Examination of the contribution of mindfulness and catastrophising to the presence of anxiety and frequency of COPD related hospital admissions in COPD patients.

Purpose: The aim of the systematic review was to explore the role that anxiety plays in hospital admissions for those with Chronic Obstructive Pulmonary Disease (COPD). The empirical study aimed to examine whether the frequency of COPD related admissions is related to psychological factors (anxiety, depression, catastrophising, and mindfulness), disease severity, perceived disability and demographic factors. It also sought to examine whether cognitive factors (mindfulness and catastrophising) may explain unique variance in predicting anxiety and COPD-related admissions when other relevant factors are controlled for. Methods: The literature was systematically searched for research related to the predictive power of anxiety in relation to COPD related hospital admissions. A postal cross-sectional survey of 54 people with COPD examined the psychological profile of those who are admitted to hospital for COPD, and if mindfulness and catastrophising can predict anxiety and COPD hospital admissions. Correlations and multiple regressions were utilised to explore these hypotheses. Results: Fourteen studies met inclusion criteria for the systematic review, demonstrating mixed results regarding whether anxiety plays a role in COPD related hospital admissions. Findings from the empirical study suggest that a significant relationship exists between disease severity and number of COPD hospital admissions and catastrophising and overall mindfulness predicted 16.3% of variance in COPD hospital admissions (non-significant). Anxiety scores were significantly correlated with breathlessness, depression, catastrophising and mindfulness with catastrophising and mindfulness predicting 22.3% of variance in anxiety (significant). Conclusions: Further research with robust measures of anxiety and hospital utilization are needed to aid our understanding of the role of anxiety in COPD related admissions. Further research is necessary to determine if mindfulness and catastrophising are useful constructs in predicting anxiety levels and hospital admissions in those with COPD. This will help to inform future psychological interventions with this population

Combining CDKN1A gene expression and genome-wide SNPs in a twin cohort to gain insight into the heritability of individual radiosensitivity

Individual variability in response to radiation exposure is recognised and has often been reported as important in treatment planning. Despite many efforts to identify biomarkers allowing the identification of radiation sensitive patients, it is not yet possible to distinguish them with certainty before the beginning of the radiotherapy treatment. A comprehensive analysis of genome-wide single-nucleotide polymorphisms (SNPs) and a transcriptional response to ionising radiation exposure in twins have the potential to identify such an individual. In the present work, we investigated SNP profile and CDKN1A gene expression in blood T lymphocytes from 130 healthy Caucasians with a complex level of individual kinship (unrelated, mono- or dizygotic twins). It was found that genetic variation accounts for 66% (95% CI 37-82%) of CDKN1A transcriptional response to radiation exposure. We developed a novel integrative multi-kinship strategy allowing investigating the role of genome-wide polymorphisms in transcriptomic radiation response, and it revealed that rs205543 (ETV6 gene), rs2287505 and rs1263612 (KLF7 gene) are significantly associated with CDKN1A expression level. The functional analysis revealed that rs6974232 (RPA3 gene), involved in mismatch repair (p value = 9.68e-04) as well as in RNA repair (p value = 1.4e-03) might have an important role in that process. Two missense polymorphisms with possible deleterious effect in humans were identified: rs1133833 (AKIP1 gene) and rs17362588 (CCDC141 gene). In summary, the data presented here support the validity of this novel integrative data analysis strategy to provide insights into the identification of SNPs potentially influencing radiation sensitivity. Further investigations in radiation response research at the genomic level should be therefore continued to confirm these findings.Peer reviewe

Strengthening stakeholder buy-in and engagement for successful exploration and installation: A case study of the development of an area-wide, evidence-based prevention and early intervention strategy

Background: The implementation of evidence-based programmes (EBPs) designed to improve outcomes for children and young people and prevent disadvantage is an increasingly important international policy imperative. However, the integration of EBPs into existing service settings and systems is a complex and multifaceted undertaking. Methods: A process evaluation was conducted to appraise the design and development of a large-scale, areabased, prevention and early intervention initiative. This initiative, called Youngballymun, consisted of five service strategies comprising a range of EBPs (e.g. the Incredible Years Programme, Highscope) targeted at children and young people and their families (from birth to 20 years). The initiative was designed to promote the development, adoption and implementation of EBPs within routine children and youth services in a disadvantaged urban area in the Republic of Ireland. The analytical approach involved the systematic analysis and triangulation of data obtained from relevant documentation (e.g. programme manuals, meeting minutes), as well as a series of one-to-one interviews (n = 27) and six group discussions with key stakeholders (n = 29). Results: Adopting aspects of an implementation stages framework (Fixsen, Naoom, Blase, & Friedman, 2005), we examined the key implementation stages of exploration and installation. Data gathering and needs assessment and strategic organisational development played an important role in implementation. However, resistance to innovation amongst local service providers emerged as a major challenge to implementation. Factors identified as crucial to overcoming this challenge and promoting stakeholder buy-in for innovation included: encouraging and supporting stakeholder engagement; and adopting a flexible approach to implementation planning. Conclusion: Generating buy-in amongst stakeholders is central to ensuring a fit between innovative programmes and practices and the systems in which they are to be embedded. Some key lessons, such as the need for the active involvement of community-based service providers in the planning process at the earliest stages of implementation, are identified. The kinds of implementation strategies that may be used to address challenges to practice change and innovation, particularly stakeholder responsiveness to, and perceived compatibility of, EBPs, are discussed

Developing an International Register of Clinical Prediction Rules for Use in Primary Care: A Descriptive Analysis

