BackgroundChildren in low- and middle-income countries face obstacles to optimal language and cognitive development due to a variety of factors related to adverse socioeconomic conditions. One of these factors is compromised caregiver-child interactions and associated pressures on parenting. Early development interventions, such as dialogic book-sharing (DBS), address this variable, with evidence from both high-income countries and urban areas of low- and middle-income countries showing that such interventions enhance caregiver-child interaction and the associated benefits for child cognitive and socioemotional development. Yet, evidence for DBS effects is lacking from poor rural communities where the need for such early development intervention may be greatest. ObjectiveThe objective of this study is to assess the effects of a DBS intervention, a parenting program for female caregivers of children aged between 15 and 45 months, implemented in rural Tanzania. We aim to assess the impact of the intervention on the following domains: child cognitive and socioemotional skills, parenting and parental stress, and child health. MethodsThe study is a 3-arm cluster randomized controlled trial. In total, 443 female caregivers participated in the study. Clusters of caregivers were randomized to either (1) an index DBS intervention group, (2) a playful activity active control group, or (3) a waitlist control group. The active control group was designed to control for any attention effects, ensuring that observed improvement in the index group can be attributed to the DBS intervention’s content. The primary outcomes were child language, parental sensitivity, and parent-child interaction. The secondary outcomes concerned child attention and behavior, parenting practices, and parental stress. A combination of questionnaires and direct observations was applied. Qualitative methods were also used, primarily to capture caregivers’ experiences and subjective perspectives on intervention-induced changes. ResultsData collection for the study was completed in September 2024. The study results are expected to be published by late 2025. ConclusionsThis randomized controlled trial of a DBS intervention implemented in rural Tanzania adds to a growing body of international literature exploring the impact and limitations of a simple and scalable early development intervention to enhance child outcomes. Trial RegistrationInternational Standard Registered Clinical/Social Study Number (ISRCTN) ISRCTN12613329; https://www.isrctn.com/ISRCTN12613329 International Registered Report Identifier (IRRID)DERR1-10.2196/68758

BACKGROUND:Cystic fibrosis (CF) lung disease begins early in life and progresses throughout childhood into adolescence. Children completing the Australasian CF Bronchoalveolar Lavage (ACFBAL) trial were followed longitudinally (CF-FAB study) to determine progression of CF lung disease during adolescence using visual and automatic methods and to correlate CT-derived metrics with spirometry outcomes. METHODS:CTs from start and end visits of CF-FAB (mean 24 [SD 12] months apart) were analysed using visual PRAGMA-CF scoring and automatic bronchus-artery (BA) analysis. PRAGMA-CF assessed %Disease by summing %Bronchiectasis, %Mucus plugging, % Airway wall thickening on inspiratory scans and %Trapped air on expiratory scans. The BA-analysis segments the bronchial tree, identifies segmental bronchi (G0) and distal generations (G1, G2, G3…), measures diameters of bronchial outer wall (Bout), inner wall (Bin), wall thickness (Bwt), and artery (A), and computes BA-ratios (Bout/A, Bin/A, Bwt/A, Bwa/Boa[=bronchial wall area/bronchial outer area]) to evaluate bronchial dilatation and wall thickening. RESULTS:120 children (median age 13 years, IQR 11.4-14) contributed 115 start and 105 end scans. Eleven children were treated with CFTR modulators prior to the start of the study and four received the treatment during the study. Progression was found in PRAGMA-CF %Bronchiectasis (p=0.02) and %Mucus plugging (p=0.02), and Bout/A (p=0.01), Bwt/A (p<0.001), and Bwa/Boa (p<0.001). Spirometry outcomes showed no significant decline. BA-metrics correlated more strongly with spirometry outcomes than PRAGMA-CF scores. CONCLUSION:Heterogeneous progression of structural lung disease in children with CF during adolescence was detected using visual PRAGMA-CF scores and automatic BA-analysis. Spirometry outcomes showed no significant decline.

