The neonatal adverse event severity scale:current status, a stakeholders' assessment, and future perspectives

To support informed decisions on drug registration and prescription, clinical trials need tools to assess the efficacy and safety signals related to a given therapeutic intervention. Standardized assessment facilitates reproducibility of results. Furthermore, it enables weighted comparison between different interventions, instrumental to facilitate shared decisions. When focused on adverse events in clinical trials, tools are needed to assess seriousness, causality and severity. As part of such a toolbox, the international Neonatal Consortium (INC) developed a first version of the neonatal adverse event severity scale (NAESS). This version underwent subsequent validation in retro-and prospective trials to assess its applicability and impact on the inter-observer variability. Regulators, sponsors and academic researchers also reported on the use of the NAESS in regulatory documents, trial protocols and study reports. In this paper, we aim to report on the trajectory, current status and impact of the NAESS score, on how stakeholders within INC assess its relevance, and on perspectives to further develop this tool.</p

Meta-Narrative Synthesis: The Effectiveness of Diagnosing and Treating Melanoma with Micrographically Oriented Histograph Surgery MOHS Technique

This meta-narrative synthesis highlights the effectiveness of diagnosing and treating melanoma with Micrographically Oriented Histography Surgery (MOHS) technique. Initiating the questions: What techniques does MOHS surgery involve when diagnosing and treating non-metastasized Melanoma? How will it provide positive outcomes for the patient? The significance of using MOHS excision technique and diagnosis of localized facial melanoma compared to traditional cancer excision techniques is designed to remove affected tissue while preserving anatomical facial structure in an aesthetic fashion. Providing an overview of the technique’s diagnostic professional capabilities as well as its strengths, limitations, improvement for upcoming studies, and potential prognosis. Melanoma, a cancerous mutation of pigmented skin cells that quickly metastasizes, requires MOHS unique invasive surgical excision techniques. As well, a multitude of synchronous skillful dermatology surgeons and histotechnologists. MOHS comparative factors include the ability for onsite treatment and diagnosis. Individual cases that qualify for MOHS treatment include the location and development of the melanoma, histological assessment, and post-operative aid. This analysis was intended to find information on MOHS and did so utilizing a meta-analysis research process. Search parameters include the skill set of the medical professional and requirements for the surgery. The research was to investigate the involved procedures and diagnosis of non-metastasized melanoma on the face, while maintaining minimal tissue damage. Standardizing MOHS procedure and expanding access for patients seeking successful cancer removal with low risk for surgical recurrence.https://openworks.mdanderson.org/rmps24/1006/thumbnail.jp

A Qualitative Analysis of the Vaccine Intention-Behavior Relationship: Parents’ Descriptions of their Intentions, Decision-making Behavior, and Planning Processes toward HPV Vaccination

Objective: Identify factors influencing the vaccine intention-behavior relationship. Design: 445 parents who received a brief intervention to promote HPV vaccination were categorized based on their intentions post-intervention (yes/unsure/eventually/never) and subsequent adolescents’ vaccine status (yes/no). 51 of those parents participated in qualitative interviews. Main Outcome Measures: Parents described their intentions, decision-making, and planning processes toward vaccination. Framework analysis was used to analyze the data. Results: Parents in the “Yes/Yes” category were knowledgeable about HPV/vaccine, described strong, stable intentions, considered themselves the primary decision-makers about vaccination, and said they vaccinated immediately. “Yes/No” parents described strong intentions and thought their adolescent was vaccinated OR described hesitant intentions, seeking advice/agreement from others and noting barriers to vaccination without solutions. “Unsure/Yes” parents described their intentions as strengthening with information from credible sources and identified strategies for overcoming barriers. “Unsure/No” and “Eventually/No” parents had misinformation/negative beliefs regarding vaccination, described being ambivalent or non-supportive of vaccination, and cited barriers to vaccination. “Never/No” parents held negative beliefs about vaccination, described strong, stable intentions to NOT vaccinate, deferring the decision to others, and reported no planning toward vaccination. Conclusions: Intention characteristics and planning processes could moderate the vaccine intention-behavior relationship, potentially serving as targets for future vaccine strategies