PURPOSE: We describe the methodology used to create a register of clinical prediction rules relevant to primary care. We also summarize the rules included in the register according to various characteristics. METHODS: To identify relevant articles, we searched the MEDLINE database (PubMed) for the years 1980 to 2009 and supplemented the results with searches of secondary sources (books on clinical prediction rules) and personal resources (eg, experts in the field). The rules described in relevant articles were classified according to their clinical domain, the stage of development, and the clinical setting in which they were studied. RESULTS: Our search identified clinical prediction rules reported between 1965 and 2009. The largest share of rules (37.2%) were retrieved from PubMed. The number of published rules increased substantially over the study decades. We included 745 articles in the register; many contained more than 1 clinical prediction rule study (eg, both a derivation study and a validation study), resulting in 989 individual studies. In all, 434 unique rules had gone through derivation; however, only 54.8% had been validated and merely 2.8% had undergone analysis of their impact on either the process or outcome of clinical care. The rules most commonly pertained to cardiovascular disease, respiratory, and musculoskeletal conditions. They had most often been studied in the primary care or emergency department settings. CONCLUSIONS: Many clinical prediction rules have been derived, but only about half have been validated and few have been assessed for clinical impact. This lack of thorough evaluation for many rules makes it difficult to retrieve and identify those that are ready for use at the point of patient care. We plan to develop an international web-based register of clinical prediction rules and computer-based clinical decision support systems

Deficient Radiation Transcription Response in COVID-19 Patients

Purpose: The ongoing SARS-CoV-2 pandemic has resulted in over 6.3 million deaths and 560 million COVID-19 cases worldwide. Clinical management of hospitalized patients is complex due to the heterogeneous course of COVID-19. Low-dose radiation therapy is known to dampen localized chronic inflammation and has been suggested to be used to reduce lung inflammation in patients with COVID-19. However, it is unknown whether SARS-CoV-2 alters the radiation response and associated radiation exposure related risk.Methods and Materials: We generated gene expression profiles from circulating leukocytes of hospitalized patients with COVID-19 and healthy donors.Results: The p53 signaling pathway was found to be dysregulated, with mRNA levels of p53, ATM, and CHK2 being lower in patients with COVID-19. Several key p53 target genes involved in cell cycle arrest, apoptosis, and p53 feedback inhibition were upregulated in patients with COVID-19 while other p53 target genes were downregulated. This dysregulation has functional consequences as the transcription of p53-dependant genes (CCNG1, GADD45A, DDB2, SESN1, FDXR, APOBEC) was reduced 24 hours after x-ray exposure ex vivo to both low (100 mGy) or high (2 Gy) doses.Conclusions: SARS-CoV-2 infection affects a DNA damage response that may modify radiation-induced health risks in exposed patients with COVID-19

Deficient Radiation Transcription Response in COVID-19 Patients

Purpose: The ongoing SARS-CoV-2 pandemic has resulted in over 6.3 million deaths and 560 million COVID-19 cases worldwide. Clinical management of hospitalized patients is complex due to the heterogeneous course of COVID-19. Low-dose radiation therapy is known to dampen localized chronic inflammation and has been suggested to be used to reduce lung inflammation in patients with COVID-19. However, it is unknown whether SARS-CoV-2 alters the radiation response and associated radiation exposure related risk.Methods and Materials: We generated gene expression profiles from circulating leukocytes of hospitalized patients with COVID-19 and healthy donors.Results: The p53 signaling pathway was found to be dysregulated, with mRNA levels of p53, ATM, and CHK2 being lower in patients with COVID-19. Several key p53 target genes involved in cell cycle arrest, apoptosis, and p53 feedback inhibition were upregulated in patients with COVID-19 while other p53 target genes were downregulated. This dysregulation has functional consequences as the transcription of p53-dependant genes (CCNG1, GADD45A, DDB2, SESN1, FDXR, APOBEC) was reduced 24 hours after x-ray exposure ex vivo to both low (100 mGy) or high (2 Gy) doses.Conclusions: SARS-CoV-2 infection affects a DNA damage response that may modify radiation-induced health risks in exposed patients with COVID-19

Mesenchymal stromal cell therapy compared to SGLT2-inhibitors and usual care in treating diabetic kidney disease: A cost-effectiveness analysis

BACKGROUND AND OBJECTIVES: To simulate the cost-effectiveness of Mesenchymal Stromal Cell (MSC) therapy compared to sodium/glucose co-transporter 2 inhibitors (SGLT2i) or usual care (UC) in treating patients with Diabetic Kidney Disease (DKD). DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: This Markov-chain Monte Carlo model adopted a societal perspective and simulated 10,000 patients with DKD eligible for MSC therapy alongside UC using a lifetime horizon. This cohort was compared with an SGLT2i alongside UC arm and a UC only arm. Model input data were extracted from the literature. A threshold of $47,000 per quality-adjusted life year and a discount rate of 3$4,158 and -$10,085 respectively indicating that SGLT2i, MSC and UC had a 64%, 34% and 1% probability of being cost-effective at the given threshold, respectively. This pattern was consistent across most scenarios; driven by the relatively low cost of SGLT2i and demonstrated class-effect in delaying kidney failure and all-cause mortality. When examining younger patients at baseline, SGLT2i was still the most cost-effective but MSC performed better against UC given the increased lifetime benefit from delaying progression to ESRD. CONCLUSIONS: The evidence base regarding the effectiveness of MSC therapy continues to evolve. The potential for these therapies to reverse kidney damage would see large improvements in their cost-effectiveness as would targeting such therapies at younger patients and/or those for whom SGLT2i is contra-indicated