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Large-scale, evidence-based interventions face challenges to program fidelity of implementation. We developed implementation strategies to support teachers implementing an evidence-based HIV prevention program in schools, Focus on Youth in The Caribbean (FOYC) and Caribbean Informed Parents and Children Together (CImPACT) in The Bahamas. We examined the effects of these implementation strategies on teachers’ implementation in the subsequent year after the initial implementation during the COVID-19 pandemic. Data were collected from 79 Grade 6 teachers in 24 government elementary schools. Teachers completed training workshops and a pre-implementation questionnaire to record their characteristics and perceptions that might affect their program fidelity. School coordinators and peer mentors provided teachers with monitoring, feedback, and mentoring. In Year 1, teachers on average taught 79.3% of the sessions and 80.8% of core activities; teachers in Year 2 covered 84.2% of sessions and 72.9% of the core activities. Teachers with “good” or “excellent” school coordinators in the second year taught significantly more sessions on average (7.8 vs. 7.0, t  = 2.04, P  < 0.05) and more core activities (26.3 vs. 23.0, t  = 2.41, P  < 0.05) than teachers with “satisfactory” coordinators. Teachers who had a “good” or “satisfactory” mentor taught more sessions than teachers who did not have a mentor (7.9 vs. 7.3; t  = 2.22; P  = 0.03). Two-level mixed-effects model analysis indicated that teachers’ program fidelity in Year 1, confidence in the execution of core activities, and school coordinators’ performance were significantly associated with Year 2 implementation dose. Implementation of FOYC + CImPACT was significantly associated with improved student outcomes. Teachers maintained high fidelity to a comprehensive HIV prevention program over 2 years during the COVID-19 pandemic. Future program implementers should consider additional implementation support to improve the implementation of school-based programs.

Background There are many approaches in implementation science research and practice to prospectively and pragmatically measure the amount of effort required to implement a particular evidence-based practice (EBP). We sought to 1) demonstrate how to prospectively and pragmatically document implementation activities in a real-world implementation trial; 2) quantify implementation dose (frequency and time spent) across the implementation of four EBPs; and 3) explore potential drivers of variation in implementation dose across EBP, sites, implementation progress, and wave. Methods We built on the existing literature to develop a prospective and pragmatic way to track implementation activities during a type III hybrid effectiveness-implementation stepped wedge trial. We then quantified both total implementation dose (defined as total time spent by the implementer team) and how much of this dose was synchronous (defined as time spent working directly with local implementers at the sites receiving the intervention). We used multiple linear regression to understand what factors may influence differences in total implementation dose delivered (such as which evidence-based practice was being implemented, in which wave of the stepped wedge, at which medical centers), as well as how dose was related to implementation progress, categorized by 1) decision to participate, 2) training, 3) implementation with support, and 4) independent implementation. Results From 2022 to 2023, we prospectively captured implementation dose across 25 implementation instances related to four EBPs that were implemented at seven VA medical centers. We implemented Surgical Pause seven times, TAP six times, CAPABLE six times, and EMPOWER six times. We captured and categorized 1,271 h of implementation activities. Asynchronous administrative activities were most common across implementation phases. Other common synchronous activities include engaging collaborators, problem solving, providing updates, and ongoing action/implementation planning. The EBP was the largest driver of variation in implementation dose overall. Site, implementation progress, and wave did not independently explain variations in implementation dose. Conclusions The EBP being implemented was a much stronger predictor of the implementation dose required than were other factors, such as experience implementing the EBP or characteristics of the medical center where the intervention was being implemented.

Background Teachers’ implementation of evidence-based prevention programs in schools is inconsistent. Using data gathered from the national implementation among grade six students in The Bahamas of an evidence-based HIV intervention [Focus on Youth in the Caribbean (FOYC)], this study examines differences in the degree of implementation (“dose”) and adherence to the core activities (“fidelity of implementation”) by teachers according to theoretically and historically relevant teachers’ characteristics, attitudes, and experiences pre-intervention and post-intervention. The relationship of implementation dose and implementation fidelity is assessed according to student outcomes. Methods Beginning in 2008, the Bahamian Ministry of Education (MOE) included FOYC in the grade six curriculum nationwide. Consistent with standard practice, teachers were offered MOE training workshops in FOYC prior to delivery. The MOE conducted an anonymous curricular assessment among the grade six students at the beginning and end of the school year. Teachers agreeing to participate in the research component were asked to complete a pre-implementation and post-implementation assessment of attitudes and prior experiences. Results Teachers taught 15.6 out of 30 core activities, 24 out of the 46 total activities, and 4.6 out of 8 sessions on average. Three teachers’ implementation groups were identified: 1) High Implementation Group (31.7% of the teachers), characterized by high levels of implementation dose and fidelity of implementation; 2) Moderate Implementation Group (52.8%), showing moderate levels of implementation dose but high levels of fidelity of implementation; and 3) Low Implementation Group (15.6%), with low levels of implementation dose and fidelity of implementation. Low Implementation Group teachers compared to teachers in the two higher performing groups had less training in interactive teaching, limited prior exposure to the FOYC curriculum, incomplete attendance at FOYC training workshops, and low levels of comfort in teaching FOYC lessons. Students taught by teachers in the Low Implementation Group demonstrated poorer outcomes relevant to the four student outcomes (HIV/AIDS knowledge, preventive reproductive health skills, self-efficacy, and intention to use protection if they were to have sex). Conclusions Both implementation dose and implementation fidelity are related to student outcomes. Teachers at risk for limited implementation can be identified pre-intervention, thus opening the possibility for focused pre-intervention training.

