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.

A community-based child health and parenting intervention to improve child HIV testing, health, and development in rural Lesotho (Early Morning Star): a cluster-randomised, controlled trial.

BACKGROUND: When caregivers live in remote settings characterised by extreme poverty, poor access to health services, and high rates of HIV/AIDS, their caregiving ability and children's development might be compromised. We aimed to test the effectiveness of a community-based child health and parenting intervention to improve child HIV testing, health, and development in rural Lesotho. METHODS: We implemented a matched cluster-randomised, controlled trial in the Mokhotlong district in northeastern Lesotho with 34 community clusters randomly assigned to intervention or wait-list control groups within a pair. Eligible clusters were villages with non-governmental organisation partner presence and an active preschool. Participants were caregiver-child dyads, where the child was 12-60 months old at baseline. The intervention consisted of eight group sessions delivered at informal preschools to all children in each village. Mobile health events were hosted for all intervention (n=17) and control (n=17) clusters, offering HIV testing and other health services to all community members. Primary outcomes were caregiver-reported child HIV testing, child language development, and child attention. Assessments were done at baseline, immediately post-intervention (3 months post-baseline), and 12 months post-intervention. We assessed child language by means of one caregiver-report measure (MacArthur-Bates Communicative Development Inventory [CDI]) and used two observational assessments of receptive language (the Mullen Scales of Early Learning receptive language subscale, and the Peabody Picture Vocabulary Test 4th edn). Child attention was assessed by means of the Early Childhood Vigilance Task. Assessors were masked to group assignment. Analysis was by intention to treat. This trial was registered with ISRCTN.com, ISRCTN16654287 and is completed. FINDINGS: Between Aug 8, 2015, and Dec 10, 2017, 1040 children (531 intervention; 509 control) and their caregivers were enrolled in 34 clusters (17 intervention; 17 control). Compared with controls, the intervention group reported significantly higher child HIV testing at the 12-month follow-up (relative risk [RR] 1·46, 95% CI 1·29 to 1·65, p<0·0001), but not immediately post-intervention. The intervention group showed significantly higher child receptive language on the caregiver report (CDI) at immediate (effect size 3·79, 95% CI 0·78 to 6·79, p=0·028) but not at 12-month follow-up (effect size 2·96, 95% CI -0·10 to 5·98, p=0·056). There were no significant group differences for the direct assessments of receptive language. Child expressive language and child attention did not differ significantly between groups. INTERPRETATION: Integrated child health and parenting interventions, delivered by trained and supervised lay health workers, can improve both child HIV testing and child development. FUNDING: United States Agency for International Development (USAID) and the President's Emergency Plan for AIDS Relief (PEPFAR).

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.

Efficacy and moderators of short-term psychodynamic psychotherapy for depression: A systematic review and meta-analysis of individual participant data.

BACKGROUND: Short-term psychodynamic psychotherapy (STPP) is frequently used to treat depression, but it is unclear which patients might benefit specifically. Individual participant data (IPD) meta-analyses can provide more precise effect estimates than conventional meta-analyses and identify patient-level moderators. This IPD meta-analysis examined the efficacy and moderators of STPP for depression compared to control conditions. METHODS: PubMed, PsycInfo, Embase, and Cochrane Library were searched September 1st, 2022, to identify randomized trials comparing STPP to control conditions for adults with depression. IPD were requested and analyzed using mixed-effects models. RESULTS: IPD were obtained from 11 of the 13 (84.6%) studies identified (n = 771/837, 92.1%; mean age = 40.8, SD = 13.3; 79.3% female). STPP resulted in significantly lower depressive symptom levels than control conditions at post-treatment (d = -0.62, 95%CI [-0.76, -0.47], p < .001). At post-treatment, STPP was more efficacious for participants with longer rather than shorter current depressive episode durations. CONCLUSIONS: These results support the evidence base of STPP for depression and indicate episode duration as an effect modifier. This moderator finding, however, is observational and requires prospective validation in future large-scale trials.

Parental Scaffolding during Book-Sharing Predicts Child General Intelligence.

