Neurodevelopmental outcomes of extremely preterm infants with bronchopulmonary dysplasia (BPD) - A retrospective cohort study.

OBJECTIVE: To investigate the neurodevelopmental outcomes for preterm infants born < 29 weeks gestation with/without bronchopulmonary dysplasia (BPD). STUDY DESIGN: Preterm infants < 29 weeks' gestation born 2007-2018 in New South Wales and the Australian Capital Territory, Australia, were included. Infants who died < 36 weeks' postmenstrual age and those with major congenital anomalies were excluded. Subjects were assessed at 18-42 months corrected age using the Bayley Scales of Infant Development, 3rd edition. RESULTS: 1436 infants without BPD (non-BPD) and 1189 infants with BPD were followed. The BPD group, 69 % infants were discharged without respiratory support (BPD1), 29 % on oxygen (BPD2) and 2 % on pressure support/tracheostomy (BPD3). Moderate neurodevelopmental impairment (NDI) was evident in 5.7 % of non-BPD infants, 11 % BPD1, 15 % BPD2, 15 % BPD3 infants. Severe NDI was seen in 1.7 % non-BPD infants, 3.4 % BPD1, 7.3 % BPD2, 35 % BPD3 infants. After adjusting for confounders, infants with BPD2 (OR 2.24, 99.9 % CI 1.25 to 5.77) or BPD3 (OR 5.99, 99.9 % CI 1.27 to 46.77) were more likely to have moderate-severe NDI compared to non-BPD infants. CONCLUSION: The majority of infants with BPD were discharged home without respiratory support and had better neurocognitive outcomes in early childhood compared to those that required home-based oxygen or respiratory support.

Clinical characteristics and outcomes of perinatal stroke in Australia: Population-based longitudinal study.

AIM: Perinatal stroke is one of the main causes of hemiplegia and seizure disorder. This study aimed to analyse the clinical characteristics and outcomes of perinatal stroke in a cohort of Australian children for its early detection. METHODS: A population-based prospective longitudinal study on perinatal stroke up to 2 years of age, was conducted from 2017 to 2019. RESULTS: Eighty-seven children with perinatal stroke included 79% (69/87) acute and 21% (18/87) presumed perinatal stroke. Seventy-four per cent (51/69) acute symptomatic perinatal strokes presented in the first 3 days of life and 78% (14/18) presumed perinatal strokes presented by 6 months of age. 62% had an arterial stroke, 29% had a venous stroke and 5% had a combined arterial and venous stroke. Unexpectedly, 35% (24/69) acute symptomatic perinatal stroke had only respiratory symptoms and 50% (9/18) presumed perinatal stroke were asymptomatic. The incidence of cerebral palsy was 29% (20/69) with acute symptomatic perinatal stroke and 72% (13/18) with presumed perinatal stroke. CONCLUSIONS: The first week of a child's life is the most critical period in terms of lifelong disability from perinatal stroke. Recognising diverse clinical presentations will ensure early diagnosis and timely intervention treatments.

A Comparison of Ductal Stenting and Surgical Shunts for Infants with Duct-Dependent Pulmonary Blood Flow: The Impact of Single Versus Biventricular Repair Pathways on Outcomes.

Ductal stenting (DS) is an alternative to the Blalock-Taussig-Thomas Shunt (BTTS) as initial palliation for congenital heart disease with duct-dependent pulmonary blood flow (DDBPF). We sought to analyze the impact of intended single ventricle (SV) and biventricular (BiV) repair pathways on the outcome of DS and BTTS in infants with DDPBF. A single-center, retrospective comparison of infants with DDPBF who underwent either DS (2012-2022) or BTTS procedures (2013-2017). Primary outcomes included all-cause mortality and risk of unplanned re-intervention. Participants were divided into four groups: 1.SV with DS, 2.SV with BTTS, 3.BiV with DS, and 4.BiV with BTTS. Fifty-one DS (SV 45%) and 86 BTTS (SV 49%) procedures were undertaken. For those who had DS, mortality was lower in the BiV compared to SV patients (BiV: 0/28, versus SV: 4/23, p = 0.04). Compared to BiV DS, BiV BTTS had a higher risk of combined death or unplanned re-intervention (HR 4.28; CI 1.25-14.60; p = 0.02). In SV participants, there was no difference for either primary outcome based on procedure type. DS was associated with shorter intensive care length of stay for SV participants (mean difference 5 days, p = 0.01) and shorter intensive care and hospital stay for BiV participants (mean difference 11 days for both outcomes, p = 0.001). There is a survival benefit for DS in BiV participants compared with DS in SV and BTTS in BiV participants. Ductal stenting is associated with a shorter intensive care and hospital length of stay.

