"FREED instils a bit of hope in the eating disorder community that things can change.": an investigation of clinician views on implementation facilitators and challenges from the rapid scaling of the First Episode Rapid Early Intervention for Eating Disorders programme.

Introduction: First Episode Rapid Early Intervention for Eating Disorders (FREED) is the leading eating disorder (ED) early intervention model for young people. Research has shown that it reduces the duration of untreated illness, improves clinical outcomes, and has cost savings. However, less is known about the experience of implementing FREED. This study aimed to investigate the views and experiences of adopting, implementing, and sustaining FREED from the perspective of clinical staff. Methods: Seven focus groups were conducted involving 26 clinicians. Thematic analysis was used, with the Non-Adoption, Abandonment and Challenges to Scale-up, Spread and Sustainability (The NASSS framework) framework being applied to organise subthemes and determine facilitators and barriers. The NASSS framework was also used to rate the complexity of themes as either simple (straightforward, predictable, few components), complicated (multiple interrelating components), or complex (dynamic, unpredictable, not easily divisible into constituent components). Results: There were 16 subthemes identified under seven broader themes representing each domain of the NASSS framework. Key barriers and areas of complexity included factors related to EDs as an illness (e.g., high acuity and prevalence), and organisational complexity (e.g., staffing shortages, lack of managerial/team support). Key facilitators included positive clinician/adopter attitudes, a supportive national network, and the ability for FREED to be flexible/adaptable over time. Conclusion: The FREED model appears to be desirable to clinical staff. Wider team and managerial support was perceived to be particularly important to its successful implementation, as were the national network and supervision. Key areas of complexity include staffing issues and high ED acuity/prevalence. These barriers to implementation need to be managed and investment continued to expand and improve early intervention for EDs further.

"Early intervention isn't an option, it's a necessity": learning from implementation facilitators and challenges from the rapid scaling of an early intervention eating disorders programme in England.

Introduction: The First Episode Rapid Early Intervention for Eating Disorders (FREED) service has shown promising outcomes for young people with an eating disorder, leading to national scaling and implementation across England. Between 2020 and 2023, the national implementation of FREED was supported by the Academic Health Science Networks (AHSNs), which are publicly funded organisations with the mission to spread innovations at scale and pace. This study aimed to investigate the views and experiences of AHSN programme leads on the national roll-out of FREED and the perceived sustainability of the model. Methods and results: Semi-structured interviews were conducted with 13 programme leads across the AHSNs with direct experience supporting the national implementation of FREED. Thematic analysis was adopted using a critical realist approach. Initial sub-themes were inductively generated and then organised under seven larger themes representing the domains of the Non-adoption, Abandonment, and Challenges to Scale-Up, Spread and Sustainability (NASSS) framework. Each sub-theme was classified as a facilitator and/or barrier and then each larger theme/domain was assessed for its complexity (simple, complicated, complex). Data analysis revealed 28 sub-themes, 10 identified as facilitators, 13 as barriers, and five as both. Two domains were classed as simple, three as complicated, and two as complex. Sub-themes ranged from illness-related complexities to organisational pressures. Key facilitators included a high-value proposition for FREED and a supportive network. Key barriers included staffing issues and illness-related factors that challenge early intervention. Discussion: Participants described broad support for FREED but desired sustained investment for continued provision and improving implementation fidelity. Future development areas raised by participants included enlarging the evidence base for early intervention, increasing associated training opportunities, and widening the reach of FREED. Results offer learning for early intervention in eating disorders and the scaling of new health initiatives.

Screening and brief intervention for underage drinkers.

In a 2007 report, the US Surgeon General called for health care professionals to renew efforts to reduce underage drinking. Focusing on the adolescent patient, this review provides health care professionals with recommendations for alcohol-related screening, brief intervention, and referral to treatment. MEDLINE and published reviews were used to identify relevant literature. Several brief screening methods have been shown to effectively identify underage drinkers likely to have alcohol use disorders. After diagnostic assessment when germane, the initial intervention typically focuses on education, motivation for change, and consideration of treatment options. Internet-accessible resources providing effective brief interventions are available, along with supplemental suggestions for parents. Recent changes in federal and commercial insurance reimbursement policies provide some fiscal support for these services, although rate increases and expanded applicability may be required to prompt the participation of many practitioners. Nevertheless, advances in clinical methods and progress on reimbursement policies have made screening and brief intervention for underage drinking more feasible in general health care practice.

Dihydropyrimidine dehydrogenase (DPD) rapidly regenerates after inactivation by eniluracil (GW776C85) in primary and metastatic colorectal cancer.

PURPOSE: Catabolism of 5-fluorouracil (5-FU) is primarily regulated by DPD. Inactivation of DPD using eniluracil is advantageous in that it renders 5-FU orally bioavailable with more predictable pharmacokinetics and blocks one of the major potential mechanisms of 5-FU chemoresistance. The purpose of this study was to initially document inactivation of DPD by eniluracil in primary and metastatic colorectal cancer (CRC) and then to assess the time-course of the regeneration of DPD activity in peripheral blood (and where possible, additional tissues). METHODS: Of 28 patients entered, 23 were randomized to preoperative oral eniluracil (20 mg orally twice daily) or placebo prior to definitive resection of primary or metastatic CRC. Three patients were replaced, two because they had no residual tumor on pathologic evaluation and one for not taking the study drug. Patients received eniluracil 48, 36, 24 and approximately 12 h prior to surgical resection. In a second part of the study to document tissue regeneration of DPD, the additional five patients received eniluracil 144, 132, 120 and 108 h prior to surgical resection. DPD activity was measured in normal tissues, tumors and peripheral blood mononuclear cells (PBMC). Serum eniluracil and plasma uracil concentrations were determined before and through 28 days after eniluracil dosing. Data are presented as means+/-SEM, and significance defined as P<0.05. RESULTS: Eniluracil inactivated DPD below the level of detection in primary and metastatic CRC as well as in normal tissues (0.0 pmol/min per mg protein) compared to primary tumor, metastatic tumor, PBMC, normal mucosa, and normal liver of patients receiving placebo (57+/-12, 119+/-19, 157+/-22, 77+/-12, 243+/-24 pmol/min/mg protein, respectively; P<0.05). At the time of surgery, serum eniluracil and uracil concentrations were 207+/-36 ng/ml and 2700+/-170 ng/ml in drug-treated patients. Within 6 days following treatment with eniluracil, serum eniluracil and uracil concentrations were undetectable, while DPD activity in PBMC had returned to baseline. The second group of patients (n=5) were given eniluracil 8 and 7 days prior to surgery to evaluate DPD regeneration in normal tissues and primary CRC tissue. In samples of these tissues, collected 6 days after the last eniluracil dose, DPD activity approached baseline in normal mucosa, normal liver and primary tumor (28+/-12, 94+/-23 and 20+/-8 pmol/min per mg protein, respectively). CONCLUSIONS: These results demonstrate that oral administration of eniluracil inactivated DPD below the level of detection in normal tissues as well as in primary and metastatic CRC. After discontinuation of eniluracil, DPD rapidly returned toward baseline within 6 days in PBMC, normal intestinal mucosa and normal liver.