Pharmacogenetic (PGx) guidelines for the precise dosing and selection of drugs remain poorly implemented in current clinical practice. Among the barriers to the implementation process is the lack of clinical decision support system (CDSS) tools to aid health providers in managing PGx information in the clinical context. The present study aimed to describe the first Italian endeavor to develop a PGx CDSS, called FARMAPRICE. FARMAPRICE prototype was conceived for integration of patient molecular data into the clinical prescription process in the Italian Centro di Riferimento Oncologico (CRO)-Aviano Hospital. It was developed through a coordinated partnership between two high-tech companies active in the computerization of the Italian healthcare system. Introducing FARMAPRICE into the clinical setting can aid physicians in prescribing the most efficacious and cost-effective pharmacological therapy available.

Typhoid fever is estimated to affect over 20 million people per year worldwide, with infants, children, and adolescents in south-central and southeast Asia experiencing the greatest burden of disease. The Typhoid Vaccine Acceleration Consortium (TyVAC) aims to support the introduction of typhoid conjugate vaccines into Gavi-eligible countries in an effort to reduce morbidity and mortality from typhoid. TyVAC-Nepal is a large-scale, participant- and observer-blind, individually randomized, controlled trial evaluating the efficacy of a newly developed typhoid conjugate vaccine in an urban setting in Nepal. In order to effectively deliver the trial, a number of key elements required meticulous planning. Public engagement strategies were considered early, and involved the implementation of a tiered approach. Approximately 300 staff were employed and trained in order to achieve the mass vaccination of 20 000 children aged 9 months to ≤16 years old over a 4-month period. There were 19 vaccination clinics established across the Lalitpur metropolitan city in the Kathmandu valley. Participants will be followed for 2 years post-vaccination to measure the rate reduction of blood culture–confirmed typhoid fever in the vaccination arm as compared to the control arm. The experience of conducting this large-scale vaccine trial suggests that comprehensive planning, continuous monitoring, and an ability to adapt plans in response to feedback are key.

[This corrects the article DOI: 10.3389/fphar.2024.1369805.].

Background Warfarin is a widely used oral anticoagulant. Determining the correct dose required to maintain the international normalised ratio (INR) within a therapeutic range can be challenging. In a previous trial, we showed that a dosing algorithm incorporating point-of-care genotyping information (‘POCT-GGD’ approach) led to improved anticoagulation control. To determine whether this approach could translate into clinical practice, we undertook an implementation project using a matched cohort design. Methods At three clinics (implementation group; n  = 119), initial doses were calculated using the POCT-GGD approach; at another three matched clinics (control group; n  = 93), patients were dosed according to the clinic’s routine practice. We also utilised data on 640 patients obtained from routinely collected data at comparable clinics. Primary outcome was percentage time in target INR range. Patients and staff from the implementation group also provided questionnaire feedback on POCT-GGD. Results Mean percentage time in INR target range was 55.25% in the control group and 62.74% in the implementation group; therefore, 7.49% (95% CI 3.41–11.57%) higher in the implementation group ( p  = 0.0004). Overall, patients and staff viewed POCT-GGD positively, suggesting minor adjustments to allow smooth implementation into practice. Conclusions In the first demonstration of the implementation of genotype-guided dosing, we show that warfarin dosing determined using an algorithm incorporating genetic and clinical factors can be implemented smoothly into clinic, to ensure target INR range is reached sooner and maintained. The findings are like our previous randomised controlled trial, providing an alternative method for improving the risk-benefit of warfarin use in daily practice.

