Multimorbidity and health-related quality of life (HRQoL) in a nationally representative population sample: implications of count versus cluster method for defining multimorbidity on HRQoL

Background: No universally accepted definition of multimorbidity (MM) exists, and implications of different definitions have not been explored. This study examined the performance of the count and cluster definitions of multimorbidity on the sociodemographic profile and health-related quality of life (HRQoL) in a general population. Methods: Data were derived from the nationally representative 2007 Australian National Survey of Mental Health and Wellbeing (n = 8841). The HRQoL scores were measured using the Assessment of Quality of Life (AQoL-4D) instrument. The simple count (2+ & 3+ conditions) and hierarchical cluster methods were used to define/identify clusters of multimorbidity. Linear regression was used to assess the associations between HRQoL and multimorbidity as defined by the different methods. Results: The assessment of multimorbidity, which was defined using the count method, resulting in the prevalence of 26% (MM2+) and 10.1% (MM3+). Statistically significant clusters identified through hierarchical cluster analysis included heart or circulatory conditions (CVD)/arthritis (cluster-1, 9%) and major depressive disorder (MDD)/anxiety (cluster-2, 4%). A sensitivity analysis suggested that the stability of the clusters resulted from hierarchical clustering. The sociodemographic profiles were similar between MM2+, MM3+ and cluster-1, but were different from cluster-2. HRQoL was negatively associated with MM2+ (β: −0.18, SE: −0.01, p < 0.001), MM3+ (β: −0.23, SE: −0.02, p < 0.001), cluster-1 (β: −0.10, SE: 0.01, p < 0.001) and cluster-2 (β: −0.36, SE: 0.01, p < 0.001). Conclusions: Our findings confirm the existence of an inverse relationship between multimorbidity and HRQoL in the Australian population and indicate that the hierarchical clustering approach is validated when the outcome of interest is HRQoL from this head-to-head comparison. Moreover, a simple count fails to identify if there are specific conditions of interest that are driving poorer HRQoL. Researchers should exercise caution when selecting a definition of multimorbidity because it may significantly influence the study outcomes

The experiences and perceptions of wellbeing provision among English ambulance services staff: a multi-method qualitative study

Background: NHS ambulance service staff are at risk of poor physical and mental wellbeing because of the likelihood of encountering stressful and traumatic incidents. While reducing sickness absence and improving wellbeing support to ambulance staff is a key NHS priority, few studies have empirically documented a national picture to inform policy and service re-design. The study aimed to understand how ambulance service trusts in England deal with staff health and wellbeing, as well as how the staff perceive and use wellbeing services. Methods: To achieve our aim, we undertook semi-structured telephone interviews with health and wellbeing leads and patient-facing ambulance staff, as well as undertaking documentary analysis of ambulance trust policies on wellbeing. The study was conducted both before and during the UK first COVID-19 pandemic wave. The University of Lincoln ethics committee and the Health Research Authority (HRA) granted ethical approval. Overall, we analysed 57 staff wellbeing policy documents across all Trusts. Additionally, we interviewed a Health and Wellbeing Lead in eight Trusts as well as 25 ambulance and control room staff across three Trusts. Results: The study highlighted clear variations between organisational and individual actions to support wellbeing across Trust policies. Wellbeing leads acknowledged real ‘tensions’ between individual and organisational responsibility for wellbeing. Behaviour changes around diet and exercise were perceived to have a positive effect on the overall mental health of their workforce. Wellbeing leads generally agreed that mental health was given primacy over other wellbeing initiatives. Variable experiences of health and wellbeing support were partly contingent on the levels of management support, impacted by organisational culture and service delivery challenges for staff. Conclusion: Ambulance service work can impact upon physical and mental health, which necessitates effective support for staff mental health and wellbeing. Increasing the knowledge of line managers around the availability of services could improve engagement

Phage Orf family recombinases:conservation of activities and involvement of the central channel in DNA binding

Genetic and biochemical evidence suggests that λ Orf is a recombination mediator, promoting nucleation of either bacterial RecA or phage Redβ recombinases onto single-stranded DNA (ssDNA) bound by SSB protein. We have identified a diverse family of Orf proteins that includes representatives implicated in DNA base flipping and those fused to an HNH endonuclease domain. To confirm a functional relationship with the Orf family, a distantly-related homolog, YbcN, from Escherichia coli cryptic prophage DLP12 was purified and characterized. As with its λ relative, YbcN showed a preference for binding ssDNA over duplex. Neither Orf nor YbcN displayed a significant preference for duplex DNA containing mismatches or 1-3 nucleotide bulges. YbcN also bound E. coli SSB, although unlike Orf, it failed to associate with an SSB mutant lacking the flexible C-terminal tail involved in coordinating heterologous protein-protein interactions. Residues conserved in the Orf family that flank the central cavity in the λ Orf crystal structure were targeted for mutagenesis to help determine the mode of DNA binding. Several of these mutant proteins showed significant defects in DNA binding consistent with the central aperture being important for substrate recognition. The widespread conservation of Orf-like proteins highlights the importance of targeting SSB coated ssDNA during lambdoid phage recombination