Evidence-based planning and costing palliative care services for children : novel multi-method epidemiological and economic exemplar

Background: Children’s palliative care is a relatively new clinical specialty. Its nature is multi-dimensional and its delivery necessarily multi-professional. Numerous diverse public and not-for-profit organisations typically provide services and support. Because services are not centrally coordinated, they are provided in a manner that is inconsistent and incoherent. Since the first children’s hospice opened in 1982, the epidemiology of life-limiting conditions has changed with more children living longer, and many requiring transfer to adult services. Very little is known about the number of children living within any given geographical locality, costs of care, or experiences of children with ongoing palliative care needs and their families. We integrated evidence, and undertook and used novel methodological epidemiological work to develop the first evidence-based and costed commissioning exemplar. Methods: Multi-method epidemiological and economic exemplar from a health and not-for-profit organisation perspective, to estimate numbers of children under 19 years with life-limiting conditions, cost current services, determine child/parent care preferences, and cost choice of end-of-life care at home. Results: The exemplar locality (North Wales) had important gaps in service provision and the clinical network. The estimated annual total cost of current children’s palliative care was about £5.5 million; average annual care cost per child was £22,771 using 2007 prevalence estimates and £2,437- £11,045 using new 2012/13 population-based prevalence estimates. Using population-based prevalence, we estimate 2271 children with a life-limiting condition in the general exemplar population and around 501 children per year with ongoing palliative care needs in contact with hospital services. Around 24 children with a wide range of life-limiting conditions require end-of-life care per year. Choice of end-of-life care at home was requested, which is not currently universally available. We estimated a minimum (based on 1 week of end-of-life care) additional cost of £336,000 per year to provide end-of-life support at home. Were end-of-life care to span 4 weeks, the total annual additional costs increases to £536,500 (2010/11 prices). Conclusions: Findings make a significant contribution to population-based needs assessment and commissioning methodology in children’s palliative care. Further work is needed to determine with greater precision which children in the total population require access to services and when. Half of children who died 2002-7 did not have conditions that met the globally used children's palliative care condition categories, which need revision in light of findings

Myosin 6 Is Required for Iris Development and Normal Function of the Outer Retina

PURPOSE. To determine the molecular basis and the pathologic consequences of a chemically induced mutation in the translational vision research models 89 (tvrm89) mouse model with ERG defects. METHODS. Mice from a G3 N-ethyl-N-nitrosourea mutagenesis program were screened for behavioral abnormalities and defects in retinal function by ERGs. The chromosomal position for the recessive tvrm89 mutation was determined in a genome-wide linkage analysis. The critical region was refined, and candidate genes were screened by direct sequencing. The tvrm89 phenotype was characterized by circling behavior, in vivo ocular imaging, detailed ERG-based studies of the retina and RPE, and histological analysis of these structures. RESULTS. The tvrm89 mutation was localized to a region on chromosome 9 containing Myo6. Sequencing identified a TC point mutation in the codon for amino acid 480 in Myo6 that converts a leucine to a proline. This mutation does not confer a loss of protein expression levels; however, mice homozygous for the Myo6 tvrm89 mutation display an abnormal iris shape and attenuation of both strobe-flash ERGs and direct-current ERGs by 4 age weeks, neither of which is associated with photoreceptor loss. CONCLUSIONS. The tvrm89 phenotype mimics that reported for Myosin6-null mice, suggesting that the mutation confers a loss of myosin 6 protein function. The observation that homozygous Myo6 tvrm89 mice display reduced ERG a-wave and b-wave components, as well as components of the ERG attributed to RPE function, indicates that myosin 6 is necessary for the generation of proper responses of the outer retina to light

