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ObjectivesImplementation of guideline-recommended depression screening in oncology presents numerous challenges. Implementation strategies that are responsive to local context may be critical elements of adoption and sustainment. We evaluated barriers and facilitators to implementation of a depression screening program for breast cancer patients in a community medical oncology setting as part of a cluster randomized controlled trial.MethodsGuided by the Consolidated Framework for Implementation Research, we employed qualitative methods to evaluate clinician, administrator, and patient perceptions of the program using semi-structured interviews. We used a team-coding approach for the data; thematic development focused on barriers and facilitators to implementation using a grounded theory approach. The codebook was refined through open discussions of subjectivity and unintentional bias, coding, and memo applications (including emergent coding), and the hierarchical structure and relationships of themes.ResultsWe conducted 20 interviews with 11 clinicians/administrators and 9 patients. Five major themes emerged: (1) gradual acceptance and support of the intervention and workflow; (2) compatibility with system and personal norms and goals; (3) reinforcement of the value of and need for adaptability; (4) self-efficacy within the nursing team; and (5) importance of identifying accountable front-line staff beyond leadership "champions."ConclusionsFindings suggest a high degree of acceptability and feasibility due to the selection of appropriate implementation strategies, alignment of norms and goals, and a high degree of workflow adaptability. These findings will be uniquely helpful in generating actionable, real-world knowledge to inform the design, implementation, and sustainment of guideline-recommended depression screening programs in oncology.Trial registrationClinicalTrials.gov #NCT02941614.

ImportanceImplementation of guideline-recommended depression screening in medical oncology remains challenging. Evidence suggests that multicomponent care pathways with algorithm-based referral and management are effective, yet implementation of sustainable programs remains limited and implementation-science guided approaches are understudied.ObjectiveTo evaluate the effectiveness of an implementation-strategy guided depression screening program for patients with breast cancer in a community setting.Design, setting, and participantsA pragmatic cluster randomized clinical trial conducted within Kaiser Permanente Southern California (KPSC). The trial included 6 medical centers and 1436 patients diagnosed with new primary breast cancer who had a consultation with medical oncology between October 1, 2017, through September 30, 2018. Patients were followed up through study end date of May 31, 2019.InterventionsSix medical centers in Southern California participated and were randomized 1:1 to tailored implementation strategies (intervention, 3 sites, n = 744 patients) or education-only (control, 3 sites, n = 692 patients) groups. The program consisted of screening with the 9-item Patient Health Questionnaire (PHQ-9) and algorithm-based scoring and referral to behavioral health services based on low, moderate, or high score. Clinical teams at tailored intervention sites received program education, audit, and feedback of performance data and implementation facilitation, and clinical workflows were adapted to suit local context. Education-only controls sites received program education.Main outcomes and measuresThe primary outcome was percent of eligible patients screened and referred (based on PHQ-9 score) at intervention vs control groups measured at the patient level. Secondary outcomes included outpatient health care utilization for behavioral health, primary care, oncology, urgent care, and emergency department.ResultsAll 1436 eligible patients were randomized at the center level (mean age, 61.5 years; 99% women; 18% Asian, 17% Black, 26% Hispanic, and 37% White) and were followed up to the end of the study, insurance disenrollment, or death. Groups were similar in demographic and tumor characteristics. For the primary outcome, 7.9% (59 of 744) of patients at tailored sites were referred compared with 0.1% (1 of 692) at education-only sites (difference, 7.8%; 95% CI, 5.8%-9.8%). Referrals to a behavioral health clinician were completed by 44 of 59 patients treated at the intervention sites (75%) intervention sites vs 1 of 1 patient at the education-only sites (100%). In adjusted models patients at tailored sites had significantly fewer outpatient visits in medical oncology (rate ratio, 0.86; 95% CI, 0.86-0.89; P = .001), and no significant difference in utilization of primary care, urgent care, and emergency department visits.Conclusions and relevanceAmong patients with breast cancer treated in community-based oncology practices, tailored strategies for implementation of routine depression screening compared with an education-only control group resulted in a greater proportion of referrals to behavioral care. Further research is needed to understand the clinical benefit and cost-effectiveness of this program.Trial registrationClinicalTrials.gov Identifier: NCT02941614.

In vitro-transcribed (IVT) mRNAs are modalities that can combat human disease, exemplified by their use as vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). IVT mRNAs are transfected into target cells, where they are translated into recombinant protein, and the biological activity or immunogenicity of the encoded protein exerts an intended therapeutic effect1,2. Modified ribonucleotides are commonly incorporated into therapeutic IVT mRNAs to decrease their innate immunogenicity3–5, but their effects on mRNA translation fidelity have not been fully explored. Here we demonstrate that incorporation of N1-methylpseudouridine into mRNA results in +1 ribosomal frameshifting in vitro and that cellular immunity in mice and humans to +1 frameshifted products from BNT162b2 vaccine mRNA translation occurs after vaccination. The +1 ribosome frameshifting observed is probably a consequence of N1-methylpseudouridine-induced ribosome stalling during IVT mRNA translation, with frameshifting occurring at ribosome slippery sequences. However, we demonstrate that synonymous targeting of such slippery sequences provides an effective strategy to reduce the production of frameshifted products. Overall, these data increase our understanding of how modified ribonucleotides affect the fidelity of mRNA translation, and although there are no adverse outcomes reported from mistranslation of mRNA-based SARS-CoV-2 vaccines in humans, these data highlight potential off-target effects for future mRNA-based therapeutics and demonstrate the requirement for sequence optimization.A study demonstrates that nucleotide modifications in mRNA-based therapeutics can lead to +1 ribosomal frameshifting during translation, yielding products that can trigger immune responses. [ABSTRACT FROM AUTHOR]

