Barriers and facilitators to parent-delivered interventions for children with or infants at risk of cerebral palsy. An integrative review informed by behaviour change theory.

PURPOSE: Empowering parents to deliver evidenced-based interventions improves outcomes for children with or infants at risk of cerebral palsy (CP), by integrating repetition and contextual learning into daily routines. We aimed to identify the barriers and facilitators to parent-delivered interventions and suggest practice improvements guided by behaviour change models. METHODS: Eight electronic databases were searched to identify studies presenting parent and therapist perspectives on parent-delivered interventions in CP. Included studies were critically appraised using validated checklists. Barriers and facilitators to parent-delivered interventions were identified and categorised into subcomponents of The Capability Opportunity and Motivation Model of Behaviour (COM-B), the Theoretical Domains Framework (TDF) and the Behaviour Change Wheel to formulate appropriate practice recommendations. RESULTS: Thirty-four studies were identified which mainly used qualitative or randomised control trial designs. Barriers to parent-delivery included insufficient parental knowledge, lack of confidence and time. Facilitators included staff continuity, empowering parents, efficient resource utilisation and flexible delivery. Practice recommendations emphasise realistic goal setting, tailored parental education and enhancing the coaching skills of therapists. CONCLUSIONS: Fostering parent-delivered interventions requires addressing knowledge gaps, skill and capacity of parents and therapists. Therapists forming strong alliances with parents and setting collaborative realistic goals are key to successful parent-delivered interventions.

Enhancing parents' skills and knowledge regarding CP interventions can increase their confidence (psychological capability) in actively participating in intervention delivery.Structuring services to accommodate family schedules and providing adequate resources (physical and social opportunity) reduce the burden on families and facilitate their engagement.Providing training and resources to therapists enhances their skills and knowledge (psychological capability) in coaching and educating parents effectively.Emphasizing the value of collaborative goal setting in achieving positive outcomes for the child and acknowledging progress (reflective and automatic motivation) motivates both parents and therapists to actively engage in intervention delivery.

Key measurement concepts and appropriate clinical outcome assessments in pediatric achondroplasia clinical trials.

BACKGROUND: This study aimed to identify fit-for-purpose clinical outcome assessments (COAs) to evaluate physical function, as well as social and emotional well-being in clinical trials enrolling a pediatric population with achondroplasia. Qualitative interviews lasting up to 90 min were conducted in the US with children/adolescents with achondroplasia and/or their caregivers. Interviews utilized concept elicitation methodology to explore experiences and priorities for treatment outcomes. Cognitive debriefing methodology explored relevance and understanding of selected COAs. RESULTS: Interviews (N = 36) were conducted with caregivers of children age 0-2 years (n = 8) and 3-7 years (n = 7) and child/caregiver dyads with children age 8-11 years (n = 15) and 12-17 years (n = 6). Children/caregivers identified pain, short stature, impacts on physical functioning, and impacts on well-being (e.g. negative attention/comments) as key bothersome aspects of achondroplasia. Caregivers considered an increase in height (n = 9/14, 64%) and an improvement in limb proportion (n = 11/14, 71%) as successful treatment outcomes. The Childhood Health Assessment Questionnaire (CHAQ) and Quality of Life in Short Stature Youth (QoLISSY-Brief) were cognitively debriefed. CHAQ items evaluating activities, reaching, and hygiene were most relevant. QoLISSY-Brief items evaluating reaching, height bother, being treated differently, and height preventing doing things others could were most relevant. The CHAQ and QoLISSY-Brief instructions, item wording, response scales/options and recall period were well understood by caregivers and adolescents age 12-17. Some children aged 8-11 had difficulty reading, understanding, or required caregiver input. Feedback informed minor amendments to the CHAQ and the addition of a 7-day recall period to the QoLISSY-Brief. These amendments were subsequently reviewed and confirmed in N = 12 interviews with caregivers of children age 0-11 (n = 9) and adolescents age 12-17 (n = 3). CONCLUSIONS: Achondroplasia impacts physical functioning and emotional/social well-being. An increase in height and improvement in limb proportion are considered to be important treatment outcomes, but children/adolescents and their caregivers expect that a successful treatment should also improve important functional outcomes such as reach. The CHAQ (adapted for achondroplasia) and QoLISSY-Brief are relevant and appropriate measures of physical function and emotional/social well-being for pediatric achondroplasia trials; patient-report is recommended for age 12-17 years and caregiver-report is recommended for age 0-11 years.

The Role of Delafloxacin in Patients with Community-Acquired Bacterial Pneumonia in the Outpatient Setting: A Budget Impact Model.