Temporal trends, clinical characteristics, and sociodemographic profile of post-neonatally acquired cerebral palsy in Australia, 1973-2012: A population-based observational study.

AIM: To describe post-neonatally acquired (PNN) cerebral palsy (CP) in terms of temporal trends in prevalence, clinical and sociodemographic profiles, known causes and associations between causes, and sociodemographic variables. METHOD: Numerator data, a count of children with PNN-CP confirmed at 5 years of age (n = 523), was drawn from two Australian state CP registers (birth years 1973-2012). Poisson regression was used to investigate temporal trends in the prevalence of PNN-CP by 5-year intervals, calculated per 10 000 live births. Using data from all state and territory Australian CP registers (n = 469), distributions of clinical characteristics, PNN-CP causes, and sociodemographic factors were tabulated (birth years 1995-2012). χ2 and logistic regression analyses were used to assess associations between sociodemographic profile, Australian reference data, and known causes. RESULTS: A significant temporal decline in PNN-CP in Victoria (p = 0.047) and Western Australia (p = 0.033) was observed. The most common proximal causes of PNN-CP were cerebrovascular accidents (34%, n = 158), infection (25%, n = 117), and non-accidental injuries (12%, n = 58). Children born to teenage mothers, Aboriginal and/or Torres Strait Islander mothers, or children born in remote areas were over-represented in this cohort compared with reference data (all p ≤ 0.001). Infectious causes were strongly associated with teenage motherhood (odds ratio 3.0 [95% confidence interval 1.1-8.2], p = 0.028) and remote living (odds ratio 4.5 [95% confidence interval 2.0-10.2], p < 0.001). INTERPRETATION: Although prevalence of PNN-CP has declined, the over-representation of priority populations, and the relative severity of a condition that is largely preventable, suggest the need for more specific primary preventive measures and support. WHAT THIS PAPER ADDS: Prevalence of post-neonatally acquired (PNN) cerebral palsy (CP) in Australia significantly declined between 1973 and 2012. Cerebrovascular accidents are the most common proximal cause of PNN-CP. Children born in remote areas are at greater risk of PNN-CP.

Risk factors for perinatal stroke in term infants: A case-control study in Australia.

AIM: The aetiology of perinatal stroke is poorly understood. This study aimed to prospectively confirm the risk factors and identify any previously unknown variables. METHODS: A prospective case-control study was conducted in Australia. Univariate odds ratios (ORs), associated 95% confidence intervals (CIs) and multivariable logistic regression models fitted with backwards stepwise variable selection were used. RESULTS: Sixty perinatal stroke cases reported between 2017 and 2019 included 95% (57/60) with multiple risk factors. Univariate analysis identified emergency caesarean section rather than NVD (P < 0.01), low Apgar score (<7) at 1, 5 and 10 min of age (P < 0.01), resuscitation at birth (P < 0.01), abnormal cord blood gas (P < 0.01), neonatal infection/sepsis (P < 0.01), congenital heart disease (P < 0.01) and hypoglycaemia (P < 0.01) as significant risk factors. Multivariate analysis found smoking during pregnancy (OR: 1.48; 95% CI: 1.09-1.99), 1-min Apgar score < 7 (OR: 1.54; 95% CI: 1.15-2.08), 10-min Apgar score < 7 (OR: 1.26; 95% CI: 1.02-1.54) and hypoglycaemia (OR: 1.49; 95% CI: 1.07-2.06). CONCLUSIONS: Perinatal stroke is associated with multiple risk factors. Exposure to smoking, 10-min Apgar score < 7, neonatal infection and hypoglycaemia were independent risk factors. Emergency caesarean section, resuscitation at birth and abnormal cord blood gas were additional risk factors.

Cox models with time-varying covariates and partly-interval censoring-A maximum penalised likelihood approach.

Time-varying covariates can be important predictors when model based predictions are considered. A Cox model that includes time-varying covariates is usually referred to as an extended Cox model. When only right censoring is presented in the observed survival times, the conventional partial likelihood method is still applicable to estimate the regression coefficients of an extended Cox model. However, if there are interval-censored survival times, then the partial likelihood method is not directly available unless an imputation, such as the middle point imputation, is used to replaced the left- and interval-censored data. However, such imputation methods are well known for causing biases. This paper considers fitting of the extended Cox models using the maximum penalised likelihood method allowing observed survival times to be partly interval censored, where a penalty function is used to regularise the baseline hazard estimate. We present simulation studies to demonstrate the performance of our proposed method, and illustrate our method with applications to two real datasets from medical research.

Penalized likelihood estimation of a mixture cure Cox model with partly interval censoring-An application to thin melanoma.

Time-to-event data in medical studies may involve some patients who are cured and will never experience the event of interest. In practice, those cured patients are right censored. However, when data contain a cured fraction, standard survival methods such as Cox proportional hazards models can produce biased results and therefore misleading interpretations. In addition, for some outcomes, the exact time of an event is not known; instead an interval of time in which the event occurred is recorded. This article proposes a new computational approach that can deal with both the cured fraction issues and the interval censoring challenge. To do so, we extend the traditional mixture cure Cox model to accommodate data with partly interval censoring for the observed event times. The traditional method for estimation of the model parameters is based on the expectation-maximization (EM) algorithm, where the log-likelihood is maximized through an indirect complete data log-likelihood function. We propose in this article an alternative algorithm that directly optimizes the log-likelihood function. Extensive Monte Carlo simulations are conducted to demonstrate the performance of the new method over the EM algorithm. The main advantage of the new algorithm is the generation of asymptotic variance matrices for all the estimated parameters. The new method is applied to a thin melanoma dataset to predict melanoma recurrence. Various inferences, including survival and hazard function plots with point-wise confidence intervals, are presented. An R package is now available at Github and will be uploaded to R CRAN.

Biofeedback assisted relaxation training and distraction therapy for pain in children undergoing botulinum neurotoxin A injections: A crossover randomized controlled trial.

AIM: To compare biofeedback assisted relaxation training (BART) with distraction therapy for pain during botulinum neurotoxin A (BoNT-A) treatment. METHOD: This was a crossover randomized controlled trial. Eligible participants were 7 years and older with neurological conditions. Participants were randomized to receive BART or distraction during their first BoNT-A treatment, followed by the alternative intervention in their subsequent BoNT-A treatment. BART was delivered via BrightHearts, an interactive heart-rate-responsive application. Outcomes were pain (Faces Pain Scale - Revised), fear (Children's Fear Scale), and anxiety (numerical rating scale, State-Trait Anxiety Inventory). Demographics, paired t-tests, and linear mixed models were used to compare outcomes. RESULTS: Thirty-eight participants (mean [SD] age 13 years 5 months [3 years 4 months], 20 males, 34 with cerebral palsy) completed both interventions. There were non-significant differences in overall pain (mean difference - 0.05, 95% confidence interval [CI] -0.91 to 0.80, p = 0.902) and worst pain (mean difference 0.37, 95% CI -0.39 to 1.13, p = 0.334) when using BART and distraction therapy. There were non-significant differences in fear and anxiety between interventions. Younger age, heightened pre-procedural state anxiety, and Gross Motor Function Classification System levels III and IV were associated with poorer outcomes (p < 0.05). Participants who received BART before distraction therapy reported lower pain and anxiety scores during both BoNT-A treatments (p < 0.05). INTERPRETATION: Children reported similar pain when using BART and distraction therapy. Those who used BART before distraction therapy reported lower pain and anxiety during both treatments. WHAT THIS PAPER ADDS: Children reported similar pain (overall; worst) when using biofeedback assisted relaxation training (BART) and distraction therapy. Children who used BART before distraction therapy reported lower pain and anxiety over both botulinum neurotoxin A treatments. Younger age, pre-procedural state anxiety, and Gross Motor Function Classification System levels III and IV predicted a worse pain experience. Distraction therapy and BART were acceptable non-pharmacological interventions for procedural pain management.