While much variance in general intelligence or g is genetic, a substantial environmental component suggests a possible role for parent-child interaction. In particular, previous evidence suggests the importance of parental scaffolding, or provision of cognitive structure to shape child behaviour. A role for scaffolding is consistent with the proposal that, in adult cognition, a critical aspect of g is decomposition of complex problems into a structure of simpler parts. Building on previous work, we recruited 162 parents attending Children's Centres with a child aged 2-4 years, and examined parental scaffolding during a book-sharing activity. Scaffolding was measured as the first principal component of a variety of parental behaviours, including sensitivity, focusing attention, extending comprehension, and promoting child participation. Child g was measured as the first principal component of a broad cognitive battery, including language, attention, working memory, and executive function. Importantly, we assessed contributions of the parent's own intelligence, education, and family income. Though these variables were all associated with both child g and parental scaffolding, scaffolding remained predictive of child g even once the influence of these variables was removed. In contrast to the correlation with cognitive proficiency, scaffolding did not predict child pro-social behaviour. We suggest that parental scaffolding supports the child's development of a broad skill of attentional structuring, promoting the across-the-board cognitive proficiency that is reflected in g.

Promoting wellbeing and empowerment via Youth First: Exploring psychosocial outcomes of a school-based resilience intervention in Bihar, India.

Youth worldwide are struggling with increased mental health concerns. As youth in low- and middle-income countries make up more than 20% of the world's population, finding ways to improve their psychosocial wellbeing is crucial. CorStone's Youth First program is a school-based psychosocial resilience program that seeks to improve the mental, physical, social, and educational wellbeing of early adolescents. The program is delivered via trained government schoolteachers who facilitate students' learning and development in small groups using a discussion and activity-based curriculum. In August 2021, a study among 322 adolescents was conducted to investigate and compare program participants' and non- participants' understanding and use of inter- and intra-personal psychosocial skills. Focus group discussions were held with students in eight intervention schools and four comparable schools not receiving the intervention (control). Through the focus group discussions, students provided their opinions, thoughts, and ideas about vignettes describing challenges that youth in their communities frequently face, including early marriage and financial pressures. Analysis integrated qualitative and quantitative approaches, consisting of an iterative thematic analysis process followed by quantizing data and conducting t-tests. Youth who had received Youth First had greater awareness of problems, perspective-taking, problem-solving strategies, helping approaches, awareness of their own strengths, and visions for the future, when compared with the control group. Findings provide insights into potential outcomes for measurement in future evaluations of mental health promotion and prevention programs among youth in low- and middle-income countries.

The effect of azithromycin on structural lung disease in infants with cystic fibrosis (COMBAT CF): a phase 3, randomised, double-blind, placebo-controlled clinical trial.

BACKGROUND: Structural lung disease and neutrophil-dominated airway inflammation is present from 3 months of age in children diagnosed with cystic fibrosis after newborn screening. We hypothesised that azithromycin, given three times weekly to infants with cystic fibrosis from diagnosis until age 36 months, would reduce the extent of structural lung disease as captured on chest CT scans. METHODS: A phase three, randomised, double-blind, placebo-controlled trial was done at eight paediatric cystic fibrosis centres in Australia and New Zealand. Infants (aged 3-6 months) diagnosed with cystic fibrosis following newborn screening were eligible. Exclusion criteria included prolonged mechanical ventilation in the first 3 months of life, clinically significant medical disease or comorbidities other than cystic fibrosis, or macrolide hypersensitivity. Participants were randomly assigned (1:1) to receive either azithromycin (10 mg/kg bodyweight orally three times per week) or matched placebo until age 36 months. Randomisation was done with a permuted block strategy and an interactive web-based response system, stratified by study site. Unblinding was done once all participants completed the trial. The two primary outcomes were the proportion of children with radiologically defined bronchiectasis, and the percentage of total lung volume affected by disease. Secondary outcomes included clinical outcomes and exploratory outcomes were inflammatory markers. Analyses were done with the intention-to-treat principle. This study is registered at ClinicalTrials.gov (NCT01270074). FINDINGS: Between June 15, 2012, and July 10, 2017, 281 patients were screened, of whom 130 were enrolled, randomly assigned, and received first study dose. 68 participants received azithromycin and 62 received placebo. At 36 months, 88% (n=50) of the azithromycin group and 94% (n=44) of the placebo group had bronchiectasis (odds ratio 0·49, 95% CI 0·12 to 2·00; p=0·32), and total airways disease did not differ between groups (median difference -0·02%, 95% CI -0·59 to 0·56; p=0·96). Secondary outcome results included fewer days in hospital for pulmonary exacerbations (mean difference -6·3, 95% CI -10·5 to -2·1; p=0·0037) and fewer courses of inhaled or oral antibiotics (incidence rate ratio 0·88, 95% CI 0·81 to 0·97; p=0·0088) for those in the azithromycin group. For the preplanned, exploratory analysis, concentrations of airway inflammation were lower for participants receiving azithromycin, including interleukin-8 (median difference -1·2 pg/mL, 95% CI -1·9 to -0·5; p=0·0012) and neutrophil elastase activity (-0·6 µg/mL, -1·1 to -0·2; p=0·0087) at age 36 months, although no difference was noted between the groups for interleukin-8 or neutrophil elastase activity at 12 months. There was no effect of azithromycin on body-mass index at age 36 months (mean difference 0·4, 95% CI -0·1 to 0·9; p=0·12), nor any evidence of pathogen emergence with the use of azithromycin. There were few adverse outcomes with no differences between the treatment groups. INTERPRETATION: Azithromycin treatment from diagnosis of cystic fibrosis did not reduce the extent of structural lung disease at 36 months of age; however, it did reduce airway inflammation, morbidity including pulmonary exacerbations in the first year of life and hospitalisations, and improved some clinical outcomes associated with cystic fibrosis lung disease. Therefore we suggest thrice-weekly azithromycin is a strategy that could be considered for the routine early management of paediatric patients with cystic fibrosis. FUNDING: Cystic Fibrosis Foundation.

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).

Factors in childhood associated with lung function decline to adolescence in cystic fibrosis.

BACKGROUND: Despite improvements in general health and life expectancy in people with cystic fibrosis (CF), lung function decline continues unabated during adolescence and early adult life. METHODS: We examined factors present at age 5-years that predicted lung function decline from childhood to adolescence in a longitudinal study of Australasian children with CF followed from 1999 to 2017. RESULTS: Lung function trajectories were calculated for 119 children with CF from childhood (median 5.0 [25%-75%=5.0-5.1]) years) to early adolescence (median 12.5 [25%-75%=11.4-13.8] years). Lung function fell progressively, with mean (standard deviation) annual change -0.105 (0.049) for forced vital capacity (FVC) Z-score (p<0.001), -0.135 (0.048) for forced expiratory volume in 1-second (FEV1) Z-score (p<0.001), -1.277 (0.221) for FEV1/FVC% (p<0.001), and -0.136 (0.052) for forced expiratory flow between 25% and 75% of FVC Z-score (p<0.001). Factors present in childhood predicting lung function decline to adolescence, in multivariable analyses, were hospitalisation for respiratory exacerbations in the first 5-years of life (FEV1/FVC p = 0.001, FEF25-75p = 0.01) and bronchoalveolar lavage neutrophil elastase activity (FEV1/FVC% p = 0.001, FEV1p = 0.05, FEF25-75p = 0.02). No examined factor predicted a decline in the FVC Z-score. CONCLUSIONS: Action in the first 5-years of life to prevent and/or treat respiratory exacerbations and counteract neutrophilic inflammation in the lower airways may reduce lung function decline in children with CF, and these should be targets of future research.

Dialogic Book-Sharing as a Privileged Intersubjective Space.

Parental reading to young children is well-established as being positively associated with child cognitive development, particularly their language development. Research indicates that a particular, "intersubjective," form of using books with children, "Dialogic Book-sharing" (DBS), is especially beneficial to infants and pre-school aged children, particularly when using picture books. The work on DBS to date has paid little attention to the theoretical and empirical underpinnings of the approach. Here, we address the question of what processes taking place during DBS confer benefits to child development, and why these processes are beneficial. In a novel integration of evidence, ranging from non-human primate communication through iconic gestures and pointing, archaeological data on Pre-hominid and early human art, to experimental and naturalistic studies of infant attention, cognitive processing, and language, we argue that DBS entails core characteristics that make it a privileged intersubjective space for the promotion of child cognitive and language development. This analysis, together with the findings of DBS intervention studies, provides a powerful intellectual basis for the wide-scale promotion of DBS, especially in disadvantaged populations.