Background For nearly two decades, it has been widely recognized that individuals in jail settings have a high prevalence of opioid use disorders (OUD) and are highly susceptible to fatal overdose upon their release. This setting provides a public health opportunity to address OUD with Medication for Opioid Use Disorders (MOUDs). Yet, 56% of jails do not provide MOUD, creating a pressing need for better implementation approaches in jail and the hand-off to the community. Two successful implementation strategies, NIATx external coaching and the Extension for Community Healthcare Outcomes (ECHO) case management telementoring model, were compared to address this persistent treatment gap. Methods This 2 × 2 design compared high ( n  = 12) and low ( n  = 4) dose coaching with and without ECHO in a 12-month intervention and 12 M sustainability period. The national trial included 25 jails and 13 community-based partners. MOUD trends for buprenorphine, methadone, injectable naltrexone, and combined MOUD between the study arms were assessed. Results Jail sizes ranged from 24% with < 100 and 24% with > 500 daily population, and community-based treatment providers ranged from 63% with < 50 and 7% with > 500 average monthly OUD intakes. New patient counts were found to significantly increase across the intervention phase for buprenorphine ( p  < .01) and combined MOUD ( p  < .01). Injectable naltrexone and methadone showed no consistent, significant gains. For sites with low coaching without ECHO, new patient counts for combined MOUD were predicted to increase by 47.44% during the intervention phase and 7.30% during the sustainability phase. ECHO demonstrated that MOUD use did not significantly increase compared to coaching across MOUDs in the intervention phase ( p  = .517). High- and low-dose coaching showed no significant differences in MOUD use during the intervention phase ( p  = .124). Conclusions Coaching emerged as a more effective implementation strategy than ECHO for increasing buprenorphine use in jail settings. In practice, ECHO sessions offered considerable overlap with coaching strategies. While high-dose coaching had greater gains for MOUDs overall than low-dose coaching, those gains were statistically insignificant, suggesting low-dose coaching to be more economical. To increase MOUD use in jail settings, jurisdictions should focus on new MOUDs so all three MOUDs are available and enhance the post-incarceration continuum of care. Trial registration Name of registry: ClinicalTrials.gov. Trial registration number: NCT04363320. Date of registration: 2020–07-30. URL of trial registry record: https://clinicaltrials.gov/study/NCT04363320?term=molfenter&rank=7 .

Pancreatic ductal adenocarcinoma (PDAC) is a highly devastating disease with poor prognosis and rising incidence. Late detection and a particularly aggressive biology are the major challenges which determine therapeutic failure. In this review, we present the current status and the recent advances in PDAC treatment together with the biological and immunological hallmarks of this cancer entity. On this basis, we discuss new concepts combining distinct treatment modalities in order to improve therapeutic efficacy and clinical outcome – with a specific focus on protocols involving radio(chemo)therapeutic approaches.

Background. Opioids contribute to more than 60 000 deaths annually in North America. While the expansion of overdose education and naloxone distribution (OEND) programs has been recommended in response to the opioid crisis, their effectiveness remains unclear. Objectives. To conduct an umbrella review of systematic reviews to provide a broad-based conceptual scheme of the effect and feasibility of OEND and to identify areas for possible optimization. Search Methods. We conducted the umbrella review of systematic reviews by searching PubMed, Embase, PsycINFO, Epistemonikos, the Cochrane Database of Systematic Reviews, and the reference lists of relevant articles. Briefly, an academic librarian used a 2-concept search, which included opioid subject headings and relevant keywords with a modified PubMed systematic review filter. Selection Criteria. Eligible systematic reviews described comprehensive search strategies and inclusion and exclusion criteria, evaluated the quality or risk of bias of included studies, were published in English or French, and reported data relevant to either the safety or effectiveness of OEND programs, or optimal strategies for the management of opioid overdose with naloxone in out-of-hospital settings. Data Collection and Analysis. Two reviewers independently extracted study characteristics and the quality of included reviews was assessed in duplicate with AMSTAR-2, a critical appraisal tool for systematic reviews. Review quality was rated critically low, low, moderate, or high based on 7 domains: protocol registration, literature search adequacy, exclusion criteria, risk of bias assessment, meta-analytical methods, result interpretation, and presence of publication bias. Summary tables were constructed, and confidence ratings were provided for each outcome by using a previously modified version of the Royal College of General Practitioners’ clinical guidelines. Main Results. Six systematic reviews containing 87 unique studies were included. We found that OEND programs produce long-term knowledge improvement regarding opioid overdose, improve participants’ attitudes toward naloxone, provide sufficient training for participants to safely and effectively manage overdoses, and effectively reduce opioid-related mortality. High-concentration intranasal naloxone (> 2 mg/mL) was as effective as intramuscular naloxone at the same dose, whereas lower-concentration intranasal naloxone was less effective. Evidence was limited for other naloxone formulations, as well as the need for hospital transport after overdose reversal. The preponderance of evidence pertained persons who use heroin. Author’s Conclusions. Evidence suggests that OEND programs are effective for reducing opioid-related mortality; however, additional high-quality research is required to optimize program delivery. Public Health Implications. Community-based OEND programs should be implemented widely in high-risk populations.