Trigger for group A streptococcal M1T1 invasive disease

The globally disseminated Streptococcus pyogenes M1T1 clone causes a number of highly invasive human diseases. The transition from local to systemic infection occurs by an unknown mechanism; however invasive M1T1 clinical isolates are known to express significantly less cysteine protease SpeB than M1T1 isolates from local infections. Here, we show that in comparison to the M1T1 strain 5448, the isogenic mutant ΔspeB accumulated 75‐fold more human plasmin activity on the bacterial surface following incubation in human plasma. Human plasminogen was an absolute requirement for M1T1 strain 5448 virulence following subcutaneous (s.c.) infection of humanized plasminogen transgenic mice. S. pyogenes M1T1 isolates from the blood of infected humanized plasminogen transgenic mice expressed reduced levels of SpeB in comparison with the parental 5448 used as inoculum. We propose that the human plasminogen system plays a critical role in group A streptococcal M1T1 systemic disease initiation. SpeB is required for S. pyogenes M1T1 survival at the site of local infection, however, SpeB also disrupts the interaction of S. pyogenes M1T1 with the human plasminogen activation system. Loss of SpeB activity in a subpopulation of S. pyogenes M1T1 at the site of infection results in accumulation of surface plasmin activity thus triggering systemic spread.—Cole, J. N., McArthur, J. D., McKay, F. C., Sanderson‐Smith, M. L., Cork, A. J., Ranson, M., Rohde, M., Itzek, A., Sun, H., Ginsburg, D., Kotb, M., Nizet, V., Chhatwal, G. S., Walker, M. J. Trigger for group A streptococcal M1T1 invasive disease. FASEB J. 20, E1139–E1145 (2006)Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154248/1/fsb2fj065804fje.pd

Are We Capturing Faunal Intactness? A Comparison of Intact Forest Landscapes and the “Last of the Wild in Each Ecoregion”

Efforts to designate priority areas for conservation have had a long history, with most modern initiatives focused on either designating areas important for biodiversity or those least impacted by direct human disturbance. Ecologically intact ecosystems are becoming increasingly limited on the planet, making their identification and conservation an important priority. Intact forest landscapes (IFL) are defined as forests that are mainly free of significant anthropogenic degradation and at least 500 km2 in size. Here we define a new metric, the Last of the Wild in each Ecoregion (LWE), as a preliminary scoping of the most intact parts of each ecoregion. IFL and LWE are approaches among a broad family of techniques to mapping ecological integrity at the global scale. Although both implicitly include species integrity as a dimension of intactness, this is inferred rather than directly measured. We assessed whether IFL or LWE areas were better at capturing species where they are most abundant using species distribution data for a set of forest species for which range-wide data were available and human activity limits the range. We found that IFL and LWE methods identified areas where species we assessed are either absent or at too low an abundance to be ecologically functional. As such many IFL/LWE polygons did not have intact fauna. We also show that 54.7% of the terrestrial realm (excluding Antarctica) has at least one species recorded as extinct and that two thirds of IFL/LWE areas overlap with areas where species have gone extinct in the past 500 years. The results show that even within the most remote areas, serious faunal loss has taken place at many localities so direct species survey work is also needed to confirm faunal intactness

Reliability and sensitivity to change of the bristol rheumatoid arthritis fatigue scales

Objective. To examine the reliability (stability) and sensitivity of the Bristol Rheumatoid Arthritis Fatigue scales (BRAFs) and patient-reported outcome measures (PROMs) developed to capture the fatigue experience. The Multi-Dimensional Questionnaire (BRAF-MDQ) has a global score and four subscales (Physical Fatigue, Living with Fatigue, Cognitive Fatigue and Emotional Fatigue), while three numerical rating scales (BRAF-NRS) measure fatigue Severity, Effect and Coping. Methods. RA patients completed the BRAFs plus comparator PROMs. Reliability (study 1): 50 patients completed questionnaires twice. A same-day test-retest interval (minimum 60 min) ensured both time points related to the same 7 days, minimizing the capture of fatigue fluctuations. Reliability (study 2): 50 patients completed the same procedure with a re-worded BRAF-NRS Coping. Sensitivity to change (study 3): 42 patients being given clinically a single high dose of i.m. glucocorticoids completed questionnaires at weeks 0 and 2.Results. The BRAF-MDQ, its subscales and the BRAF-NRS showed very strong reliability (r = 0.82-0.95). BRAF-NRS Coping had lower moderate reliability in both wording formats (r = 0.62, 0.60). The BRAF-MDQ, its subscales and the BRAF-NRS Severity and Effect were sensitive to change, with effect sizes (ESs) of 0.33-0.56. As hypothesized, the BRF-NRS Coping was not responsive to the pharmaceutical intervention (ES 0.05). Preliminary exploration suggests a minimum clinically important difference of 17.5% for improvement and 6.1% for fatigue worsening. Conclusion. The BRAF scales show good reliability and sensitivity to change. The lack of BRAF-NRS Coping responsiveness to medication supports the theory that coping with fatigue is a concept distinct from severity and effect that is worth measuring separately. © The Author 2013. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved