Identifying factors that promote and limit the effective use of real-time patient experience feedback: a mixed-methods study in secondary care

Objectives: The Friends and Family Test (FFT) is commissioned by the National Health Service (NHS) in England to capture patient experience as a real-time feedback initiative for patient-centred quality improvement (QI). The aim of this study was to create a process map in order to identify the factors that promote and limit the effective use of FFT as a real-time feedback initiative for patient-centred QI. Setting: This study was conducted at a large London NHS Trust. Services include accident and emergency, inpatient, outpatient and maternity, which routinely collect FFT patient experience data. Participants: Healthcare staff and key stakeholders involved in FFT. Interventions: Semi-structured interviews were conducted on fifteen participants from a broad range of professional groups to evaluate their engagement with the FFT. Interview data were recorded, transcribed, and analysed for using deductive thematic analysis. Results: Concerns related to inefficiency in the flow of FFT data, lack of time to analyse FFT reports (with emphasis on high level reporting rather than QI), insufficient access to FFT reports and limited training provided to understand FFT reports for frontline staff. The sheer volume of data received was not amenable to manual thematic analysis resulting in inability to acquire insight from the free-text. This resulted in staff ambivalence towards FFT as a near real-time feedback initiative. Conclusions: The results state that there is too much FFT free text for meaningful analysis, and the output is limited to the provision of sufficient capacity and resource to analyse the data, without consideration of other options, such as text analytics and amending the data collection tool

Use and impact of virtual primary care on quality and safety: The public's perspectives during the COVID-19 pandemic

Introduction With the onset of Coronavirus disease (COVID-19), primary care has swiftly transitioned from face-to-face to virtual care, yet it remains largely unknown how this has impacted the quality and safety of care. We aim to evaluate patient use of virtual primary care models during COVID-19, including change in uptake, perceived impact on the quality and safety of care and willingness of future use. Methodology An online cross-sectional survey was administered to the public across the United Kingdom, Sweden, Italy and Germany. McNemar tests were conducted to test pre- and post-pandemic differences in uptake for each technology. One-way analysis of variance was conducted to examine patient experience ratings and perceived impacts on healthcare quality and safety across demographic characteristics. Results Respondents (n = 6326) reported an increased use of telephone consultations ( + 6.3%, p < .001), patient-initiated services ( + 1.5%, n = 98, p < 0.001), video consultations ( + 1.4%, p < .001), remote triage ( + 1.3, p < 0.001) and secure messaging systems ( + 0.9%, p = .019). Experience rates using virtual care technologies were higher for men (2.4  ±  1.0 vs. 2.3  ±  0.9, p < .001), those with higher literacy (2.8  ±  1.0 vs. 2.3  ±  0.9, p < .001), and participants from Germany (2.5  ±  0.9, p < .001). Healthcare timeliness and efficiency were the dimensions most often reported as being positively impacted by virtual technologies (60.2%, n = 2793 and 55.7%, n = 2,401, respectively), followed by effectiveness (46.5%, n = 1802), safety (45.5%, n = 1822), patient-centredness (45.2%, n = 45.2) and equity (42.9%, n = 1726). Interest in future use was highest for telephone consultations (55.9%), patient-initiated digital services (56.1%), secure messaging systems (43.4%), online triage (35.1%), video consultations (37.0%) and chat consultations (30.1%), although significant variation was observed between countries and patient characteristics. Discussion Future work must examine the drivers and determinants of positive experiences using remote care to co-create a supportive environment that ensures equitable adoption and use. Comparative analysis between countries and health systems offers the opportunity for policymakers to learn from best practices internationally

ATAD5 promotes replication restart by regulating RAD51 and PCNA in response to replication stress

Maintaining stability of replication forks is important for genomic integrity. However, it is not clear how replisome proteins contribute to fork stability under replication stress. Here, we report that ATAD5, a PCNA unloader, plays multiple functions at stalled forks including promoting its restart. ATAD5 depletion increases genomic instability upon hydroxyurea treatment in cultured cells and mice. ATAD5 recruits RAD51 to stalled forks in an ATR kinase-dependent manner by hydroxyurea-enhanced protein-protein interactions and timely removes PCNA from stalled forks for RAD51 recruitment. Consistent with the role of RAD51 in fork regression, ATAD5 depletion inhibits slowdown of fork progression and native 5-bromo-2??-deoxyuridine signal induced by hydroxyurea. Single-molecule FRET showed that PCNA itself acts as a mechanical barrier to fork regression. Consequently, DNA breaks required for fork restart are reduced by ATAD5 depletion. Collectively, our results suggest an important role of ATAD5 in maintaining genome integrity during replication stress

