Palliative care needs of people and/or their families with serious and/or chronic health conditions in low- or middle-income country (LMIC) humanitarian settings-a systematic scoping review protocol.

BACKGROUND: Palliative care in low- or middle-income country (LMIC) humanitarian settings is a new area, experiencing a degree of increased momentum over recent years. The review contributes to this growing body of knowledge, in addition to identifying gaps for future research. The overall aim is to systematically explore the evidence on palliative care needs of patients and/or their families in LMIC humanitarian settings. METHODS: Arksey and O'Malley's (Int J Soc Res Methodol. 8:19-32, 2005) scoping review framework forms the basis of the study design, following further guidance from Levac et al. (Implement Sci 5:1-9, 2010), the Joanna Briggs Institute (JBI) Peters et al. (JBI Reviewer's Manual JBI: 406-452, 2020), and the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) from Tricco et al. (Ann Intern Med 169:467-73, 2018). This incorporates a five-step approach and the population, concept, and context (PCC) framework. Using already identified key words/terms, searches for both published research and gray literature from January 2012 to October 2022 will be undertaken using databases (likely to include Cumulative Index of Nursing and Allied Health (CINAHL), MEDLINE, Embase, Global Health, Scopus, Applied Social Science Index and Abstracts (ASSIA), Web of Science, Policy Commons, JSTOR, Library Network International Monetary Fund and World Bank, Google Advanced Search, and Google Scholar) in addition to selected pre-print sites and websites. Data selection will be undertaken based on the inclusion and exclusion criteria and will be reviewed at each stage by two reviewers, with a third to resolve any differences. Extracted data will be charted in a table. Ethical approval is not required for this review. DISCUSSION: Findings will be presented in tables and diagrams/charts, followed by a narrative description. The review will run from late October 2022 to early 2023. This is the first systematic scoping review specifically exploring the palliative care needs of patients and/or their family, in LMIC humanitarian settings. The paper from the review findings will be submitted for publication in 2023.

Prevalence and predictors of shared decision-making in goals-of-care clinician-family meetings for critically ill neurologic patients: a multi-center mixed-methods study.

BACKGROUND: Shared decision-making is a joint process where patients, or their surrogates, and clinicians make health choices based on evidence and preferences. We aimed to determine the extent and predictors of shared decision-making for goals-of-care discussions for critically ill neurological patients, which is crucial for patient-goal-concordant care but currently unknown. METHODS: We analyzed 72 audio-recorded routine clinician-family meetings during which goals-of-care were discussed from seven US hospitals. These occurred for 67 patients with 72 surrogates and 29 clinicians; one hospital provided 49/72 (68%) of the recordings. Using a previously validated 10-element shared decision-making instrument, we quantified the extent of shared decision-making in each meeting. We measured clinicians' and surrogates' characteristics and prognostic estimates for the patient's hospital survival and 6-month independent function using post-meeting questionnaires. We calculated clinician-family prognostic discordance, defined as ≥ 20% absolute difference between the clinician's and surrogate's estimates. We applied mixed-effects regression to identify independent associations with greater shared decision-making. RESULTS: The median shared decision-making score was 7 (IQR 5-8). Only 6% of meetings contained all 10 shared decision-making elements. The most common elements were "discussing uncertainty"(89%) and "assessing family understanding"(86%); least frequent elements were "assessing the need for input from others"(36%) and "eliciting the context of the decision"(33%). Clinician-family prognostic discordance was present in 60% for hospital survival and 45% for 6-month independent function. Univariate analyses indicated associations between greater shared decision-making and younger clinician age, fewer years in practice, specialty (medical-surgical critical care > internal medicine > neurocritical care > other > trauma surgery), and higher clinician-family prognostic discordance for hospital survival. After adjustment, only higher clinician-family prognostic discordance for hospital survival remained independently associated with greater shared decision-making (p = 0.029). CONCLUSION: Fewer than 1 in 10 goals-of-care clinician-family meetings for critically ill neurological patients contained all shared decision-making elements. Our findings highlight gaps in shared decision-making. Interventions promoting shared decision-making for high-stakes decisions in these patients may increase patient-value congruent care; future studies should also examine whether they will affect decision quality and surrogates' health outcomes.

Alternative splicing of the neurofibromatosis type 1 pre-mRNA is regulated by the muscleblind-like proteins and the CUG-BP and ELAV-like factors.

BACKGROUND: Alternative splicing is often subjected to complex regulatory control that involves many protein factors and cis-acting RNA sequence elements. One major challenge is to identify all of the protein players and define how they control alternative expression of a particular exon in a combinatorial manner. The Muscleblind-like (MBNL) and CUG-BP and ELAV-Like family (CELF) proteins are splicing regulatory proteins, which function as antagonists in the regulation of several alternative exons. Currently only a limited number of common targets of MBNL and CELF are known that are antagonistically regulated by these two groups of proteins. RESULTS: Recently, we identified neurofibromatosis type 1 (NF1) exon 23a as a novel target of negative regulation by CELF proteins. Here we report that MBNL family members are positive regulators of this exon. Overexpression of MBNL proteins promote exon 23a inclusion in a low MBNL-expressing cell line, and simultaneous siRNA-mediated knockdown of MBNL1 and MBNL2 family members in a high MBNL-expressing cell line promotes exon 23a skipping. Importantly, these two groups of proteins antagonize each other in regulating inclusion of exon 23a. Furthermore, we analyzed the binding sites of these proteins in the intronic sequences upstream of exon 23a by UV cross-linking assays. We show that in vitro, in addition to the previously identified preferred binding sequence UGCUGU, the MBNL proteins need the neighboring sequences for optimal binding. CONCLUSION: This study along with our previous work that demonstrated roles for Hu, CELF, and TIA-1 and TIAR proteins in the regulation of NF1 exon 23a establish that this exon is under tight, complex control.