Indirect comparisons of relative efficacy estimates of zuranolone and selective serotonin reuptake inhibitors for postpartum depression.

AIMS: Estimate relative efficacy of zuranolone, a novel oral, Food and Drug Administration-approved treatment for postpartum depression (PPD) in adults vs. selective serotonin reuptake inhibitors (SSRIs) and combination therapies used for PPD in the United States. MATERIALS AND METHODS: Randomized controlled trials (RCTs) for zuranolone and SSRIs, identified from systematic review, were used to construct evidence networks, linking via common comparator arms. Due to heterogeneity in placebo responses, matching-adjusted indirect comparison (MAIC) was applied, statistically weighting the zuranolone treatment arm of Phase 3 SKYLARK Study (NCT04442503) to the placebo arm of RCTs investigating SSRIs for PPD. MAIC outputs were applied in Bucher indirect treatment comparisons (ITCs) and network meta-analysis (NMA), using Edinburgh Postnatal Depression Scale (EPDS) and 17-item Hamilton Rating Scale for Depression (HAMD-17) change from baseline (CFB) on Days 3, 15, 28 (Month 1), 45, and last observation (Day 45, Week 12/18). RESULTS: Larger EPDS CFB was observed among zuranolone-treated vs. SSRI-treated patients from Day 15 onward. Zuranolone-treated (vs. SSRI-treated) patients exhibited 4.22-point larger reduction in EPDS by Day 15 (95% confidence interval: -6.16, -2.28) and 7.43-point larger reduction at Day 45 (-9.84, -5.02) with Bucher ITC. NMA showed EPDS reduction for zuranolone was 4.52 (-6.40, -2.65) points larger than SSRIs by Day 15 and 7.16 (-9.47, -4.85) larger at Day 45. Lack of overlap between study populations substantially reduced effective sample size post-matching, making HAMD-17 CFB analysis infeasible. LIMITATIONS: Limited population overlap between SKYLARK Study and RCTs reduced feasibility of undertaking HAMD-17 CFB ITCs and may introduce uncertainty to EPDS CFB ITC results. CONCLUSIONS: Analysis showed zuranolone-treated patients with PPD experienced greater symptom improvement than SSRI-treated patients from Day 15 onward, with largest mean difference at Day 45. Adjusting for differences between placebo arms, zuranolone may be associated with greater PPD symptom improvement (measured by EPDS) vs. SSRIs.

When a baby is diagnosed at high risk of cerebral palsy: understanding and meeting parent need.

PURPOSE: To explore the experiences and needs of parents with an infant diagnosed at risk of cerebral palsy (CP) and to receive feedback on a new online support program (Parenting Acceptance and Commitment Therapy; PACT). MATERIALS AND METHODS: Eleven parents from eight family dyads (8 mothers, 3 fathers) with infants under 24 months of age (age range 10-24 months) recently diagnosed as at risk of CP as well as fourteen clinicians participated in this qualitative study through interviews. RESULTS: Parents reported conflicting emotions and grief. Further, they reported that they wanted honesty, support and normalisation of their experiences from clinicians. Parents pointed to a gap in service delivery in terms of non-pathologising psychological support specific to their needs. Clinicians reported a lack of skills in supporting distressed parents. Parent feedback on PACT was positive, with parents receptive to the online delivery. CONCLUSIONS: Parents want acceptance without pathologisation, honesty, and flexible support. Clinicians working with children at risk of CP need training in grief awareness and support for their own coping. Health services should consider building better parental support into their systems of care.IMPLICATIONS FOR REHABILITATIONParents want clinicians to be honest, supportive and to normalise their griefClinicians in rehabilitation would benefit from up-skilling in grief supportParental support should be built into systems of care for children with cerebral palsy.

Parenting Acceptance and Commitment Therapy: An RCT of an online course with families of children with CP.