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.

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.

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.

Impact of oral L-arginine supplementation on blood pressure dynamics in children with severe sickle cell vaso-occlusive crisis.

Sickle cell anaemia (SCA) patients generally have lower blood pressures compared to those with the AA haemoglobin genotype. However, during vaso-occlusive crises (SCA-VOC), blood pressures (BP) may elevate transiently to levels beyond the 95th percentile. The risk of stroke or even death increases with increasing systolic BP in SCA. Therefore, interventions targeted at BP reduction may be essential during severe vaso-occlusive episodes. Reduction in BP was achieved with arginine therapy in a meta-analysis of randomized controlled trials (RCT) in non-sickle cell adults. The impact of oral arginine (given for pain control) on the BP of children with SCA-VOC has not been documented. METHODS: A double-blind RCT of oral L-arginine hydrochloride as adjuvant therapy for pain reduction was conducted in children with SCA-VOC, aged 5-17 years, over a 2-year period. The mean change in BP and the time to achieve BP <90th percentile was added as part of the outcome variables. The anthropometry, pain scores and mercury sphygmomanometry were done following standard procedures. BP percentiles were generated using the Fourth Report guidelines. Differences in the time to normalization of BP in the treatment arms were tested with Kaplan-Meier analysis. RESULTS: Sixty-six children (57.6% male) were randomized into L-arginine (35 patients) or placebo (31 patients) arm. The prevalence of hypertension (BP ≥95th percentile) at presentation tended to increase as the pain scores increased, from a prevalence of 50% in patients with a score of 7 to 65% in those with score of 10 (systolic hypertension) and from 44.4% in patients with pain score of 7 to 50% in patients with pain score of 10 (diastolic hypertension). Patients that received arginine recorded a 12.8±3.2 mmHg decline in mean systolic BP compared to the placebo group, where a mean difference of 7.6±1.5 mmHg was observed, P<0.001. Similarly, the mean diastolic BP reduced by 13% in the arginine group and 7.5% in the placebo group, P<0.001. Children who received arginine tended to achieve BP normalization much faster than the placebo group (P=0.112), and no serious adverse events were documented related to the hypertension or arginine administration. CONCLUSIONS: High blood pressure (≥95th percentile) is common amongst children with SCA-VOC and are mostly asymptomatic. Administration of oral arginine given for pain control achieves a reduction of the BP at a faster rate in children compared to placebo and it is safe.

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.

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.

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.

Recommendations for clinical laboratory testing for protein C deficiency, for the subcommittee on plasma coagulation inhibitors of the ISTH.

Inherited protein C (PC) deficiency increases risk of venous thromboembolism (VTE) by 5 to 10-fold in thrombosis-prone families; however, heterozygous PC deficiency alone does not determine that a subject has thrombophilia. Protein C deficient subjects, who lack additional inherited risk factors such as factor V Leiden or have no major acquired risk factors, may not suffer from VTE. In addition, PC deficiency may be acquired, often due to vitamin K antagonist treatment or liver disease. In contrast, homozygous or compound heterozygous PC deficiencies are rare and serious disorders, and affected infants are often in families with no history of PC deficiency or thrombosis. Laboratories commonly use the chromogenic PC assay to diagnose deficiency. Chromogenic assay is recommended due to its good specificity, but this assay fails to detect the rare type 2b deficiency where the defect is due to poor interaction with calcium ions, phospholipid, protein S, and factor Va and factor VIIIa. The clotting-based assay of PC is capable of detecting type 2b deficiency but it has reduced specificity. Importantly, PC level varies with age, adult reference ranges cannot be applied to babies or children and levels may not reach those of adults even in adolescence. Pre-analytical variables in the specimen affect measurement of PC, and can be assay-dependent; for example, a partially clotted sample will have falsely raised PC level by chromogenic assay but reduced level by clotting-based assay. Direct oral anticoagulants falsely raise PC level in the clotting-based assay but the standard chromogenic assay is unaffected.

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.

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.