Background: The identification of predictors of treatment response is crucial for improving treatment outcome for children with anxiety disorders. Machine learning methods provide opportunities to identify combinations of factors that contribute to risk prediction models. Methods: A machine learning approach was applied to predict anxiety disorder remission in a large sample of 2114 anxious youth (5-18 years). Potential predictors included demographic, clinical, parental, and treatment variables with data obtained pre-treatment, post-treatment, and at least one follow-up. Results: All machine learning models performed similarly for remission outcomes, with AUC between 0.67 and 0.69. There was significant alignment between the factors that contributed to the models predicting two target outcomes: remission of all anxiety disorders and the primary anxiety disorder. Children who were older, had multiple anxiety disorders, comorbid depression, comorbid externalising disorders, received group treatment and therapy delivered by a more experienced therapist, and who had a parent with higher anxiety and depression symptoms, were more likely than other children to still meet criteria for anxiety disorders at the completion of therapy. In both models, the absence of a social anxiety disorder and being treated by a therapist with less experience contributed to the model predicting a higher likelihood of remission. Conclusions: These findings underscore the utility of prediction models that may indicate which children are more likely to remit or are more at risk of non-remission following CBT for childhood anxiety.

BackgroundChildren 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.MethodsData 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.ResultsHigher 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.ConclusionsSub‐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.

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] 146, 95% CI 129 to 165, p<00001), but not immediately post-intervention. The intervention group showed significantly higher child receptive language on the caregiver report (CDI) at immediate (effect size 379, 95% CI 078 to 679, p=0028) but not at 12-month follow-up (effect size 296, 95% CI -010 to 598, p=0056). 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).

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.

BACKGROUND:Long-term effects of early, recurrent human exposure to general anaesthesia remain unknown. The Australasian Cystic Fibrosis Bronchoalveolar Lavage (ACFBAL) trial provided an opportunity to examine this issue in children randomly assigned in infancy to either repeated bronchoalveolar-lavage (BAL)-directed therapy with general anaesthesia or standard care with no planned lavages up to 5 years of age when all children received BAL-directed therapy under general anaesthesia. METHODS:This multicentre, randomised, open-label phase 4 trial (CF-GAIN) used the original ACFBAL trial randomisation at 3·6 months (SD 1·6) to BAL-directed therapy or standard-care groups to assess the impact of general anaesthesia exposures over early childhood. Children who completed the ACFBAL trial, with a mean age of 5·1 (SD 0·18) years, received standardised neurobehavioural and health-related-quality-of-life assessment and brain MRI scans between Oct 8, 2013, and June 30, 2017, at a mean age of 12·8 (SD 1·7) years at three hospitals in Australia and one hospital in New Zealand. The primary outcome was a composite score of performance on a standardised, computer-based assessment of child attention, processing speed, and response inhibition skills (Conners Continuous Performance test, second edition). Secondary outcomes included intellectual function, other neurobehavioural measures, and brain imaging as an exploratory outcome. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN 12613000057785) and is completed. FINDINGS:At 2 years, the BAL-directed therapy group (n=52) and standard-care group (n=45) had a median of 2·0 (IQR 1·0-3·0) and 0·0 (0·0-0·0) exposures, respectively. At completion of the ACFBAL trial, the BAL-directed therapy group had a median of 6·0 (4·0-9·5) exposures and the standard-care group 2·0 (1·0-4·0) exposures. At CF-GAIN completion, the BAL-directed therapy group had a median of 10·0 (IQR 6·5-14·5) exposures and the standard-care group 4·0 (3·0-7·0) exposures. Cumulative general anaesthesia exposure time was not prospectively collected but, for those with complete cumulative exposure time data to the end of the ACFBAL trial, the median cumulative exposure time for the BAL-directed therapy group (n=29) was 180 (IQR 140-285) min and for the standard-care group (n=32) was 48 (30-122) min. The mean Conners Continuous Performance test, second edition composite score was 51 (SD 8·1) in BAL-directed therapy group and 53 (8·8) in the standard-care group; difference -1·7 (95% CI -5·2 to 1·7; p=0·32) with similar performance on other neurobehavioural measures, including measures of executive function, intellectual quotient scores, and brain imaging. INTERPRETATION:Our findings suggest that repeated general anaesthesia exposure in young children with cystic fibrosis is not related to functional impairment in attention, intellectual quotient, executive function, or brain structure compared with a group with fewer and shorter cumulative anaesthesia durations. FUNDING:National Health and Medical Research Council Australia, Queensland Government Health Service and Clinical Innovation Fellowship, and the Children's Hospital Foundation Queensland.