Declining trends in birth prevalence and severity of singletons with cerebral palsy of prenatal or perinatal origin in Australia: A population-based observational study.

AIM: To investigate temporal trends in birth prevalence, disability severity, and motor type for singletons with prenatal or perinatally acquired cerebral palsy (CP). METHOD: Numerator data, number of children with CP born a singleton between 1995 and 2014, confirmed at 5 years of age, were drawn from three state registers with population-level ascertainment. Birth prevalence estimates and 95% confidence intervals (CI) were calculated per 1000 singleton live births for the three states combined, overall, by gestational age group, by dichotomized disability severity, and spastic laterality. Poisson regression models were used to analyse trends. Using data from all eight registers, trends in the proportional distribution of CP subtypes overall and stratified by gestational age were examined. RESULTS: Birth prevalence of CP declined from 1.8 (95% CI 1.6-2.0) in 1995 to 1996 to 1.2 (95% CI 1.1-1.4) in 2013 to 2014 (average 5% per 2-year epoch, p < 0.001). Declines in birth prevalence were observed across all gestational age groups with the largest decline in children born at <28 weeks (average 8% per epoch, p < 0.001). Prevalence of moderate-severe disability declined for children born at <28 and ≥37 weeks (average 11% and 7% per epoch respectively, p < 0.001). The proportions of bilateral spastic CP declined (p < 0.001) at <28 weeks (p = 0.014) and ≥37 weeks (p < 0.001). The proportion of children with dyskinesia increased (28-31 weeks: p = 0.021, 32-36 weeks: p = 0.001, and ≥37 weeks: p < 0.001). INTERPRETATION: Birth prevalence of CP and moderate-severe disability (<28 and ≥37 weeks) declined in Australian singletons between 1995 and 2014, reflecting changes in prenatal and perinatal care over time. WHAT THIS PAPER ADDS: Declines in birth prevalence of prenatal or perinatally acquired cerebral palsy were observed for singletons born in Australia between 1995 and 2014. These declines were evident across all gestational age groups. Declines in birth prevalence of moderate-severe disability were observed for children born at <28 weeks and ≥37 weeks.

Global prevalence of cerebral palsy: A systematic analysis.

AIM: To determine trends and current estimates in regional and global prevalence of cerebral palsy (CP). METHOD: A systematic analysis of data from participating CP registers/surveillance systems and population-based prevalence studies (from birth year 1995) was performed. Quality and risk of bias were assessed for both data sources. Analyses were conducted for pre-/perinatal, postnatal, neonatal, and overall CP. For each region, trends were statistically classified as increasing, decreasing, heterogeneous, or no change, and most recent prevalence estimates with 95% confidence intervals (CI) were calculated. Meta-analyses were conducted to determine current birth prevalence estimates (from birth year 2010). RESULTS: Forty-one regions from 27 countries across five continents were represented. Pre-/perinatal birth prevalence declined significantly across Europe and Australia (11 out of 14 regions), with no change in postneonatal CP. From the limited but increasing data available from regions in low- and middle-income countries (LMICs), birth prevalence for pre-/perinatal CP was as high as 3.4 per 1000 (95% CI 3.0-3.9) live births. Following meta-analyses, birth prevalence for pre-/perinatal CP in regions from high-income countries (HICs) was 1.5 per 1000 (95% CI 1.4-1.6) live births, and 1.6 per 1000 (95% CI 1.5-1.7) live births when postneonatal CP was included. INTERPRETATION: The birth prevalence estimate of CP in HICs declined to 1.6 per 1000 live births. Data available from LMICs indicated markedly higher birth prevalence. WHAT THIS PAPER ADDS: • Birth prevalence of pre-/perinatal cerebral palsy (CP) in high-income countries (HICs) is decreasing. • Current overall CP birth prevalence for HICs is 1.6 per 1000 live births. • Trends in low- and middle-income countries (LMICs) cannot currently be measured. • Current birth prevalence in LMICs is markedly higher than in HICs. • Active surveillance of CP helps to assess the impact of medical advancements and social/economic development. • Population-based data on prevalence and trends of CP are critical to inform policy.

eLearning significantly improves maternity professionals' knowledge of the congenital cytomegalovirus prevention guidelines.

