Lung cancer screening program factors that influence psychosocial outcomes: A systematic review.

OBJECTIVES: Lung cancer screening (LCS) programs are being designed and implemented globally. Early data suggests that the psychosocial impacts of LCS are influenced by program factors, but evidence synthesis is needed. This systematic review aimed to elucidate the impact of service-level factors on psychosocial outcomes to inform optimal LCS program design and future implementation. METHODS: Four databases were searched from inception to July 2023. Inclusion criteria were full-text articles published in English that reported an association between any program factors and psychosocial outcomes experienced during LCS. Study quality was appraised, and findings were synthesised narratively. RESULTS: Thirty-two articles were included; 29 studies were assessed at high or moderate risk of bias. Study designs were RCT (n = 3), pre-post (n = 6), cross-sectional (n = 12), mixed-methods (n = 1), and qualitative (n = 10) studies, and conducted primarily in the USA (n = 25). Findings suggested that targeted interventions can improve smoking-related or decisional psychosocial outcomes (e.g., smoking cessation interventions increase readiness/motivation to quit) but impacts of interventions on other psychological outcomes were varied. There was limited evidence reporting association between service delivery components and psychological outcomes, and results suggested moderation by individual aspects (e.g., expectation of results, baseline anxiety). Opportunities for discussion were key in reducing psychological harm. CONCLUSIONS: Certain program factors are reportedly associated with psychosocial impacts of LCS, but study heterogeneity and quality necessitate more real-world studies. Future work should examine (a) implementation of targeted interventions and high-value discussion during LCS, and (b) optimal methods and timing of risk and result communication, to improve psychosocial outcomes while reducing time burden for clinicians

Smartphone-based remote monitoring for chronic heart failure: mixed methods analysis of user experience from patient and nurse perspectives

BACKGROUND: Community-based management by heart failure specialist nurses (HFSNs) is key to improving self-care in heart failure with reduced ejection fraction. Remote monitoring (RM) can aid nurse-led management, but in the literature, user feedback evaluation is skewed in favor of the patient rather than nursing user experience. Furthermore, the ways in which different groups use the same RM platform at the same time are rarely directly compared in the literature. We present a balanced semantic analysis of user feedback from patient and nurse perspectives of Luscii, a smartphone-based RM strategy combining self-measurement of vital signs, instant messaging, and e-learning. OBJECTIVE: This study aims to (1) evaluate how patients and nurses use this type of RM (usage type), (2) evaluate patients' and nurses' user feedback on this type of RM (user experience), and (3) directly compare the usage type and user experience of patients and nurses using the same type of RM platform at the same time. METHODS: We performed a retrospective usage type and user experience evaluation of the RM platform from the perspective of both patients with heart failure with reduced ejection fraction and the HFSNs using the platform to manage them. We conducted semantic analysis of written patient feedback provided via the platform and a focus group of 6 HFSNs. Additionally, as an indirect measure of tablet adherence, self-measured vital signs (blood pressure, heart rate, and body mass) were extracted from the RM platform at onboarding and 3 months later. Paired 2-tailed t tests were used to evaluate differences between mean scores across the 2 timepoints. RESULTS: A total of 79 patients (mean age 62 years; 35%, 28/79 female) were included. Semantic analysis of usage type revealed extensive, bidirectional information exchange between patients and HFSNs using the platform. Semantic analysis of user experience demonstrates a range of positive and negative perspectives. Positive impacts included increased patient engagement, convenience for both user groups, and continuity of care. Negative impacts included information overload for patients and increased workload for nurses. After the patients used the platform for 3 months, they showed significant reductions in heart rate (P=.004) and blood pressure (P=.008) but not body mass (P=.97) compared with onboarding. CONCLUSIONS: Smartphone-based RM with messaging and e-learning facilitates bilateral information sharing between patients and nurses on a range of topics. Patient and nurse user experience is largely positive and symmetrical, but there are possible negative impacts on patient attention and nurse workload. We recommend RM providers involve patient and nurse users in platform development, including recognition of RM usage in nursing job plans

Smartphone-based remote monitoring in heart failure with reduced ejection fraction: retrospective cohort study of secondary care use and costs