The Siren Site and the Long Transition from Archaic to Late Prehistoric Lifeways on the Eastern Edwards Plateau of Central Texas

On behalf of the Texas Department of Transportation (TxDOT), SWCA Environmental Consultants (SWCA) conducted testing and data recovery investigations at the Siren site (41WM1126), a prehistoric multi-component site in the Interstate Highway 35 right-of-way along the South Fork of the San Gabriel River in Williamson County, Texas. The work was done to fulfill TxDOT’s compliance obligations under the National Historic Preservation Act and the Antiquities Code of Texas. The testing investigations were conducted under Antiquities Permit 3834, and the subsequent data recovery was under Permit 3938. Kevin Miller served as Principal Investigator on both permits. Though the site extends far beyond the area of potential effects both horizontally and vertically, the investigations focused on Late Archaic and Late Prehistoric components within a relatively limited area that would be subject to project impacts. The investigations were conducted in February 2006. The investigations identified five isolable components that were intermittently laid down from approximately 2600 to 900 years ago. A substantial Late Prehistoric Austin phase occupation is represented by Scallorn projectile points, stone tools, burned rock, faunal materials, and radiocarbon dates from cooking features. The component feature assemblage includes a cluster of discrete, well-preserved burned rock features that range from small fire-cracked rock concentrations to a large, slab-lined feature that dominates the cluster. The underlying components include four cultural strata representing a series of phases in the final millennium or so of the long Archaic period. These components span approximately 2600 to 1500 b.p., though earlier, deeply buried components were also noted on the site. These deeper deposits were not the focus of the investigations, however, since they would not be affected by the project. The Archaic components revealed a suite of small side-notched dart points such as Ensor, Fairland, and Frio, as well as many earlier broad-bladed styles such as Castroville, Montell, Marshall, and Pedernales. These robust components contained numerous burned rock features of varying size and function, abundant tools, well-preserved faunal materials, macrobotanical remains including geophytes from several earth ovens, and a large suite of radiocarbon dates. The features include an incipient burned rock midden, burned rock clusters, a debitage reduction area, a biface cache, slab-lined hearths, basin-shaped hearths, and small circular hearths. The distributions of artifacts and features within the Archaic components across the excavation blocks showed significant variations. These differences reflect sequential components that provide a view of diachronic trends in technology, subsistence, economy, and a suite of other behaviors and activities during the long transition from Archaic to Late Prehistoric adaptations. As previously determined by the testing excavations and further substantiated by the data recovery investigations, the Siren site, most notably the Late Archaic and Late Prehistoric components, is eligible for the National Register of Historic Places under Criterion D, 36 CFR 60.4, and eligible for State Archeological Landmark designation under Criteria 1 and 2 of the Rules of Practice and Procedure for the Antiquities Code of Texas, 13 TAC 26.8. The excavations and subsequent analysis have mitigated the adverse effects of the bridge construction by recovering the vast majority of the affected components within the area of potential effect. No further archaeological work is recommended. Portions of the site outside the area of potential effects have not been fully evaluated, and any future impacts beyond the mitigated areas warrant further assessment

MTG16 regulates colonic epithelial differentiation, colitis, and tumorigenesis by repressing E protein transcription factors