Abstract Background Research in the neurosciences has highlighted the importance of intersubjective relationships in promoting neuromental development of the child. Children’s learning in early childhood occurs mainly in a dyadic context of an interaction with their parents: from this perspective, good dialogic parent–child communication is required to be promoted also through good educational practices. Dialogic Book-Sharing (DBS), a dialogic form of parent–child communication through the use of wordless picture books, provides a privileged ‘intersubjective’ space and is highly effective in promoting communication, language, attention, behavioural development and the parent–child relationship. DBS programme, successfully previously trialled in South Africa and the UK, will be applied for the first time in Italy for research purposes in Italian health, educational and maternal-child centres. Methods A multicentre randomised controlled trial is being conducted to evaluate DBS parenting intervention for children aged between 14 and 20 months. Parent–child dyads are randomly allocated to a book-sharing intervention group or to a wait-list control group. In the intervention, parents are trained in supportive book-sharing with their children by local staff of the centres. DBS intervention is carried out in small groups over a period of 4 weeks. Data are collected at baseline, post-intervention and at 6 months post-intervention with a questionnaire and video recording of parent–child interaction. Discussion DBS programme in early childhood could enhance the educational resources offered by Italian health, educational and maternal-child centres, in support of child’s development and parenting. DBS represents a strategic opportunity for bringing about positive effects, also in terms of prevention of socio-emotional and cognitive difficulties. As such it represents a promising response to the new social, health and educational needs of the post-COVID-19 pandemic era caused by the social isolation measures. Furthermore, the application of the DBS methodology is a way to promote the use of books, and thereby counteract the excessive use of technological devices already present in early childhood. Trial registration The trial is registered on the International Standard Randomised Controlled Trial Number database, registration number ISRCTN11755019 Registered on 2 November 2023. This is version 1 of the protocol for the trial.

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 condi-tions at post-treatment (d =-0.62, 95%CI [-0.76,-0.47], p < .001). At post-treatment, STPP was more effi-cacious 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.

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.

Shared picture-book reading is well-recognized as beneficial for children's early language development, especially where "dialogic book-sharing" techniques are used. Possible benefits of dialogic book-sharing to other aspects of child development have been little investigated, and it has not been widely studied in European populations. We conducted a randomized trial of dialogic book-sharing in Children's Centers in the UK, with parents of 2- to-4-year-old children, hypothesizing that it would benefit parenting and a range of child developmental outcomes. Intervention group parents (n = 110) received 7, weekly, group training sessions, and control parents (n = 108) the usual center input. Parenting and a range of child outcomes (language, attention, executive function, social development, and emotional-behavior difficul-ties) were assessed on 3 occasions: before, after, and 4-6 month following intervention. For all study outcomes we compared controls with each of the Intention-to-Treat population and the per-protocol population (participants attending the requisite number of sessions); and, for primary child outcomes only, the population of parents who engaged well with the intervention. There were substantial benefits of dialogic book-sharing training to parental behavior during book-sharing, especially for sensitivity and cognitive scaffolding. For all 3 sets of comparisons there were small-medium effects of on child expres-sive language, and, for the per protocol and engaged populations, similar sized effects on child receptive language and attention. There was no evidence of benefit of dialogic book-sharing for the other areas of child development; we suggest that specific intervention components need to be added to standard dialogic book-sharing to effect change in these areas.(c) 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )

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. Tweetable abstract Dilution of 6% saline to 3% maintains the benefits for lung function and prolonging time to next exacerbation in CF, but does not achieve the observed improvements with 6% saline in quality of life and delaying exacerbations requiring i.v. antibiotics https://bit.ly/44J1sMY

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.

