Showing papers by "Wishaw General Hospital published in 2020"

Changes in Plasma Itaconate Elevation in Early Rheumatoid Arthritis Patients Elucidates Disease Activity Associated Macrophage Activation.

Abstract: Changes in the plasma metabolic profile were characterised in newly diagnosed rheumatoid arthritis (RA) patients upon commencement of conventional disease-modifying anti-rheumatic drug (cDMARD) therapy. Plasma samples collected in an early RA randomised strategy study (NCT00920478) that compared clinical (DAS) disease activity assessment with musculoskeletal ultrasound assessment (MSUS) to drive treatment decisions were subjected to untargeted metabolomic analysis. Metabolic profiles were collected at pre- and three months post-commencement of nonbiologic cDMARD. Metabolites that changed in association with changes in the DAS44 score were identified at the three-month timepoint. A total of nine metabolites exhibited a clear correlation with a reduction in DAS44 score following cDMARD commencement, particularly itaconate, its derived anhydride and a derivative of itaconate CoA. Increasing itaconate correlated with improved DAS44 score and decreasing levels of C-reactive protein (CRP). cDMARD treatment effects invoke consistent changes in plasma detectable metabolites, that in turn implicate clinical disease activity with macrophages. Such changes inform RA pathogenesis and reveal for the first time a link between itaconate production and resolution of inflammatory disease in humans. Quantitative metabolic biomarker-based tests of clinical change in state are feasible and should be developed around the itaconate pathway.

Impact of newborn screening on outcomes and social inequalities in cystic fibrosis: a UK CF registry-based study

Abstract: Background Newborn bloodspot screening (NBS) for cystic fibrosis (CF) was introduced across the UK in 2007 but the impact on clinical outcomes and health inequalities for children with CF is unclear. Methods We undertook longitudinal analyses of UK CF registry data on over 3000 children with CF born between 2000 and 2015. Clinical outcomes were the trajectories of percent predicted forced expiratory volume in one second (%FEV1) from age 5, weight for age and body mass index (BMI) SD-scores from age one, and time to chronic Pseudomonas aeruginosa (cPA) infection. Using mixed effects and time-to-event models we assessed the association of NBS with outcomes and potential interactions with childhood socioeconomic conditions, while adjusting for confounders. Results NBS was associated with higher average lung function trajectory (+1.56 FEV1 percentage points 95% CI 0.1 to 3.02, n=2216), delayed onset of cPA, and higher average weight trajectory intercept at age one (+0.16 SD; 95% CI 0.07 to 0.26, n=3267) but negative rate of weight change thereafter (−0.02 SD per year; 95% CI −0.03 to −0.00). We found no significant association of NBS with BMI or rate of change of lung function. There was no clear evidence of an impact of NBS on health inequalities early in life. Conclusions Children diagnosed with CF by NBS in the UK have better lung function and increased early weight but NBS does not appear to have narrowed early health inequalities.

Respiratory mechanics during initial lung aeration at birth in the preterm lamb.

Abstract: Despite recent insights into the dynamic processes during lung aeration at birth, several aspects remain poorly understood. We aimed to characterize changes in lung mechanics during the first inflation at birth and their relationship to changes in lung volume. Intubated preterm lambs (gestational age, 124-127 days; n = 17) were studied at birth. Lung volume changes were measured by electrical impedance tomography (VLEIT). Respiratory system resistance (R5) and oscillatory compliance (Cx5) were monitored with the forced oscillation technique at 5 Hz. Lambs received 3-7 s of 8 cmH2O of continuous distending pressure (CDP) before delivery of a sustained inflation (SI) of 40 cmH2O. The SI was then applied until either Cx5 or the VLEIT or the airway opening volume was stable. CDP was resumed for 3-7 s before commencement of mechanical ventilation. The exponential increases with time of Cx5 and VLEIT from commencement of the SI were characterized by estimating their time constants (τCx5 and τVLEIT, respectively). During SI, a fast decrease in R5 and an exponential increase in Cx5 and VLEIT were observed. Cx5 and VLEIT provided comparable information on the dynamics of lung aeration in all lambs, with τCx5 and τVLEIT being highly linearly correlated (r2 = 0.87, P < 0.001). Cx5 and VLEIT decreased immediately after SI. Despite the standardization of the animal model, changes in Cx5 and R5 both during and after SI were highly variable. Lung aeration at birth is characterized by a fast reduction in resistance and a slower increase in oscillatory compliance, the latter being a direct reflection of the amount of lung aeration.

Regulation of Advanced Critical Care Practitioners: Past, present and future:

Abstract: The role of Advanced Critical Care Practitioners was included in the Department of Health’s recent consultation document on the regulation of Medical Associate Professions. This prompted the author...

The 'apple core' cement spacer for the management of massive bone loss in two-stage revision knee arthroplasty for infection.

Abstract: Antibiotic-loaded cement spacers are used in two-stage revision knee arthroplasty for infection, but commercially available spacers may not always be suitable for significant bone loss or soft tissue failure in multiply revised cases. We describe a technique for producing an on-table, static, reinforced cement spacer – the ‘apple core’ spacer – with the intended outcome of providing joint stability in such patients, prior to undertaking a second-stage procedure. Following a radical debridement, the spacer is made of three components: (1) a ‘central bar’ of external fixator connecting rods, combined using cerclage wires as needed; (2) a standard polymethylmethacrylate cement ‘apple core’; and (3) a covering ‘skin’ of high dose antibiotic-loaded cement, which is stippled as it sets, to increase the surface area and facilitate antibiotic elution. This technique was performed in nine patients who underwent two-stage salvage revision for complex, recurrent infected total knee arthroplasty at a single institution. All patients successfully went on to definitive second-stage reimplantation and have retained their limbs. The ‘apple core’ cement spacer allows massive bone defects to be effectively managed between staged revision procedures.

Fear of Birth and Modern Maternity Systems of Care

Abstract: This chapter will examine the lived experience of maternity systems and how this shapes practice for obstetricians and midwives. In searching deeper into the care systems we will discover the way women present with anxiety and fear, how this is managed within maternity settings. Why recognising that pregnancy and birth leading to motherhood is more than a physiological event; the best care ensures that women’s psychological wellbeing is nurtured too. Who are these women and what can we learn from them in developing our services to support them. Using an example from a consultant midwife’s clinical setting some of these answers will be revealed.