BACKGROUND: Despite effective therapies, the economic burden of heart failure with reduced ejection fraction (HFrEF) is driven by frequent hospitalizations. Treatment optimization and admission avoidance rely on frequent symptom reviews and monitoring of vital signs. Remote monitoring (RM) aims to prevent admissions by facilitating early intervention, but the impact of noninvasive, smartphone-based RM of vital signs on secondary health care use and costs in the months after a new diagnosis of HFrEF is unknown. OBJECTIVE: The purpose of this study is to conduct a secondary care health use and health-economic evaluation for patients with HFrEF using smartphone-based noninvasive RM and compare it with matched controls receiving usual care without RM. METHODS: We conducted a retrospective study of 2 cohorts of newly diagnosed HFrEF patients, matched 1:1 for demographics, socioeconomic status, comorbidities, and HFrEF severity. They are (1) the RM group, with patients using the RM platform for >3 months and (2) the control group, with patients referred before RM was available who received usual heart failure care without RM. Emergency department (ED) attendance, hospital admissions, outpatient use, and the associated costs of this secondary care activity were extracted from the Discover data set for a 3-month period after diagnosis. Platform costs were added for the RM group. Secondary health care use and costs were analyzed using Kaplan-Meier event analysis and Cox proportional hazards modeling. RESULTS: A total of 146 patients (mean age 63 years; 42/146, 29% female) were included (73 in each group). The groups were well-matched for all baseline characteristics except hypertension (P=.03). RM was associated with a lower hazard of ED attendance (hazard ratio [HR] 0.43; P=.02) and unplanned admissions (HR 0.26; P=.02). There were no differences in elective admissions (HR 1.03, P=.96) or outpatient use (HR 1.40; P=.18) between the 2 groups. These differences were sustained by a univariate model controlling for hypertension. Over a 3-month period, secondary health care costs were approximately 4-fold lower in the RM group than the control group, despite the additional cost of RM itself (mean cost per patient GBP £465, US $581 vs GBP £1850, US$2313, respectively; P=.04). CONCLUSIONS: This retrospective cohort study shows that smartphone-based RM of vital signs is feasible for HFrEF. This type of RM was associated with an approximately 2-fold reduction in ED attendance and a 4-fold reduction in emergency admissions over just 3 months after a new diagnosis with HFrEF. Costs were significantly lower in the RM group without increasing outpatient demand. This type of RM could be adjunctive to standard care to reduce admissions, enabling other resources to help patients unable to use RM

Widespread translational control of fibrosis in the human heart by RNA-binding proteins

BACKGROUND: Fibrosis is a common pathology in many cardiac disorders and is driven by the activation of resident fibroblasts. The global post-transcriptional mechanisms underlying fibroblast-to-myofibroblast conversion in the heart have not been explored. METHODS: Genome-wide changes of RNA transcription and translation during human cardiac fibroblast activation were monitored with RNA sequencing and ribosome profiling. We then used an RNA-binding protein-based analyses to identify translational regulators of fibrogenic genes. The integration with cardiac ribosome occupancy levels of 30 dilated cardiomyopathy patients demonstrates that these post-transcriptional mechanisms are also active in the diseased fibrotic human heart. RESULTS: We generated nucleotide-resolution translatome data during the TGFβ1-driven cellular transition of human cardiac fibroblasts to myofibroblasts. This identified dynamic changes of RNA transcription and translation at several time points during the fibrotic response, revealing transient and early-responder genes. Remarkably, about one-third of all changes in gene expression in activated fibroblasts are subject to translational regulation and dynamic variation in ribosome occupancy affects protein abundance independent of RNA levels. Targets of RNA-binding proteins were strongly enriched in post-transcriptionally regulated genes, suggesting genes such as MBNL2 can act as translational activators or repressors. Ribosome occupancy in the hearts of patients with dilated cardiomyopathy suggested the same post-transcriptional regulatory network was underlying cardiac fibrosis. Key network hubs include RNA-binding proteins such as PUM2 and QKI that work in concert to regulate the translation of target transcripts in human diseased hearts. Furthermore, silencing of both PUM2 and QKI inhibits the transition of fibroblasts toward pro-fibrotic myofibroblasts in response to TGFβ1. CONCLUSIONS: We reveal widespread translational effects of TGFβ1 and define novel post-transcriptional regulatory networks that control the fibroblast-to-myofibroblast transition. These networks are active in human heart disease and silencing of hub genes limits fibroblast activation. Our findings show the central importance of translational control in fibrosis and highlight novel pathogenic mechanisms in heart failure

Determinants of woody encroachment and cover in African savannas

Savanna ecosystems are an integral part of the African landscape and sustain the livelihoods of millions of people. Woody encroachment in savannas is a widespread phenomenon but its causes are widely debated. We review the extensive literature on woody encroachment to help improve understanding of the possible causes and to highlight where and how future scientific efforts to fully understand these causes should be focused. Rainfall is the most important determinant of maximum woody cover across Africa, but fire and herbivory interact to reduce woody cover below the maximum at many locations. We postulate that woody encroachment is most likely driven by CO2 enrichment and propose a two-system conceptual framework, whereby mechanisms of woody encroachment differ depending on whether the savanna is a wet or dry system. In dry savannas, the increased water-use efficiency in plants relaxes precipitation-driven constraints and increases woody growth. In wet savannas, the increase of carbon allocation to tree roots results in faster recovery rates after disturbance and a greater likelihood of reaching sexual maturity. Our proposed framework can be tested using a mixture of experimental and earth observational techniques. At a local level, changes in precipitation, burning regimes or herbivory could be driving woody encroachment, but are unlikely to be the explanation of this continent-wide phenomenon

Importance of patient bed pathways and length of stay differences in predicting COVID-19 hospital bed occupancy in England.