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.

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, FEF25-75 p = 0.01) and bronchoalveolar lavage neutrophil elastase activity (FEV1/FVC% p = 0.001, FEV1 p = 0.05, FEF25-75 p = 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. (c) 2022 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

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.

Background: Home spirometry holds promise as a primary endpoint for clinical trials.Qualitative needs assessments describing the practices and perspectives of people with cystic fibrosis (PwCF), caregivers of PwCF, and research coordinators (RCs) regarding home spirometry can inform strategies for incorporating home spirometry into clinical trials.Methods: We conducted a series of focus groups that engaged PwCF, caregivers, or RCs (separately), led by an experienced facilitator and conducted via videoconference.PwCF aged 14 and older and caregivers with experience performing home spirometry were recruited through the Cystic Fibrosis Foundation (CFF) Community Voice.RCs with experience coaching home spirometry were recruited through the CFF Therapeutics Development Network from sites participating in the PROMISE study.Participants provided informed consent and completed an online survey before the focus group to describe their demographic characteristics and home spirometry devices.Focus groups elicited current experiences and barriers to and facilitators of home spirometry across six target areas, followed by discussion and prioritization.Target areas for PwCF and caregivers included research incentives, burden of procedures, reminders, remote coaching, training, and spirometry results.Target areas for RCs included participant and RC training, remote coaching, monitoring progress, participant engagement, and institution-specific issues.Qualitative analyses followed the deductive approach of template analysis [1].Common themes identified in each session were reviewed in all PwCF or RC sessions to identify areas of consensus, which were used to formulate recommendations for future clinical trials.Results: From September to November 2021, 27 PwCF and six caregivers stratified according to age and role (teens, adults aged 18-39, adults aged ≥40, caregivers) participated in seven sessions, and 24 RCs participated in five sessions.Groups identified barriers to and facilitators of use of home spirometry.Although most PwCF and caregivers found home spirometry convenient, many experienced technical barriers, reported a learning curve to home measurement, and expressed uncertainty about the quality and reliability of measurements.Major barriers that RCs identified involved tailoring participant training to individual needs, scheduling remote coaching, and performing effective coaching remotely.Participants offered age-specific recommendations in key domains: training materials and procedures (for PwCF and RCs), remote coaching, monitoring progress, maintaining engagement, and other areas, including differences in the conduct and interpretation of research versus clinical and home versus office spirometry.Conclusions: Recommendations from this qualitative needs assessment of PwCF, caregivers, and RCs regarding home spirometry in the research setting have been incorporated into the design of OUTREACH, a CFFfunded, multicenter, prospective study of the accuracy, variability, feasibility, and acceptability of home spirometry as a clinical trial endpoint.Our results can also help inform the design of future remote clinical trials.Acknowledgements: This work was supported by

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 mu g/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 azithromydn 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. Copyright (C) 2022 Published by Elsevier Ltd. All righ ts reserved.

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. 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. 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). 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.

Background: 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 randomised 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 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 behaviour scores.Intervention: The 8-week parent training intervention program consisted of weekly 90-minute sessions during which caregivers were taught and practiced dialogic book-sharing with their children. The control group received care as normal. Follow up assessments of the 4-year-old children took place 6 months after intervention and consisted of the majority of the measures performed at baseline. Receptive and expressive language was assessed pre- and post-intervention. 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 6 months post-intervention administration (4 years).Conclusion: The benefits noted in prior literature of book-sharing in infants did not appear to be demonstrated over 6 months, from 3.5 to 4 years of age, suggesting the importance of early intervention. Further research on adaptation of book-sharing for older participants is needed.