AIMS: Cytomegalovirus (CMV) is a preventable cause of neurodevelopmental disability. Australian guidelines recommend that pregnant women are informed about CMV to reduce their risk of infection; however, less than 10% of maternity health professionals routinely provide prevention advice. The aim was to develop and evaluate the effectiveness of an eLearning course for midwives to improve knowledge and confidence about CMV. MATERIALS AND METHODS: Participants undertaking the course between March and November 2020 were invited to complete an evaluation questionnaire: before the course (T1), immediately after (T2) and three months post completion (T3). A linear mixed model was used to evaluate change in participant scores; P < 0.05 was considered statistically significant. RESULTS: Midwives (316/363, 87%), midwifery students (29/363, 8%) and nurses (18/363, 5%) participated. At T1 80% indicated they had not received education about CMV. Total adjusted mean scores for questionnaires completed between T1 (n = 363) and T2 (n = 238) increased significantly (from 17.2 to 22.8, P < 0.001). Limited available T3 scores (n = 27) (-1.7, P < 0.001), while lower than T2, remained higher than at T1 (+3.6, P < 0.001). Participants' awareness of CMV information resources improved from 10 to 97% from T1 to T2. Confidence in providing CMV advice increased from 6 to 95% between T1 and T2 (P < 0.001) and was maintained at T3. Almost all (99%) participants indicated they would recommend the course to colleagues. CONCLUSION: Participants who completed the eLearning course had significantly improved knowledge and confidence in providing advice about CMV. Programs targeting other maternity health professionals should be considered, to further support the implementation of the congenital CMV prevention guidelines.

Clinician Perceptions of Family-Centered Care in Pediatric and Congenital Heart Settings.

Importance: Family-centered care recognizes families as central to child health and well-being and prioritizes clinician collaboration with families to ensure optimal pediatric care and outcomes. Clinician interpersonal sensitivity and communication skills are key to this approach. Objective: To examine perceptions of and factors associated with family-centered care among clinicians working in pediatric and congenital heart care. Design, Setting, and Participants: In this cross-sectional study, participants from diverse clinical disciplines (pediatric cardiology, cardiothoracic surgery, nursing, anesthesia, neonatology, intensive care, psychology, and others), completed an online survey between June 2020 and February 2021. Participants included physicians, surgeons, nurses, and allied and mental health professionals at an Australian quaternary pediatric hospital network. Statistical analysis was performed from August 2022 to June 2023. Main Outcomes and Measures: Family-centered care across 4 domains (showing interpersonal sensitivity, treating people respectfully, providing general information, and communicating specific information) was measured using the validated Measure of Processes of Care for Service Providers. Clinician burnout (emotional exhaustion, depersonalization, and personal accomplishment), confidence responding to families' psychosocial needs, and psychological, clinical role, and sociodemographic factors were also assessed. Informed by theory, hierarchical linear regression was used to identify factors associated with family-centered care. Results: There were 212 clinicians (177 women [84.3%]; 153 nurses [72.2%], 32 physicians [15.1%], 22 allied and mental health professionals [10.4%], 5 surgeons [2.3%]; 170 [80.2%] aged 20-49 years) who participated (55% response rate). Of the 4 family-centered care domains, scores for treating people respectfully were highest and associated with greater clinician confidence responding to families' psychosocial needs (effect size [ß], 0.59 [95% CI, 0.46 to 0.72]; P < .001), lower depersonalization (ß, 0.04 [95% CI, -0.07 to -0.01]; P = .02), and a greater sense of personal accomplishment at work (ß, 0.02 [95% CI, 0.01 to 0.04]; P = 0.04). Greater interpersonal sensitivity was associated with greater confidence responding to families' psychosocial needs (ß, 0.80 [95% CI, 0.62 to 0.97]; P < .001), a greater sense of personal accomplishment at work (ß, 0.03 [95% CI, 0.01 to 0.05]; P = .04), and lower use of approach-based coping, such as problem-solving (ß, 0.37 [95% CI, -0.71 to -0.02]; P = .04). Conclusions and Relevance: In this cross-sectional study, burnout and confidence responding to families' psychosocial needs were associated with clinicians' perceptions of family-centered care. These findings suggest that targeted interventions to address these factors may benefit clinicians and also potentially strengthen the practice of family-centered care in pediatric and congenital heart settings.