Disruption of mouse Slx4, a regulator of structure-specific nucleases, phenocopies Fanconi anemia

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Mammalian BTBD12 (SLX4) Protects against Genomic Instability during Mammalian Spermatogenesis

The mammalian ortholog of yeast Slx4, BTBD12, is an ATM substrate that functions as a scaffold for various DNA repair activities. Mutations of human BTBD12 have been reported in a new sub-type of Fanconi anemia patients. Recent studies have implicated the fly and worm orthologs, MUS312 and HIM-18, in the regulation of meiotic crossovers arising from double-strand break (DSB) initiating events and also in genome stability prior to meiosis. Using a Btbd12 mutant mouse, we analyzed the role of BTBD12 in mammalian gametogenesis. BTBD12 localizes to pre-meiotic spermatogonia and to meiotic spermatocytes in wildtype males. Btbd12 mutant mice have less than 15% normal spermatozoa and are subfertile. Loss of BTBD12 during embryogenesis results in impaired primordial germ cell proliferation and increased apoptosis, which reduces the spermatogonial pool in the early postnatal testis. During prophase I, DSBs initiate normally in Btbd12 mutant animals. However, DSB repair is delayed or impeded, resulting in persistent γH2AX and RAD51, and the choice of repair pathway may be altered, resulting in elevated MLH1/MLH3 focus numbers at pachynema. The result is an increase in apoptosis through prophase I and beyond. Unlike yeast Slx4, therefore, BTBD12 appears to function in meiotic prophase I, possibly during the recombination events that lead to the production of crossovers. In line with its expected regulation by ATM kinase, BTBD12 protein is reduced in the testis of Atm−/− males, and Btbd12 mutant mice exhibit increased genomic instability in the form of elevated blood cell micronucleus formation similar to that seen in Atm−/− males. Taken together, these data indicate that BTBD12 functions throughout gametogenesis to maintain genome stability, possibly by co-ordinating repair processes and/or by linking DNA repair events to the cell cycle via ATM

Msh2 Blocks an Alternative Mechanism for Non-Homologous Tail Removal during Single-Strand Annealing in Saccharomyces cerevisiae

Chromosomal translocations are frequently observed in cells exposed to agents that cause DNA double-strand breaks (DSBs), such as ionizing radiation and chemotherapeutic drugs, and are often associated with tumors in mammals. Recently, translocation formation in the budding yeast, Saccharomyces cerevisiae, has been found to occur at high frequencies following the creation of multiple DSBs adjacent to repetitive sequences on non-homologous chromosomes. The genetic control of translocation formation and the chromosome complements of the clones that contain translocations suggest that translocation formation occurs by single-strand annealing (SSA). Among the factors important for translocation formation by SSA is the central mismatch repair (MMR) and homologous recombination (HR) factor, Msh2. Here we describe the effects of several msh2 missense mutations on translocation formation that suggest that Msh2 has separable functions in stabilizing annealed single strands, and removing non-homologous sequences from their ends. Additionally, interactions between the msh2 alleles and a null allele of RAD1, which encodes a subunit of a nuclease critical for the removal of non-homologous tails suggest that Msh2 blocks an alternative mechanism for removing these sequences. These results suggest that Msh2 plays multiple roles in the formation of chromosomal translocations following acute levels of DNA damage

Determinants of burnout and other aspects of psychological well-being in healthcare workers during the Covid-19 pandemic: A multinational cross-sectional study

