité maternelle a été améliorée de manière importante chez les mères de donnant pas le sein qui recevaient l'intervention. La réaction maternelle aux signes du bébé et les interactions synchronisées étaient plus élevées chez les mères du groupe d'intervention de non allaitement au sein comparées au groupe de mères de contrôle. Conclusion: Ces résultats dénotent des effets particulièrement favorables pour les mères du groupe d'intervention qui n'allaitaient pas au sein, et suggèrent que l'intervention a offert un effet protecteur pour les mères n'allaitant pas leurs bébé au sein.

Long-term efficacy and safety results of taliglucerase alfa through 5years in adult treatment-naïve patients with Gaucher disease.

Taliglucerase alfa, the first available plant cell-expressed recombinant therapeutic protein, is an enzyme replacement therapy approved for Gaucher disease (GD). PB-06-001, a pivotal phase 3, multicenter, randomized, double-blind, parallel-dose study investigated taliglucerase alfa 30 or 60U/kg every other week through 9months in treatment-naïve adults with GD; 30-month extension study PB-06-003 followed. Patients completing PB-06-001 and PB-06-003 could continue treatment in PB-06-007. Nineteen patients enrolled in PB-06-007 (30U/kg, n=8; 60U/kg, n=9; dose adjusted, n=2); 17 completed 5 total years of treatment. In these 3 groups, respectively, taliglucerase alfa resulted in mean decreases in spleen volume (-8.7, -6.9, -12.4 multiples of normal), liver volume (-0.6, -0.4, -0.5 multiples of normal), chitotriosidase activity (-83.1%, -93.4%, -87.9%), and chemokine (CC motif) ligand 18 concentration (-66.7%, -83.3%, -78.9%), as well as mean increases in hemoglobin concentration (+2.1, +2.1, +1.8mg/dL) and platelet count (+31,871, +106,800, +34,000/mm3). The most common adverse events were nasopharyngitis and arthralgia. Most adverse events were mild/moderate; no serious adverse events were considered treatment-related. These results demonstrate continued improvement of disease parameters during 5years of taliglucerase alfa therapy in 17 treatment-naive patients with no new safety concerns, extending the taliglucerase alfa clinical efficacy and safety dataset. This study was registered at www.clinicaltrials.gov as NCT01422187.

A review of -multidrug-resistant Enterobacteriaceae in a neonatal unit in Johannesburg, South Africa.

BACKGROUND: Multi-drug resistant organisms are an increasingly important cause of neonatal sepsis. AIM: This study aimed to review neonatal sepsis caused by multi-drug resistant Enterobacteriaceae (MDRE) in neonates in Johannesburg, South Africa. METHODS: This was a cross sectional retrospective review of MDRE in neonates admitted to a tertiary neonatal unit between 1 January 2013 and 31 December 2015. RESULTS: There were 465 infections in 291 neonates. 68.6% were very low birth weight (< 1500 g). The median age of infection was 14.0 days. Risk factors for MDRE included prematurity (p = 0.01), lower birth weight (p = 0.04), maternal HIV infection (p = 0.02) and oxygen on day 28 (p < 0.001). The most common isolate was Klebsiella pneumoniae (66.2%). Total MDRE isolates increased from 0.39 per 1000 neonatal admissions in 2013 to 1.4 per 1000 neonatal admissions in 2015 (p < 0.001). There was an increase in carbapenem-resistant Enterobacteriaceae (CRE) from 2.6% in 2013 to 8.9% in 2015 (p = 0.06). Most of the CRE were New Delhi metallo-ß lactamase- (NDM) producers. The all-cause mortality rate was 33.3%. Birth weight (p = 0.003), necrotising enterocolitis (p < 0.001) and mechanical ventilation (p = 0.007) were significantly associated with mortality. Serratia marcescens was isolated in 55.2% of neonates that died. CONCLUSIONS: There was a significant increase in MDRE in neonatal sepsis during the study period, with the emergence of CRE. This confirms the urgent need to intensify antimicrobial stewardship efforts and address infection control and prevention in neonatal units in LMICs. Overuse of broad- spectrum antibiotics should be prevented.

Long-term safety and efficacy of taliglucerase alfa in pediatric Gaucher disease patients who were treatment-naïve or previously treated with imiglucerase.

Taliglucerase alfa is an enzyme replacement therapy approved for treatment of Gaucher disease (GD) in children and adults in several countries. This multicenter extension study assessed the efficacy and safety of taliglucerase alfa in pediatric patients with GD who were treatment-naïve (n=10) or switched from imiglucerase (n=5). Patients received taliglucerase alfa 30 or 60U/kg (treatment-naïve) or the same dose as previously treated with imiglucerase every other week. In treatment-naïve patients, taliglucerase alfa 30 and 60U/kg, respectively, reduced mean spleen volume (-18.6 multiples of normal [MN] and -26.0MN), liver volume (-0.8MN and -0.9MN), and chitotriosidase activity (-72.7% and -84.4%), and increased mean Hb concentration (+2.0g/dL and +2.3g/dL) and mean platelet count (+38,200/mm3 and +138,250/mm3) from baseline through 36 total months of treatment. In patients previously treated with imiglucerase, these disease parameters remained stable through 33 total months of treatment with taliglucerase alfa. Most adverse events were mild/moderate; treatment was well tolerated. These findings extend the taliglucerase alfa safety and efficacy profile and demonstrate long-term clinical improvement in treatment-naïve children receiving taliglucerase alfa and maintenance of disease stability in children switched to taliglucerase alfa. Treatment was well-tolerated, with no new safety signals. This study is registered at www.clinicaltrials.gov as NCT01411228.