MEDIC: Development and validation of a new instrument to assess emotional reactivity to medical stimuli in a representative community sample of adults.

To support investigation of the etiology and psychophysiology of medical traumatic stress, we developed a standardized set of emotionally-salient medical images, called the 'MEDical Image Collection' (MEDIC), for use in neuroimaging or psychological research. This study aimed to establish internal consistency, test re-test reliability, and congruent validity of the image set. A representative sample of 300 adults in the United States were recruited via research recruitment platform, Prolific. Participants rated 124 images depicting medical stimuli on one of two dimensions: emotional arousal (i.e., how strongly an evoked emotion is felt) or affective valence (i.e., how positive or negative the evoked emotion is). Sociodemographic and health-related characteristics, including experiences during the COVID-19 pandemic, were also assessed. To assess test re-test reliability, a subset (n = 200) rated the images on the same dimension a second time, 3 months later. The MEDIC image set was found to: (a) elicit a range of emotional arousal and valence ratings, (b) have excellent inter-rater reliability, (c) moderate test-retest reliability, and (d) good face validity. Results indicate the new MEDIC 124-image set is a reliable and valid instrument, enabling researchers to provide context-specific and emotionally-salient stimuli to individuals when studying affective responses in relation to health and medicine.

The critical need to accelerate cerebral palsy research with consumer engagement, global networks, and adaptive designs.

The prevalence of cerebral palsy (CP) varies globally, with higher rates and burden of disease in low- and middle-income countries. CP is a lifelong condition with no cure, presenting diverse challenges such as motor impairment, epilepsy, and mental health disorders. Research progress has been made but more is needed, especially given consumer demands for faster advancements and improvements in the scientific evidence base for interventions. This paper explores three strategies to accelerate CP research: consumer engagement, global clinical trial networks, and adaptive designs. Consumer engagement involving individuals with lived experience enhances research outcomes. Global clinical trial networks provide efficiency through larger and more diverse participant pools. Adaptive designs, unlike traditional randomized controlled trials, allow real-time modifications based on interim analyses, potentially answering complex questions more efficiently. The establishment of a CP Global Clinical Trials Network, integrating consumer engagement, global collaboration, and adaptive designs, marks a paradigm shift. The Network aims to address consumer-set research priorities. While challenges like ethical considerations and capacity building exist, the potential benefits for consumers, clinicians, researchers, and funding bodies are substantial. This paper underscores the urgency of transforming CP research methodologies for quicker translation of novel treatments into clinical practice to improve quality of life for those with CP.

Use of the Motor Optimality Score-Revised (MOS-R) to predict neurodevelopmental outcomes in infants with congenital anomalies.

AIMS: To describe the Motor Optimality Score-Revised (MOS-R) in infants with congenital anomalies requiring major surgery in the neonatal period; and to determine the predictive validity of the MOS-R, including specific movement and postural patterns, for neurodevelopmental outcomes at 3 years of age. METHOD: A retrospective cohort study of 201 infants born with congenital anomalies requiring surgery in the neonatal period (mean gestational age 38.2 weeks, SD 2.2). MOS-R completed using the pre-recorded General Movements Assessment (GMA) videos taken at 12 to 14 weeks post-term age (mean 12.45, SD 1.54). Developmental outcomes were assessed at 3 years of age (38.13 months, SD 1.76) using the Bayley Scales of Infant and Toddler Development (3rd ed). RESULT: The mean score for the MOS-R was 21.85 (SD 5.16), with scores ranging from 6 to 28. Fifty-six infants (27.9 %) scored within the optimal range (25-28) with only 12 % demonstrating a normal movement character. A MOS-R total score of <21 was identified as the best performing cut-off to predict a mild, moderate or severe delay or CP diagnosis with sensitivity 0.39 (95 % CI: 0.25, 0.54) and specificity 0.86 (95 % CI: 0.80, 0.91), and an area under the ROC curve of 0.63. Outcome at 3 years was significantly associated with the MOS-R total (p < 0.01) and the subscales for observed movement patterns (p < 0.01) and age adequate repertoire (p = 0.02). CONCLUSION: The MOS-R may be an effective tool to use in addition to existing assessments to identify infants who are at risk of adverse developmental outcomes. Our study found that a MOS-R of <21 identified infants who would benefit from referral to early intervention.