The Covid-19 pandemic has placed unprecedented pressure on healthcare systems and workers around the world. Such pressures may impact on working conditions, psychological wellbeing and perception of safety. In spite of this, no study has assessed the relationship between safety attitudes and psychological outcomes. Moreover, only limited studies have examined the relationship between personal characteristics and psychological outcomes during Covid-19. From 22nd March 2020 to 18th June 2020, healthcare workers from the United Kingdom, Poland, and Singapore were invited to participate using a self-administered questionnaire comprising the Safety Attitudes Questionnaire (SAQ), Oldenburg Burnout Inventory (OLBI) and Hospital Anxiety and Depression Scale (HADS) to evaluate safety culture, burnout and anxiety/depression. Multivariate logistic regression was used to determine predictors of burnout, anxiety and depression. Of 3,537 healthcare workers who participated in the study, 2,364 (67%) screened positive for burnout, 701 (20%) for anxiety, and 389 (11%) for depression. Significant predictors of burnout included patient-facing roles: doctor (OR 2.10; 95% CI 1.49–2.95), nurse (OR 1.38; 95% CI 1.04–1.84), and ‘other clinical’ (OR 2.02; 95% CI 1.45–2.82); being redeployed (OR 1.27; 95% CI 1.02–1.58), bottom quartile SAQ score (OR 2.43; 95% CI 1.98–2.99), anxiety (OR 4.87; 95% CI 3.92–6.06) and depression (OR 4.06; 95% CI 3.04–5.42). Significant factors inversely correlated with burnout included being tested for SARS-CoV-2 (OR 0.64; 95% CI 0.51–0.82) and top quartile SAQ score (OR 0.30; 95% CI 0.22–0.40). Significant factors associated with anxiety and depression, included burnout, gender, safety attitudes and job role. Our findings demonstrate a significant burden of burnout, anxiety, and depression amongst healthcare workers. A strong association was seen between SARS-CoV-2 testing, safety attitudes, gender, job role, redeployment and psychological state. These findings highlight the importance of targeted support services for at risk groups and proactive SARS-CoV-2 testing of healthcare workers

Caenorhabditis elegans HIM-18/SLX-4 Interacts with SLX-1 and XPF-1 and Maintains Genomic Integrity in the Germline by Processing Recombination Intermediates

Homologous recombination (HR) is essential for the repair of blocked or collapsed replication forks and for the production of crossovers between homologs that promote accurate meiotic chromosome segregation. Here, we identify HIM-18, an ortholog of MUS312/Slx4, as a critical player required in vivo for processing late HR intermediates in Caenorhabditis elegans. DNA damage sensitivity and an accumulation of HR intermediates (RAD-51 foci) during premeiotic entry suggest that HIM-18 is required for HR–mediated repair at stalled replication forks. A reduction in crossover recombination frequencies—accompanied by an increase in HR intermediates during meiosis, germ cell apoptosis, unstable bivalent attachments, and subsequent chromosome nondisjunction—support a role for HIM-18 in converting HR intermediates into crossover products. Such a role is suggested by physical interaction of HIM-18 with the nucleases SLX-1 and XPF-1 and by the synthetic lethality of him-18 with him-6, the C. elegans BLM homolog. We propose that HIM-18 facilitates processing of HR intermediates resulting from replication fork collapse and programmed meiotic DSBs in the C. elegans germline

Processing of joint molecule intermediates by structure-selective endonucleases during homologous recombination in eukaryotes

Homologous recombination is required for maintaining genomic integrity by functioning in high-fidelity repair of DNA double-strand breaks and other complex lesions, replication fork support, and meiotic chromosome segregation. Joint DNA molecules are key intermediates in recombination and their differential processing determines whether the genetic outcome is a crossover or non-crossover event. The Holliday model of recombination highlights the resolution of four-way DNA joint molecules, termed Holliday junctions, and the bacterial Holliday junction resolvase RuvC set the paradigm for the mechanism of crossover formation. In eukaryotes, much effort has been invested in identifying the eukaryotic equivalent of bacterial RuvC, leading to the discovery of a number of DNA endonucleases, including Mus81–Mms4/EME1, Slx1–Slx4/BTBD12/MUS312, XPF–ERCC1, and Yen1/GEN1. These nucleases exert different selectivity for various DNA joint molecules, including Holliday junctions. Their mutant phenotypes and distinct species-specific characteristics expose a surprisingly complex system of joint molecule processing. In an attempt to reconcile the biochemical and genetic data, we propose that nicked junctions constitute important in vivo recombination intermediates whose processing determines the efficiency and outcome (crossover/non-crossover) of homologous recombination