PARTNER TRIAL II

INTRODUCTION: Cerebral palsy (CP) can now be diagnosed in infants with identified CP risk factors as early as three months of age; however, many barriers prevent equitable access to early detection pathways. The "Partnering Early to Provide for Infants At Risk of Cerebral Palsy" feasibility study (PĒPI ARC) seeks to trial a new approach to decrease inequitable health service in Aotearoa New Zealand for high-risk infants and their families. PĒPI ARC incorporates face-to-face clinics, an in-person and virtual Hub, and the use of telehealth to enable flexible access to CP assessments and support for health professionals in early CP detection...

PARTNER is a prospective, phase II-III, randomised controlled clinical trial, which recruited patients with Triple Negative Breast Cancer (TNBC)1,2 , who were gBRCA wild type (gBRCAwt)3 . Patients (n=559) were randomised on a 1:1 basis to neoadjuvant carboplatin with paclitaxel +/- olaparib 150mg twice daily, days 3 to 14, for 4 cycles (gap schedule olaparib, research arm) followed by 3 cycles of anthracycline chemotherapy before surgery. The primary endpoint was pathological complete response (pCR)4 , and secondary endpoints included event-free survival (EFS), and overall survival (OS)5 ...

BACKGROUND: Vasomotor symptoms (VMSs) associated with menopause represent a significant challenge for many patients after cancer treatment, particularly if conventional menopausal hormone therapy (MHT) is contraindicated. METHODS: The Menopause after Cancer (MAC) Study (NCT04766229) was a single-arm phase II trial examining the impact of a composite intervention consisting of (1) the use of non-hormonal pharmacotherapy to manage VMS, (2) digital cognitive behavioral therapy for insomnia (dCBT-I) using Sleepio (Big Health), (3) self-management strategies for VMS delivered via the myPatientSpace mobile application and (4) nomination of an additional support person/partner on quality of life (QoL) in women with moderate-to-severe VMS after cancer...

BACKGROUND: Adherence to self-management interventions is critical in both clinical settings and trials to ensure maximal effectiveness. This study reports how the Behaviour Change Wheel may be used to assess barriers to self-management behaviours and develop strategies to maximise adherence in a trial setting (the MEL-SELF trial of patient-led melanoma surveillance). METHODS: The Behaviour Change Wheel was applied by (i) using the Capability, Opportunity, Motivation-Behaviour (COMB) model informed by empirical and review data to identify adherence barriers, (ii) mapping identified barriers to corresponding intervention functions, and (iii) identifying appropriate behaviour change techniques and developing potential solutions using the APEASE (Affordability, Practicability, Effectiveness and cost-effectiveness, Acceptability, Side-effects and safety, Equity) criteria...

INTRODUCTION: SCALE-UP II aims to investigate the effectiveness of population health management interventions using text messaging (TM), chatbots and patient navigation (PN) in increasing the uptake of at-home COVID-19 testing among patients in historically marginalised communities, specifically, those receiving care at community health centres (CHCs). METHODS AND ANALYSIS: The trial is a multisite, randomised pragmatic clinical trial. Eligible patients are >18 years old with a primary care visit in the last 3 years at one of the participating CHCs...

BACKGROUND: Conventional oral levodopa therapy for the treatment of Parkinson's disease can be associated with variations in plasma concentrations. Levodopa infusion strategies might provide more consistent drug delivery and fewer motor fluctuations. We aimed to assess the safety and efficacy of a continuous 24 h/day subcutaneous infusion of ND0612 (a levodopa-carbidopa solution) compared with oral immediate-release levodopa-carbidopa for the treatment of motor fluctuations in people with Parkinson's disease...

BACKGROUND: The war in South Sudan has displaced more than four million people, with Uganda hosting the largest number of South Sudanese refugees. Research in Uganda has shown elevated levels of alcohol misuse and psychological distress among these refugees. The World Health Organization (WHO) has developed a trans-diagnostic scalable psychological intervention called Problem Management Plus (PM +) to reduce psychological distress among populations exposed to adversities. Our study aims to evaluate the effectiveness and cost-effectiveness of the CHANGE intervention, which builds on PM + , to also address alcohol misuse through problem-solving therapy and selected behavioural strategies for dealing with alcohol use disorders...

Neuroendocrine neoplasms represent a heterogenous group of rare tumors whose current therapeutic options show only limited efficacy. Oncolytic viruses exert their mode of action through (onco-)lysis of infected tumor cells and the induction of a systemic antitumoral immune response in a virus-induced inflammatory micromilieu. Here, we investigated the potential of our well-established second-generation suicide-gene armed oncolytic measles vaccine virus (MeV-SCD) in five human NEN cell lines. First, (i) expression of the MeV receptor CD46 and (ii) its correlation with primary infection rates were analyzed...

This study aimed at assessing a new line of treatment for lifelong premature ejaculation which is botulinum-A toxin injection into the bulbospongiosus muscle. Sixty patients with lifelong premature ejaculation were independently randomized into 2 groups; group I, 100 U botulinum-A toxin at 10 U/ml saline was injected with ultrasound guidance into the bulbospongiosus muscle and group II which was injected with similar volume of saline. The primary outcome was to compare both groups for changes in the Premature Ejaculation Profile (PEP), Intravaginal Ejaculatory Latency Time (IELT) and partner's satisfaction at 1, 3 and 6 months after intervention...