Out-of-pocket costs for families and people living with cerebral palsy in Australia.

The most recent cost estimates of cerebral palsy (CP) in Australia did not include out-of-pocket costs for families. This study aimed to: 1) describe and estimate out-of-pocket costs for people with CP and their families by age and gross motor function classification system (GMFCS) level; 2) measure financial distress. A cross-sectional quantitative survey design was used with qualitative approaches to analyse open-ended questions. A CP-specific out-of-pocket costs survey was co-designed with people with lived experience. Adults with CP and carers were recruited from Australian population-based CP Registers and via social media. Sociodemographic variables were analysed descriptively and median (IQR) expenses for health, assistive technology, personal care, housing, occupation, transport, leisure, respite and holidays, by age (0-6; 7-17; 18 years +) and gross motor function [GMFCS level I-II vs III-V] were calculated. The In Charge Financial Distress/Financial Wellbeing Scale measured financial distress. Regression analyses were conducted to investigate costs and financial distress. Additional out-of-pocket costs itemised in open-ended questions were charted. Comments were thematically analysed using the framework approach. 271 surveys were completed for children 0-6 years (n = 47), children/adolescents 7-17 years (n = 124) and adults (n = 100). 94% of participants had out-of-pocket costs associated with CP, with an overall annual median of $4,460 Australian dollars (IQR $11,955). After controlling for income, private insurance and disability funding, the GMFCS III-V group had costs two times higher than the GMFCS I-II group (2.01; 95% CI 1.15-3.51). Age was not significantly associated with costs. 36% of participants had high to overwhelming financial distress; this was not associated with age or GMFCS level after controlling for financial factors. Families had several additional disability costs. Open-ended responses revealed experiences of financial concern were influenced by funding scheme experiences, reduced income, uncertainty, access to support networks and an inability to afford CP-related costs. Cost estimates and financial distress indicators should inform policy, funding and clinical decisions when planning interventions to support people with CP and their families.

Proportion of Infant Neurodevelopment Trials Reporting a Null Finding: A Systematic Review.

CONTEXT: Discovering new interventions to improve neurodevelopmental outcomes is a priority; however, clinical trials are challenging and methodological issues may impact the interpretation of intervention efficacy. OBJECTIVES: Characterize the proportion of infant neurodevelopment trials reporting a null finding and identify features that may contribute to a null result. DATA SOURCES: The Cochrane library, Medline, Embase, and CINAHL databases. STUDY SELECTION: Randomized controlled trials recruiting infants aged <6 months comparing any "infant-directed" intervention against standard care, placebo, or another intervention. Neurodevelopment assessed as the primary outcome between 12 months and 10 years of age using a defined list of tools. DATA EXTRACTION: Two reviewers independently extracted data and assessed quality of included studies. RESULTS: Of n = 1283 records screened, 21 studies (from 20 reports) were included. Of 18 superiority studies, >70% reported a null finding. Features were identified that may have contributed to the high proportion of null findings, including selection and timing of the primary outcome measure, anticipated effect size, sample size and power, and statistical analysis methodology and rigor. LIMITATIONS: Publication bias against null studies means the proportion of null findings is likely underestimated. Studies assessing neurodevelopment as a secondary or within a composite outcome were excluded. CONCLUSIONS: This review identified a high proportion of infant neurodevelopmental trials that produced a null finding and detected several methodological and design considerations which may have contributed. We make several recommendations for future trials, including more sophisticated approaches to trial design, outcome assessment, and analysis.

Acceptability of neural stem cell therapy for cerebral palsy: survey of the Australian cerebral palsy community.

