Association between tocilizumab treatment of hyperinflammatory patients with COVID-19 in a critical care setting and elevated incidence of hospital-acquired bacterial and invasive fungal infections.

BACKGROUND: Tocilizumab is an interleukin-6 inhibitor that reduces mortality and the need for invasive mechanical ventilation, while increasing the possibility of successful hospital discharge for hyperinflammatory patients with severe coronavirus disease 2019 (COVID-19). No increase in adverse events or serious infections has been reported previously. AIM: To describe the characteristics and outcomes of patients with severe COVID-19 in critical care who received tocilizumab, and to compare mortality and length of hospital stay for patients who received tocilizumab (N=41) with those who did not (N=33). METHODS: Retrospective review of data related to patients with COVID-19 who received tocilizumab in a critical care setting from 1st January to 31st December 2021. FINDINGS: Amongst COVID-19 survivors, those who had received tocilizumab had longer intensive care unit (ICU) stays (median length 21 vs 9 days) and hospital stays (45 vs 34 days) compared with those who had not received tocilizumab. Thirty-day mortality (29% vs 36%; P=0.5196) and 60-day mortality (37% and 42%; P=0.6138) were not significantly lower in patients who received tocilizumab. Serious bacterial and fungal infections occurred at higher frequency amongst patients who received tocilizumab [odds ratio (OR) 2.67, 95% confidence interval (CI) 1.04-6.86; P=0.042], and at significantly higher frequency than in non-COVID-19 ICU admissions (OR 5.26, 95% CI 3.08-9.00; P<0.0001). CONCLUSIONS: In this single-centre study, patients in critical care with severe COVID-19 who received tocilizumab had a greater number of serious bacterial and fungal infections, but this may not have been a direct effect of tocilizumab treatment.

Six-month outcomes from living well with diabetes: A randomized trial of a telephone-delivered weight loss and physical activity intervention to improve glycemic control.

BACKGROUND: Intensive lifestyle intervention trials in type 2 diabetes contribute evidence on what can be achieved under optimal conditions, but are less informative for translation in applied settings. PURPOSE: Living Well with Diabetes is a telephone-delivered weight loss intervention designed for real-world delivery. METHODS: This study is a randomized controlled trial of telephone counseling (n = 151) versus usual care (n = 151); 6-month primary outcomes of weight, physical activity, HbA1c; secondary diet outcomes; analysis was by adjusted generalized linear models. RESULTS: Relative to usual care, telephone counseling participants had small but significantly better weight loss [-1.12 % of initial body weight; 95 % confidence interval (CI) -1.92, -0.33 %]; physical activity [relative rate (RR) = 1.30; 95 % CI, 1.08, 1.57]; energy intake reduction (-0.63 MJ/day; 95 % CI, -1.01, -0.25); and diet quality (3.72 points; 95 % CI, 1.77, 5.68), with no intervention effect for HbA1c (RR = 0.99; 95 % CI, 0.96, 1.01). CONCLUSIONS: Results are discussed in light of challenges to intervention delivery.

Aging impact on brain biomechanics with applications to hydrocephalus.

Hydrocephalus is a neurological disorder whose clinical symptoms and treatment outcome are correlated with patient age. In Wilkie et al. (2010, A theoretical study of the effect of intraventricular pulsations on the pathogenesis of hydrocephalus. Appl. Math. Comput., 215, 3181-3191), the fractional Zener model was used to investigate the role of cerebrospinal fluid pressure pulsations in the development of hydrocephalus in infants and adults. In this paper, we determine the mechanical parameters of the fractional Zener model for the infant and adult brains using age-dependent shear complex modulus data (Thibault, K. L. & Margulies, S. S. (1998) Age-dependent material properties of the porcine cerebrum: effect on pediatric inertial head injury criteria. J. Biomech., 31, 1119-1126). The displacement of brain tissue under conditions representing the onset of hydrocephalus are then calculated. The infant brain was found to produce tissue displacements that are unphysical for our model geometry and a new boundary condition is proposed to replace the stress-free outer boundary condition used in Wilkie et al. (2010). The steadystate elastic modulus is identified as the parameter of interest in the development of hydrocephalus: it is found to increase from the infant value of 621 Pa to the young adult value of 955 Pa and we hypothesize that it then decreases with age. The low steady-state elastic modulus of the infant brain (and possibly the aged brain) increases the tissue's susceptibility to large deformations and thus to the ventricular expansion characteristic of hydrocephalus.