AIM: To test an online course Parenting Acceptance and Commitment Therapy (PACT) in an RCT with families of children with cerebral palsy (CP), predicting improvements in emotional availability and parent and child adjustment. METHOD: 67 families of children (2-10 years) with CP participated. Families were randomly assigned to waitlist control or PACT. Assessments at baseline, post-intervention and at six-month follow up (durability of intervention effects) focussed on emotional availability, adjustment and quality of life. Analysis consisted of repeated measure linear regression models. RESULTS: At postintervention (T2), an intervention effect was demonstrated for two aspects of observed emotional availability: parental non-intrusiveness MD = 0.68 (-0.56 to 1.92), p = 0.050 and child involvement, MD = 0.91 (-0.36 to 2.18), p = 0.011. An intervention effect was also found for the parent-reported emotional availability in terms of child involvement. Further intervention effects were found in parent-report measures of child quality of life (social wellbeing and acceptance, participation and physical health), parental mindfulness, parental acceptance, support, social connection, and meaning. No effects were found on parent or child adjustment. Analyses focussed on durability of intervention effect, collapsed across groups, indicated that effects persisted at 6 month follow up (T4). INTERPRETATION: PACT demonstrated an intervention effect for two aspects of emotional availability-parental non-intrusiveness and child involvement-as well as parental mindfulness and child quality of life. Parents reported increased comfort with the CP diagnosis, higher likelihood to seek support, higher likelihood to stay connected to others and greater meaningful living. PACT is an effective online/telehealth parenting support intervention for parents of children with CP.

Six-month follow-up of a mindfulness yoga program, MiYoga, on attention, executive function, behaviour and physical outcomes in cerebral palsy.

PURPOSE: A randomised controlled trial (RCT) of a mindfulness-based yoga program, MiYoga, for cerebral palsy (CP) demonstrated improved attention in children and decreased mindfulness in parents post-intervention. This paper evaluates the retention of treatment effects at 6-months follow-up. METHODS: 42 children with CP and their parents participated in a RCT with two groups MiYoga (n = 21) and Waitlist control group (n = 21). Waitlist control participants were offered MiYoga following the post-intervention assessment. 23 out of 42 child-parent dyads from both groups completed follow-up assessment 6-months after completing MiYoga. This paper evaluates and reports data from both groups collapsed (n = 23; MiYoga n = 11; and waitlist control n = 12; 47.8% male; mean age = 9:10 ± 2.4 years) to assess retention from post-MiYoga to follow-up and pre-MiYoga to follow-up. The primary outcome was attention, measured by Conner's Continuous Performance Test II (CCPT). Secondary outcomes included child executive function, physical function, behaviour, quality of life, child and parent mindfulness, personal wellbeing, psychological wellbeing and parent-child relationship. RESULTS: Paired t-tests showed no significant changes between post-MiYoga to follow-up and pre-MiYoga to follow-up for variables that showed an intervention effect immediately after MiYoga, namely, children's attention variables and parent's mindfulness. Paired t-tests showed that children's executive function and physical function and parent's wellbeing improved significantly from pre-MiYoga to 6-months follow-up which may potentially reflect sleeper or delayed effects of MiYoga. CONCLUSION: This study identified possible delayed or sleeper effects in children's executive function and physical function and parent's well-being.Implications for rehabilitation6-month follow-up evidence for retention of effects of MiYoga on children's attention was inconsistent; therefore, booster sessions or continued practice of MiYoga as a lifestyle option are needed to maintain an effect on attention.Because MiYoga can be practised during daily activities, it may provide additional support for children with CP, complementing standard rehabilitation options.By embedding mindfulness in children and parents' daily activities, MiYoga, could provide families with accessible and time-efficient means of learning and practicing mindfulness.

Early Intervention for Children Aged 0 to 2 Years With or at High Risk of Cerebral Palsy: International Clinical Practice Guideline Based on Systematic Reviews.

Importance: Cerebral palsy (CP) is the most common childhood physical disability. Early intervention for children younger than 2 years with or at risk of CP is critical. Now that an evidence-based guideline for early accurate diagnosis of CP exists, there is a need to summarize effective, CP-specific early intervention and conduct new trials that harness plasticity to improve function and increase participation. Our recommendations apply primarily to children at high risk of CP or with a diagnosis of CP, aged 0 to 2 years. Objective: To systematically review the best available evidence about CP-specific early interventions across 9 domains promoting motor function, cognitive skills, communication, eating and drinking, vision, sleep, managing muscle tone, musculoskeletal health, and parental support. Evidence Review: The literature was systematically searched for the best available evidence for intervention for children aged 0 to 2 years at high risk of or with CP. Databases included CINAHL, Cochrane, Embase, MEDLINE, PsycInfo, and Scopus. Systematic reviews and randomized clinical trials (RCTs) were appraised by A Measurement Tool to Assess Systematic Reviews (AMSTAR) or Cochrane Risk of Bias tools. Recommendations were formed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework and reported according to the Appraisal of Guidelines, Research, and Evaluation (AGREE) II instrument. Findings: Sixteen systematic reviews and 27 RCTs met inclusion criteria. Quality varied. Three best-practice principles were supported for the 9 domains: (1) immediate referral for intervention after a diagnosis of high risk of CP, (2) building parental capacity for attachment, and (3) parental goal-setting at the commencement of intervention. Twenty-eight recommendations (24 for and 4 against) specific to the 9 domains are supported with key evidence: motor function (4 recommendations), cognitive skills (2), communication (7), eating and drinking (2), vision (4), sleep (7), tone (1), musculoskeletal health (2), and parent support (5). Conclusions and Relevance: When a child meets the criteria of high risk of CP, intervention should start as soon as possible. Parents want an early diagnosis and treatment and support implementation as soon as possible. Early intervention builds on a critical developmental time for plasticity of developing systems. Referrals for intervention across the 9 domains should be specific as per recommendations in this guideline.