BACKGROUND: Neural stem cells (NSCs) have the potential to engraft and replace damaged brain tissue, repairing the damaged neonatal brain that causes cerebral palsy (CP). There are procedures that could increase engraftment of NSCs and may be critical for efficacy, but hold notable risks. Before clinical trials progress, it is important to engage with the CP community to understand their opinions. The aim of this study was to determine the acceptability of NSC therapy for CP in the CP community. METHODS: Australian residents with CP and parents/carers of those with CP completed a questionnaire to determine their willingness to use NSCs from three sources (fetal, embryonic and induced pluripotent stem cells) and their willingness to undergo accompanying procedures (neurosurgery, immunosuppression) that carry potential risks. To further explore their views, participants also answered free text questions about their ethical concerns regarding the source of NSCs and their perceptions of meaningful outcomes following NSC treatment. RESULTS: In total, 232 responses were analyzed. Participants were willing to use NSCs from all three cell sources and were willing to undergo NSC therapy despite the need for neurosurgery and immunosuppression. Participants identified a range of outcome domains considered important following NSC treatment including gross motor function, quality of life, independence and cognitive function. CONCLUSIONS: Hypothetical NSC therapy was acceptable to the Australian CP community. This study has identified important findings from the CP community which can be used to inform future NSC research, including the design of clinical trials which may help to increase recruitment, compliance and participant satisfaction.

Effectiveness of early diagnosis of cerebral palsy guideline implementation: a systematic review.

INTRODUCTION: Tailored implementation interventions are required to overcome the diagnostic research-practice gap for cerebral palsy (CP). Evaluating the impact of interventions on patient outcomes is a priority. This review aimed to summarize the established evidence for the effectiveness of guideline implementations in lowering the age of CP diagnosis. EVIDENCE ACQUISITION: A systematic review was conducted according to PRISMA. CINAHL, Embase, PubMed and MEDLINE were searched (2017-October 2022). Inclusion criteria were studies that evaluated effect of CP guideline interventions on health professional behaviour or patient outcomes. GRADE was used to determine quality. Studies were coded for use of theory (Theory Coding Scheme). Meta-analysis was performed and a standardized metric used to summarize statistics of intervention effect estimates. EVIDENCE SYNTHESIS: Of (N.=249) records screened, (N.=7) studies met inclusion, comprising interventions following infants less than 2 years of age with CP risk factors (N.=6280). Guideline feasibility in clinical practice was established through health professional adherence and patient satisfaction. Efficacy of patient outcome of CP diagnosis by 12 months of age was established in all studies. Weighted averages were: (1) high-risk of CP (N.=2) 4.2 months and (2) CP diagnosis (N.=5) at 11.6 months. Meta-analysis of (N.=2) studies found a large, pooled effect size Z = 3.00 (P=0.003) favoring implementation interventions lowering age of diagnosis by 7.50 months, however study heterogeneity was high. A paucity of theoretical frameworks were identified in this review. CONCLUSIONS: Multifaceted interventions to implement the early diagnosis of CP guideline are effective in improving patient outcomes by lowering the age of CP diagnosis in high-risk infant follow-up clinics. Further targeted health professional interventions including low-risk infant populations are warranted.

Evaluation of a Modified Mindfulness-Based Stress Reduction Intervention for Adults with Cerebral Palsy and Anxiety and/or Emotion Regulation Difficulties-A Randomised Control Trial.

Mindfulness-Based Stress Reduction (MBSR) has not yet been evaluated for people with cerebral palsy (CP). The aims of this randomised control trial were to investigate whether a modified telehealth MBSR program could improve mindfulness and reduce depression, anxiety, and emotion regulation difficulties among adults with CP with elevated anxiety and/or emotional regulation difficulties. Participants (n = 31) with elevated anxiety and/or emotion regulation difficulties and no/mild intellectual impairment were randomised to a modified telehealth MBSR program (90 min weekly, 9 weeks) group or a wait-list group. Measurements were collected prior to (T1), after (T2), and 8 weeks post-intervention (T3). The primary outcome was the mean between-group difference in the change in Cognitive and Affective Mindfulness Scale-R (CAMS-R) scores in T1-T2. The secondary outcomes included mean within-group differences over time for the CAMS-R total scores, Depression Anxiety and Stress Scale-21 subscales, and Difficulties in Emotion Regulation Scale (DERS) total t-score. We found no statistically significant between-group difference in mean change in mindfulness scores for T1-T2 (primary outcome). Secondary outcomes: The MBSR intervention group had improved CAMS-R scores with respect to T1-T2 and T1-T3; improved mean scores for Depression and Stress subscales for T1-T2; and improved DERS t-scores for T1-T2 and T1-T3. In conclusion, this study found no significant between-group difference for the primary outcome of mindfulness. The MBSR program was successfully modified for adults with CP and was effective in improving depression, stress, and emotion regulation. ACTRN12621000960853.