Background: Predicting bed occupancy for hospitalised patients with COVID-19 requires understanding of length of stay (LoS) in particular bed types. LoS can vary depending on the patient’s “bed pathway” - the sequence of transfers of individual patients between bed types during a hospital stay. In this study, we characterise these pathways, and their impact on predicted hospital bed occupancy. Methods: We obtained data from University College Hospital (UCH) and the ISARIC4C COVID-19 Clinical Information Network (CO-CIN) on hospitalised patients with COVID-19 who required care in general ward or critical care (CC) beds to determine possible bed pathways and LoS. We developed a discrete-time model to examine the implications of using either bed pathways or only average LoS by bed type to forecast bed occupancy. We compared model-predicted bed occupancy to publicly available bed occupancy data on COVID-19 in England between March and August 2020. Results: In both the UCH and CO-CIN datasets, 82% of hospitalised patients with COVID-19 only received care in general ward beds. We identified four other bed pathways, present in both datasets: “Ward, CC, Ward”, “Ward, CC”, “CC” and “CC, Ward”. Mean LoS varied by bed type, pathway, and dataset, between 1.78 and 13.53 days. For UCH, we found that using bed pathways improved the accuracy of bed occupancy predictions, while only using an average LoS for each bed type underestimated true bed occupancy. However, using the CO-CIN LoS dataset we were not able to replicate past data on bed occupancy in England, suggesting regional LoS heterogeneities. Conclusions: We identified five bed pathways, with substantial variation in LoS by bed type, pathway, and geography. This might be caused by local differences in patient characteristics, clinical care strategies, or resource availability, and suggests that national LoS averages may not be appropriate for local forecasts of bed occupancy for COVID-19. Trial registration: The ISARIC WHO CCP-UK study ISRCTN66726260 was retrospectively registered on 21/04/2020 and designated an Urgent Public Health Research Study by NIHR.</p

klf2ash317 Mutant Zebrafish Do Not Recapitulate Morpholino-Induced Vascular and Haematopoietic Phenotypes.

INTRODUCTION AND OBJECTIVES: The zinc-finger transcription factor Krϋppel-like factor 2 (KLF2) transduces blood flow into molecular signals responsible for a wide range of responses within the vasculature. KLF2 maintains a healthy, quiescent endothelial phenotype. Previous studies report a range of phenotypes following morpholino antisense oligonucleotide-induced klf2a knockdown in zebrafish. Targeted genome editing is an increasingly applied method for functional assessment of candidate genes. We therefore generated a stable klf2a mutant zebrafish and characterised its cardiovascular and haematopoietic development. METHODS AND RESULTS: Using Transcription Activator-Like Effector Nucleases (TALEN) we generated a klf2a mutant (klf2ash317) with a 14bp deletion leading to a premature stop codon in exon 2. Western blotting confirmed loss of wild type Klf2a protein and the presence of a truncated protein in klf2ash317 mutants. Homozygous klf2ash317 mutants exhibit no defects in vascular patterning, survive to adulthood and are fertile, without displaying previously described morphant phenotypes such as high-output cardiac failure, reduced haematopoetic stem cell (HSC) development or impaired formation of the 5th accessory aortic arch. Homozygous klf2ash317 mutation did not reduce angiogenesis in zebrafish with homozygous mutations in von Hippel Lindau (vhl), a form of angiogenesis that is dependent on blood flow. We examined expression of three klf family members in wildtype and klf2ash317 zebrafish. We detected vascular expression of klf2b (but not klf4a or biklf/klf4b/klf17) in wildtypes but found no differences in expression that might account for the lack of phenotype in klf2ash317 mutants. klf2b morpholino knockdown did not affect heart rate or impair formation of the 5th accessory aortic arch in either wildtypes or klf2ash317 mutants. CONCLUSIONS: The klf2ash317 mutation produces a truncated Klf2a protein but, unlike morpholino induced klf2a knockdown, does not affect cardiovascular development

LINC01013 Is a determinant of fibroblast activation and encodes a novel fibroblast-activating micropeptide (Jun, 10.1007/s12265-022-10288-z, 2022)

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LINC01013 is a determinant of fibroblast activation and encodes a novel fibroblast-activating micropeptide

Myocardial fibrosis confers an almost threefold mortality risk in heart disease. There are no prognostic therapies and novel therapeutic targets are needed. Many thousands of unannotated small open reading frames (smORFs) have been identified across the genome with potential to produce micropeptides (< 100 amino acids). We sought to investigate the role of smORFs in myocardial fibroblast activation.Analysis of human cardiac atrial fibroblasts (HCFs) stimulated with profibrotic TGFβ1 using RNA sequencing (RNA-Seq) and ribosome profiling (Ribo-Seq) identified long intergenic non-coding RNA LINC01013 as TGFβ1 responsive and containing an actively translated smORF. Knockdown of LINC01013 using siRNA reduced expression of profibrotic markers at baseline and blunted their response to TGFβ1. In contrast, overexpression of a codon-optimised smORF invoked a profibrotic response comparable to that seen with TGFβ1 treatment, whilst FLAG-tagged peptide associated with the mitochondria.Together, these data support a novel LINC01013 smORF micropeptide-mediated mechanism of fibroblast activation