Early Parenting Acceptance and Commitment Therapy 'Early PACT' for parents of infants with cerebral palsy: a study protocol of a randomised controlled trial.

INTRODUCTION: New international clinical practice guidelines exist for identifying infants at high risk of cerebral palsy (CP) earlier: between 12 to 24 weeks corrected age, significantly earlier than previous diagnosis windows in Australia at 19 months. The earlier detection of infants at high risk of CP creates an opportunity for earlier intervention. The quality of the parent-infant relationship impacts various child outcomes, and is leveraged in other forms of intervention. This paper presents the protocol of a randomised controlled trial of an online parent support programme, Early Parenting Acceptance and Commitment Therapy (Early PACT) for families of infants identified as at high risk of CP. We predict that participating in the Early PACT programme will be associated with improvements in the parent-infant relationship, in parent mental health and well-being as well as infant behaviour and quality of life. METHODS AND ANALYSIS: This study aims to recruit 60 parents of infants (0 to 2 years old corrected age) diagnosed with CP or identified as at high risk of having CP. Participants will be randomly allocated to one of two groups: Early PACT or waitlist control (1:1). Early PACT is an online parent support programme grounded in Acceptance and Commitment Therapy (ACT). It is delivered as a course on an open source course management system called edX. Early PACT is designed to support parental adjustment and parent-infant relationship around the time of early diagnosis. Assessments will be conducted at baseline, following completion of Early PACT and at 6-month follow-up (retention). The primary outcome will be the quality of parent-child interactions as measured by the Emotional Availability Scale. Standard analysis methods for randomised controlled trial will be used to make comparisons between the two groups (Early PACT and waitlist control). Retention of effects will be examined at 6-month follow-up. ETHICS AND DISSEMINATION: This study is approved through appropriate Australian and New Zealand ethics committees (see in text) with parents providing written informed consent. Findings from this trial will be disseminated through peer-reviewed journal publications and conference presentations. TRIAL REGISTRATION DETAILS: This trial has been prospectively registered on 12 June 2018 to present (ongoing) with the Australian New Zealand Clinical Trials Registry (ACTRN12618000986279); https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=3 74 896.

Exploring the Burden of X-Linked Hypophosphataemia: An Opportunistic Qualitative Study of Patient Statements Generated During a Technology Appraisal.

INTRODUCTION: Capturing the patient experience of living with a rare disease such as X-linked hypophosphataemia (XLH) is critical for a holistic understanding of the burden of a disease. The complexity of the disease coupled with the limited population makes elicitation of the patient burden methodologically challenging. This study used qualitative information direct from patient and caregiver statements to assess the burden of XLH. METHODS: A thematic analysis was conducted on statements received during a National Institute for Health and Care Excellence (NICE) online public open consultation from 15 June to 6 July 2018. Researchers and clinical experts generated themes and codes based on expected aspects of XLH burden. Statements were independently coded by two reviewers, adding additional codes as required, and analysed by frequency and co-reporting across age groups. RESULTS: The majority of responses were submitted from UK-based patients with some from the USA and Australia, and the statements related to children, adolescents and adults. The findings suggest that the greatest burden experienced by children is associated with conventional therapy, co-reported with dosing regimen, adherence, distress and pain. During adolescence, the burden becomes increasingly complex and multi-factorial, with an increasing psychological burden. In adults, conventional therapy co-reported with bone deformity and orthopaedic surgery, as well as pain, mobility, fatigue and dental problems, featured highly. DISCUSSION: Whilst our study was opportunistic in nature, it has highlighted the clear and distinctive evolution of the burden of XLH, transitioning from being therapy-oriented in childhood to multi-factorial in adolescence, and finally to adulthood with its high impact on need for other interventions, function and mobility. This qualitative thematic analysis enhances the understanding of the symptom and treatment burden of XLH.