Objectives: Although primarily transmitted by Aedes aegypti mosquitos, Zika virus (ZIKV) can also be transmitted by blood transfusion, due to the fact that some of the infected donors can establish asymptomatic viremia. ZIKV seroprevalence in Brazilian blood donors is unknown. The main reason for this gap in the knowledge originates from the difficulty in evaluating ZIKV humoral immunity due to antigenic cross-reactivity between the different Brazilian flaviviruses and, in particular, dengue virus (DENV). The objective of this study was to evaluate the anti-ZIKV IgG prevalence in blood donors from the Northeast region of the São Paulo State, Brazil, which experienced a ZIKV outbreak in 2016.Methods: We evaluated the ZIKV seroprevalence using the NS1 anti-ZIKV IgG test (Euroimmun), followed by confirmation of the positive and borderline results using the Plaque Reduction Neutralization Test (PRNT). ZIKV seroprevalence was estimated by testing plasma samples collected in 2015 (before the ZIKV outbreak), 2016 (during the outbreak) and 2017 (after the outbreak). In order to investigate possible antigenic cross - reactivity between ZIKV and DENV we also included samples that were taken well before the ZIKV outbreak, in years 2010 and 2013.Results: The results obtained by the Euroimmun anti-ZIKV IgG test demonstrated ZIKV seroreactivity in 2015, 2016, and 2017 with prevalences of 5.3%, 12.8% and 13.2%, respectively. The inclusion of blood donor samples from 2010 to 2013, demonstrated anti-ZIKV IgG reactivity only for 2013 (1.7%). The PRNT testing of the ZIKV positive and borderline ELISA reacting samples generated positive results only for the years of 2016 and 2017 (prevalences of 5.6% and 9.1%) which coincided with the introduction of ZIKV in our region.Conclusions: Our results estimate for the first time the ZIKV seroprevalence among Brazilian blood donors from a region with apparently extensive ZIKV circulation and which, at the same time, is highly endemic for DENV. We detected relatively low ZIKV seroprevalence in blood donors from the studied region probably due to the lower intensity of the outbreak compared to other Brazilian locations. Our study adds to the global understanding of ZIKV circulation and the herd immunity of the exposed population. [ABSTRACT FROM AUTHOR]

Mangroves are one of the most human-affected coastal ecosystems, despite their important social and ecological roles, and after decades of devastation these forests continue facing different processes of conversion, threatening their global future. Brazilian mangroves are not an exception, despite the existence of severe protection legislation. Conversions to aquaculture, industrial and urban development among others, have destroyed more than 50,000 ha (about 4% of the total mangrove area in the country) over the past three decades. Restoration efforts have somewhat minimized losses, but has recuperated only a 5% of the total degraded area. Despite criticized, monospecific plantings have demonstrated return of some ecosystem structure and functioning, and seems to be a starting point in mangrove restoration. Around 70% of Brazilian mangroves are today inside preserved areas, but the effectiveness of these advances continues impaired by bureaucracy, lack of conservation policies and economic interests. We estimate the status of Brazilian mangroves and review some restoration and conservation efforts, suggesting some management measures like restoration and community-based ecosystem management. Based in a reforested stand in Northeastern Brazil, we assess the environmental cost of mangrove clearing and reforestation results. [ABSTRACT FROM AUTHOR]

Mangrove restoration is a powerful tool for reconstructing degraded tropical estuaries worldwide. The level of intervention necessary for rebuilding a mangrove area is still under study because this system is quite dynamic and some degraded areas are able to recover by themselves. We compared a Restored Area planted with Rhizophora mangle and a Self-recovered Area, to investigate how they would differ in respect to their plant and crab assemblages. In each area, 10 plots were randomly sampled for measuring tree richness, density, diameter at breast height and biomass, as well as crab richness and density after five years from recover. Plant height and biomass, as well as crab density, were significantly higher in the Restored in relation to the Self-recovered Area. However, tree richness was higher in the Self-recovered Area and crab assemblage reached in five years a similar composition in assisted, naturally recovered and natural areas, showing the high resilience of this important functional group. Active planting of R. mangle propagules can significantly improve mangrove recovery in sites with high propagule predation, increasing tree biomass and accelerating the return of animal functional groups such as crabs. However, if resources for active restoration are scarce, passive recovery can be a successful low cost alternative for mangrove restoration that preserves tree diversity and crab assemblages. [ABSTRACT FROM AUTHOR]

Pulmonary embolism can be extremely difficult to diagnose based on clinical presentation. Many studies have demonstrated certain electrocardiographic patterns commonly seen in pulmonary embolism, but few have described changes consistent with ST segment elevation myocardial infarction. In this report, we describe a patient who presented to the emergency department with electrocardiographic findings consistent with an anteroseptal myocardial infarction and his subsequent clinical course. [ABSTRACT FROM AUTHOR]