BACKGROUND AND OBJECTIVE: Community-acquired bacterial pneumonia (CABP) affects millions of people each year in the USA. The majority of patients with CABP are treated in the community setting with empirical antimicrobial therapy. Delafloxacin is an anionic fluoroquinolone approved for the treatment of adult patients with CABP. This de novo analysis sought to estimate the budget impact of delafloxacin in the treatment of adult patients with CABP in the outpatient setting from the payer's perspective. METHODS: A budget impact model (BIM) was developed from the perspective of a US third-party payer to estimate the cost of introducing delafloxacin for the outpatient treatment of CABP over a 1-year time horizon. Population, clinical, and cost inputs were based on the available literature, clinical trial data, and real-world evidence studies. Scenario analyses were conducted to evaluate the potential budget impact among COPD/asthma patients based on the findings from the phase III trial of delafloxacin for CABP, which indicated that patients with COPD or asthma may experience improved effectiveness with delafloxacin compared to moxifloxacin. RESULTS: In the base-case analysis, with a hypothetical plan of 1,000,000 members, the model estimated that adding delafloxacin to the formulary resulted in a total budget impact of $58,987. This increase was mainly attributed to treatment acquisition costs. In the scenario analysis that was restricted to COPD/asthma patients, adding delafloxacin to the formulary was estimated to result in a total budget impact of $5,042. CONCLUSION: The results of the budget impact analyses provide conservative estimates of the impact of adding delafloxacin to outpatient formularies in substitution of moxifloxacin.

The CHROME Study, a Real-world Experience of Single- and Multiple-Dose Oritavancin for Treatment of Gram-Positive Infections.

BACKGROUND: Oritavancin (ORI) is a long-acting lipoglycopeptide indicated for the treatment of adult patients with acute bacterial skin and skin structure infections (ABSSSIs) caused or suspected to be caused by susceptible Gram-positive (GP) pathogens. METHODS: Data collected from a retrospective observational program (2014-2017), Clinical and Historic Registry and Orbactiv Medical Evaluation (CHROME), describe the utilization, outcomes, and adverse events (AEs) associated with ORI in 440 patients treated at 26 US sites for ABSSSI and other GP infections. RESULTS: Clinical success in evaluable patients receiving at least 1 dose of oritavancin was 88.1% (386/438). In a subgroup of patients who received ORI for skin and soft tissue infections (n = 401) and bacteremia (n = 7), clinical success was achieved in 89.0% and 100%, respectively. A cohort of 32 patients received 2-10 ORI doses separated by no more than 14 days for complicated GP infections. Clinical success was observed in 30 of 32 patients (93.8%), including 10 of 11 (90.9%) patients with bone and joint infections and 7 of 8 (87.5%) patients with osteomyelitis. In the safety evaluable population, the overall rate of AEs was 6.6%. CONCLUSIONS: We describe results from a real-world program that includes the largest multicenter, retrospective, observational study in patients who received at least 1 dose of ORI for the treatment of GP infections. This study confirms that ORI is an effective, well-tolerated antibiotic used in single and multiple doses for the treatment of ABSSSIs and complicated GP infections.

Efficacy and Safety of Meropenem-Vaborbactam Versus Best Available Therapy for the Treatment of Carbapenem-Resistant Enterobacteriaceae Infections in Patients Without Prior Antimicrobial Failure: A Post Hoc Analysis.

INTRODUCTION: Infections due to Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae are associated with increased morbidity and high mortality. Meropenem-vaborbactam (MV) is a novel ß-lactam/ß-lactamase inhibitor combination active against KPC-producing Enterobacteriaceae. The aim of this post hoc analysis of the TANGO-II randomized controlled trial was to assess the efficacy of MV versus best available therapy (BAT) in the subgroup of patients without prior antimicrobial failure. METHODS: The primary outcome measure was clinical cure at the test of cure (TOC). Secondary outcome measures included (1) clinical cure at the end of therapy (EOT), (2) microbiological cure at TOC, (3) microbiological cure at EOT, and (4) 28-day all-cause mortality. RESULTS: First-line MV was associated with a 42.9% absolute increase in clinical cure rate at TOC (95% confidence intervals [CI] 13.7-72.1) in comparison with first-line BAT. A 49.3% absolute increase in clinical cure rate at EOT (95% CI 20.8-77.7), a 42.6% absolute increase in microbiological cure rate at EOT (95% CI 13.4-71.8), and a 36.2% absolute increase in microbiologic cure rate at TOC (95% CI 5.9-66.6) were also observed, in addition to a 29.0% absolute reduction in mortality (95% CI - 54.3 to - 3.7). Overall, fewer adverse events were observed in the MV group than in the BAT group. CONCLUSION: MV was superior to BAT in the subgroup of patients with serious carbapenem-resistant Enterobacteriaceae (CRE) infections and no prior antimicrobial failure, with very high rates of clinical success, and was well tolerated. Post approval and real-world studies remain essential to clearly define the most appropriate population for early, empirical MV coverage, in accordance with antimicrobial stewardship principles. FUNDING: The Medicines Company.