Experiences of children and parents in MiYoga, an embodied mindfulness yoga program for cerebral palsy: A mixed method study.

BACKGROUND AND PURPOSE: A mindfulness yoga program (MiYoga) was developed and trialled with children with cerebral palsy and their parents. This mixed-method study explores the experiences of children and parents who participated in MiYoga, to assess its acceptability, feasibility and implementation. MATERIALS AND METHODS: Of the forty-two child-parent dyads who participated in the MiYoga randomised control trial, 19 children and 22 parents were interviewed individually in a semi-structured way about their experiences of MiYoga. Participants rated their mood on a 5-point scale before and after each session and completed short questionnaires at the end of each session. RESULTS: Children and parents reported improved mood after each MiYoga session. Parents reported being more aware of their thoughts and feelings and possibly became more aware of their day-to-day mindlessness. CONCLUSION: MiYoga significantly improved children and parents' mood. Parents reported gains in awareness as well as challenges of adhering to the home practice.

Effect of mindfulness yoga programme MiYoga on attention, behaviour, and physical outcomes in cerebral palsy: a randomized controlled trial.

AIM: To investigate the efficacy of an embodied mindfulness-based movement programme (MiYoga), targeting attention in children with cerebral palsy (CP). METHOD: Total number of participants 42, with 24 boys (57.1%) and 18 girls (42.9%); mean age 9y 1mo, SD 3y; Gross Motor Function Classification System levels I=22, II=12, III=8) and their parents were randomized to either MiYoga (n=21) or waitlist comparison (n=21) groups. The primary outcome was attention postintervention measured by the Conners' Continuous Performance Test, Second Edition (CCPT). Secondary outcomes included parent and child mindfulness, child quality of life, parental well-being, child executive function, child behaviour, child physical measures, and the parent-child relationship. RESULTS: Children in the MiYoga group demonstrated significantly better attention postintervention than the waitlist comparison group, with lower inattention scores on the hit reaction time standard error (F1,33 =4.59, p=0.04, partial eta-squared [ηp2]=0.13) variable and fewer perseveration errors (F1,33 =4.60, p=0.04, ηp2=0.13) on the CCPT. Intention-to-treat analysis also revealed that sustained attention in the MiYoga group was significantly better than in the waitlist comparison group postintervention (F1,37 =5.97, p=0.02, ηp2=0.14). Parents in the MiYoga group demonstrated significantly decreased mindfulness (Mindfulness Attention Awareness Scale; F1,33 =10.130, p=0.003, ηp2=0.246). INTERPRETATION: MiYoga offers a lifestyle intervention that improves attention in children with CP. MiYoga can be considered as an additional option to standard rehabilitation to enhance attention for children with CP. WHAT THIS PAPER ADDS: MiYoga, an embodied mindfulness-based movement programme, can enhance attention (more attentive and consistent performance) in children with cerebral palsy. MiYoga had no significant effect on physical functioning.

Impact of a multiplex PCR point-of-care test for influenza A/B and respiratory syncytial virus on an acute pediatric hospital ward.

Patients with respiratory infections are often managed presumptively until confirmation of infection status. We assessed the impact of introducing the Enigma® MiniLab™ FluAB-RSV point-of-care test (POCT) on patients admitted with a suspected respiratory virus driven illness in an acute pediatric ward. This utilized a before and after design (respiratory viral seasons 2013/14 versus 2014/15). Following POCT implementation, oseltamivir prescribing increased in patients with influenza (OR = 12.7, P = 0.05, 95% CI [1.0, 153.8]). A reduction in the average reimbursement charges without a change in the length of stay was observed. Modeling suggested that laboratory test cost savings could be achieved if the POCT cost £30 and was used for screening, followed by the respiratory viral panel for RSV and influenza negative patients. A rapid POCT for influenza A/B and RSV infections in pediatric inpatients may improve oseltamivir prescribing, strengthen antimicrobial stewardship, reduce reimbursement charges and decrease laboratory costs.

MiYoga: a randomised controlled trial of a mindfulness movement programme based on hatha yoga principles for children with cerebral palsy: a study protocol.