Social deficits are debilitating features of many psychiatric disorders, including autism. While time-intensive behavioral therapy is moderately effective, there are no pharmacological interventions for social deficits in autism. Many studies have attempted to treat social deficits using the neuropeptide oxytocin for its powerful neuromodulatory abilities and influence on social behaviors and cognition. However, clinical trials utilizing supplementation paradigms in which exogenous oxytocin is chronically administered independent of context have failed...

PURPOSE: The neutralizing peptibody trebananib prevents angiopoietin-1 and angiopoietin-2 from binding with Tie2 receptors, inhibiting angiogenesis and proliferation. Trebananib was combined with paclitaxel±trastuzumab in the I-SPY2 breast cancer trial. PATIENTS AND METHODS: I-SPY2, a phase II neoadjuvant trial, adaptively randomizes patients with high-risk, early-stage breast cancer to one of several experimental therapies or control based on receptor subtypes as defined by hormone receptor (HR) and HER2 status and MammaPrint risk (MP1, MP2)...

BACKGROUND: Intimate partner violence (IPV) is common globally, but there is a lack of research on how to intervene early with men who might be using IPV. Building on evidence supporting the benefits of online interventions for women victim/survivors, this study aims to test whether a healthy relationship website (BETTER MAN) is effective at improving men's help seeking, their recognition of behaviours as IPV and their readiness to change their behaviours. METHODS/DESIGN: In this two-group, pragmatic randomised controlled trial, men aged 18-50 years residing in Australia who have been in an adult intimate relationship (female, male or non-binary partner) in the past 12 months are eligible...

We propose a multi-metric flexible Bayesian framework to support efficient interim decision-making in multi-arm multi-stage phase II clinical trials. Multi-arm multi-stage phase II studies increase the efficiency of drug development, but early decisions regarding the futility or desirability of a given arm carry considerable risk since sample sizes are often low and follow-up periods may be short. Further, since intermediate outcomes based on biomarkers of treatment response are rarely perfect surrogates for the primary outcome and different trial stakeholders may have different levels of risk tolerance, a single hypothesis test is insufficient for comprehensively summarizing the state of the collected evidence...

PURPOSE: The VinelandTM Adaptive Behavior Scale is often used in autism spectrum disorder (ASD) trials. The Adaptive Behavior Composite Score (VABS-ABC) is the standardized overall score (the average of the Socialization, Communication and Daily Living skills domains), and the standardized 2-Domain Composite Score (VABS-2DC) is a novel outcome measure (average of the Socialization and Communication domains). A within-person meaningful change threshold (MCT) has not been established for the VABS-2DC...

PURPOSE: To explore, from the perspective of Study Partners (SPs; eg, caregivers) of clinical trial participants with autism spectrum disorder (ASD), any changes experienced in socialization and communication over the clinical trial, how these changes manifested, and the impact these changes had on the autistic individual, the SP, and family. This helps interpret whether changes in trial outcomes were meaningful. PATIENTS AND METHODS: Interviews were conducted with the SPs of individuals with ASD, without intellectual disability, from 2 clinical trials: 86 children (aged 5-12 years) or adolescents (aged 13-17 years) who took part in the aV1ation trial (83...

The placental transfer of antibodies that mediate bacterial clearance via phagocytes is likely important for protection against invasive group B Streptococcus (GBS) disease. A robust functional assay is essential to determine the immune correlates of protection and assist vaccine development. Using standard reagents, we developed and optimized an opsonophagocytic killing assay (OPKA) where dilutions of test sera were incubated with bacteria, baby rabbit complement (BRC) and differentiated HL60 cells (dHL60) for 30 min...

BACKGROUND: Intimate partner violence (IPV) is a prevalent social determinant of health. The US Preventive Services Task Force recommends routine IPV screening of women, but uptake remains variable. The Veterans Health Administration (VHA) initiated implementation facilitation (IF) to support integration of IPV screening programs into primary care clinics. An evaluation of IF efforts showed variability in IPV screening rates across sites. The follow-up study presented here used a Matrixed Multiple Case Study (MMCS) approach to examine the multilevel factors impacting IPV screening program implementation across sites with varying levels of implementation success...

There is a dearth of evidence indicating the effectiveness of psychological interventions targeting depression and/or posttraumatic stress disorder (PTSD) for Black women in the United States (US) exposed to intimate partner violence (IPV). We searched PubMed, MEDLINE, PsycINFO, EBSCOhost, Social Sciences, Social Sciences Full Text, Social Work Abstracts, and Cochrane databases between September 2021 and October 2022, for original studies of randomized control trials (RCTs) reporting depression and/or PTSD interventions delivered to US Black women with histories of IPV...

INTRODUCTION: Efficacious programmes require implementation at scale to maximise their public health impact. TransformUs is an efficacious behavioural and environmental intervention for increasing primary (elementary) school children's (5-12 years) physical activity and reducing their sedentary behaviour within school and home settings. This paper describes the study protocol of a 5-year effectiveness-implementation trial to assess the scalability and effectiveness of the TransformUs programme...

BACKGROUND: Despite recent significant strides towards acceptance, inclusion, and equality, members of the queer community still face alarming mental health disparities, being almost up to three times more likely to suffer from depression, anxiety, and suicidal thoughts compared with their heterosexual counterparts. These unique psychological challenges are due to discrimination, stigmatization, and identity-related struggles, and can potentially benefit from generative conversational Artificial Intelligence (AI)...