Aberrant epithelial differentiation and regeneration contribute to colon pathologies, including inflammatory bowel disease (iBD) and colitis-associated cancer (CAC). Myeloid translocation gene 16 (MTG16, also known as CBFA2T3) is a transcriptional corepressor expressed in the colonic epithelium. MTG16 deficiency in mice exacerbates colitis and increases tumor burden in CAC, though the underlying mechanisms remain unclear. Here, we identified MTG16 as a central mediator of epithelial differentiation, promoting goblet and restraining enteroendocrine cell development in homeostasis and enabling regeneration following dextran sulfate sodium-induced (DSS-induced) colitis. Transcriptomic analyses implicated increased Ephrussi box-binding transcription factor (E protein) activity in MTG16-deficient colon crypts. Using a mouse model with a point mutation that attenuates MTG16:E protein interactions (Mtg16(P20ST)), we showed that MTG16 exerts control over colonic epithelial differentiation and regeneration by repressing E protein-mediated transcription. Mimicking murine colitis, MTG16 expression was increased in biopsies from patients with active IBD compared with unaffected controls. Finally, uncoupling MTG16:E protein interactions partially phenocopied the enhanced tumorigenicity of Mtg16(-/)(-) colon in the azoxymethane/DSS-induced model of CAC, indicating that MTG16 protects from tumorigenesis through additional mechanisms. Collectively, our results demonstrate that MTG16, via its repression of E protein targets. is a key regulator of cell fate decisions during colon homeostasis, colitis, and cancer.Peer reviewe

Consensus Guidelines for Perioperative Care in Neonatal Intestinal Surgery: Enhanced Recovery After Surgery (ERAS\u3csup\u3e®\u3c/sup\u3e) Society Recommendations

Background: Enhanced Recovery After Surgery (ERAS®) Society guidelines integrate evidence-based practices into multimodal care pathways that have improved outcomes in multiple adult surgical specialties. There are currently no pediatric ERAS® Society guidelines. We created an ERAS® guideline designed to enhance quality of care in neonatal intestinal resection surgery. Methods: A multidisciplinary guideline generation group defined the scope, population, and guideline topics. Systematic reviews were supplemented by targeted searching and expert identification to identify 3514 publications that were screened to develop and support recommendations. Final recommendations were determined through consensus and were assessed for evidence quality and recommendation strength. Parental input was attained throughout the process. Results: Final recommendations ranged from communication strategies to antibiotic use. Topics with poor-quality and conflicting evidence were eliminated. Several recommendations were combined. The quality of supporting evidence was variable. Seventeen final recommendations are included in the proposed guideline. Discussion: We have developed a comprehensive, evidence-based ERAS guideline for neonates undergoing intestinal resection surgery. This guideline, and its creation process, provides a foundation for future ERAS guideline development and can ultimately lead to improved perioperative care across a variety of pediatric surgical specialties

A qualitative study of health care professionals' views and experiences of paediatric advance care planning

Background Good end-of-life care planning is vital to ensure optimal care is provided for patients and their families. Two key factors are open and honest advance care planning conversations between the patient (where possible), family, and health care professionals, focusing on exploring what their future wishes are; and the development of an advance care plan document. However, in paediatric and neonatal settings, there has been little research to demonstrate how advance care planning conversations take place. This study explored health care professionals’ views and experiences of paediatric advance care planning in hospitals, community settings and hospices. MethodsA qualitative methodology was employed using purposive sampling of health care professionals involved in the end-of-life care for children aged 0–18 years known to the hospital palliative care team, and had died at least three months before, but less than 18 months prior to the study. Ethics committee approval was obtained for the study. Located in the North of England, the study involved three hospitals, a children’s hospice, and community services. Data were collected using semi-structured, digitally recorded, telephone interviews. All interviews were transcribed verbatim and subjected to thematic analysis. ResultsTwenty-one health care professionals participated, including generalist paediatric staff as well as specialist palliative care staff.Two themes were generated from the study: The timing of planning conversations, including waiting for the relationship with the family to form; the introduction of parallel planning; avoiding a crisis situation. Secondly, supporting effective conversations around advance care planning, including where to have the conversation; introducing the conversation; and how to approach the topic encompassing the value of advance care planning and documentation for families. Conclusion The timing of when to start the advance care planning conversations remains an issue for health care professionals. The value of doing it in stages and considering the environment where the conversations are held was noted. Timely planning was seen as vital to avoid difficult conversations at a crisis point and for co-ordination of care. Good advance care planning is to provide the best person-centred care for the child and experience for the family