INTRODUCTION: Cerebral palsy (CP) is the most common childhood physical disability, with life-long impacts for 1.77 in 1000 children. Although CP is primarily a physical disability, children with CP have an increased risk of experiencing cognitive difficulties, particularly attention and executive function deficits. Impairment in cognitive abilities can lead to subsequent impairment in independent functioning, education, employment and interpersonal relationships. This paper reports the protocol of a randomised controlled trial of a novel family-centred lifestyle intervention based on mindfulness and hatha yoga principles (MiYoga). MiYoga aims to enhance child and parent outcomes for children with CP. METHODS AND ANALYSIS: The aim is to recruit 36 child-parent dyads (children aged 6-16 years; bilateral or unilateral CP; Gross Motor Function Classification System I-III), who will be randomly assigned to two groups: MiYoga andwaitlistt control. The MiYoga programme will be facilitated in a group format for 8 weeks. Assessments will be administered at baseline, prior to MiYoga, following completion of MiYoga, and at 6-month follow-up (retention). The primary outcome will be the child's sustained attentional ability as measured by the Conner's Continuous Performance Test II. Other outcomes of interest for children with CP consists of attentional control, physical functioning, behavioural and well-being. For parents, the outcomes of interest are mindfulness, psychological flexibility and well-being. Data will be analysed using general linear models, specifically analysis of covariance and analysis of variance. ETHICS AND DISSEMINATION: Full ethical approval for this study has been obtained by the Children's Health Queensland Hospital and Health Service Research Ethics Committee (HREC/12/QRCH/120) and The University of Queensland (2012000993). If MiYoga is proven effective, its dissemination would assist children with CP and complement their ongoing therapy by improving the ability of the child to pay attention at school and in therapy, and alleviating environmentalstressorss for both the child and his/her parents. TRIAL REGISTRATION NUMBER: ACTRN12613000729729; Pre-results.http://www.ANZCTR.org.au/ACTRN12613000729729.aspx DATE OF TRIAL REGISTRATION: Prospectively registered on 2 July 2013-present (ongoing). FINDINGS TO DATE: Recruitment is complete. Data are still being collected at present. We aim to complete data collection by February 2017.

Performance of a Novel Point-of-Care Molecular Assay for Detection of Influenza A and B Viruses and Respiratory Syncytial Virus (Enigma MiniLab) in Children with Acute Respiratory Infection.

The performance of the Enigma MiniLab assay for influenza A and B viruses and respiratory syncytial virus (RSV) was compared to a centralized laboratory respiratory virus panel. The positive and negative percent agreement for influenza A virus, influenza B virus, and RSV were 79.2% (95% confidence interval [95% CI], 57.8 to 92.9%) and 99.4% (95% CI, 98.4 to 99.9), 100% (95% CI, 47.8 to 100%) and 100% (95% CI, 99.3 to 100%), 98.5% (95% CI, 94.6 to 99.8%) and 94.5% (95% CI, 91.9 to 96.4%), respectively.

The importance of nanoparticle shape in cancer drug delivery.

INTRODUCTION: Nanoparticles have been successfully used for cancer drug delivery since 1995. In the design of commercial nanoparticles, size and surface characteristics have been exploited to achieve efficacious delivery. However, the design of optimized drug delivery platforms for efficient delivery to disease sites with minimal off-target effects remains a major research goal. One crucial element of nanoparticle design influencing both pharmacokinetics and cell uptake is nanoparticle morphology (both size and shape). In this succinct review, the authors collate the recent literature to assess the current state of understanding of the influence of nanoparticle shape on the effectiveness of drug delivery with a special emphasis on cancer therapy. AREAS COVERED: This review draws on studies that have focused on the role of nonspherical nanoparticles used for cancer drug delivery. In particular, the authors summarize the influence of nanoparticle shape on biocirculation, biodistribution, cellular uptake and overall drug efficacy. By comparing spherical and nonspherical nanoparticles, they establish some general design principles to serve as guidelines for developing the next generation of nanocarriers for drug delivery. EXPERT OPINION: Pioneering studies on nanoparticles show that nonspherical shapes show great promise as cancer drug delivery vectors. Filamentous or worm-like micelles together with other rare morphologies such as needles or disks may become the norm for next-generation drug carriers, though at present, traditional spherical micelles remain the dominant shape of nanocarriers described in the literature due to synthesis and testing difficulties. The few reports that do exist describing nonspherical nanoparticles show a number of favorable properties that should encourage more efforts to develop facile and versatile nanoparticle synthesis methodologies with the flexibility to create different shapes, tunable sizes and adaptable surface chemistries. In addition, the authors note that there is a current lack of understanding into the factors governing (and optimizing) the inter-relationships of size, surface characteristics and shapes of many nanoparticles proposed for use in cancer therapy.