'After the stroke': patients' and carers' experiences of healthcare after stroke in Scotland.

We report findings on patients with stroke and carers experiences of the healthcare system in Scotland after stroke. These findings emerged from data collected in a primary qualitative study exploring patients with stroke and carers perception of a Functional Electrical Stimulation (FES) Clinic. Rich data emerged in relation to healthcare after stroke as experienced by both patients and carers, highlighting important clinically relevant messages and constituting an important area for dissemination. Thirteen patients with stroke and nine carers consented to participate. Data were collected using face-to-face semi-structured interviews, undertaken in April and May 2007, and analysed using the framework of Interpretative Phenomenological Analysis (IPA). IPA aims to explore in depth the participants lived experiences of a specific phenomenon. An overarching theme of 'After the stroke' was identified. Within this, six sub-themes emerged entitled, (1) 'What is wrong?'; (2) 'Help came quickly'; (3) 'Something is still wrong'; (4) 'In the hospital'; (5) 'I'm taking them home' and (6) 'Back at home'. Interestingly, patients with stroke and carers recalled similar parts of the pathway through the healthcare system after stroke, resulting in the six chronological sub-themes. The data highlighted issues surrounding recognition of stroke symptoms by both participants and professionals; expeditious admission to hospital and stroke unit; consultation during the discharge planning process and access to support and community follow up. Despite the availability of clinical guidelines to direct the management of stroke, this study suggests that the experiences of patients with stroke and carers do not always concur with guideline recommendations. These results highlight that such recommendations do not always transfer into clinical practice. Both clinicians and service managers should consider these issues when delivering care to patients after stroke.

The iron uptake mechanisms of enteropathogenic Escherichia coli: the use of haem and haemoglobin during growth in an iron-limited environment.

The iron uptake mechanisms of enteropathogenic Escherichia coli (EPEC) were examined and compared with those of control E. coli strains. The incidence of aerobactin production was similar (39% and 37% respectively) in the two groups. The quantities of enterochelin produced by aerobactin-negative EPEC and control strains were similar, as were the quantities of enterochelin produced by aerobactin-positive EPEC and control strains. The ability to use haem or haemoglobin as an iron source in an iron-restricted environment was found in 80.4% and 60.8% of EPEC strains respectively, and in 76.6% and 56.6% of control E. coli strains. The ability of E. coli strains to use these compounds was not related to the production of enterochelin or aerobactin or to the production of haemolysins, and may be an important characteristic of bowel organisms. When growing in an iron-limited environment, the iron contained in haemoglobin was used in preference to ovotransferrin-bound iron. During periods of haemoglobin-stimulated growth, the enterochelin uptake system was shown to be fully expressed and may be involved in transport of haemoglobin-derived iron into the cell. Uptake of ovotransferrin-bound iron took place immediately upon exhaustion of haemoglobin-derived iron. The ability to use iron derived from haem compounds represents an alternative iron uptake mechanism for organisms growing in an iron-limited environment and allows greater flexibility during growth in vivo.

The polysaccharides of agricultural lupin seeds.

The polysaccharides of the seeds of four species of agricultural lupin have been shown to comprise galactans, arabinogalactans, arabinans, rhamnogalacturonans, and galactoxyloglucans. Low molecular weight compounds were present in the mixtures after methylation of the acidic polysaccharides. Three tri-O-acetyl-O-methylhexuronic acids, with one hydroxyl group unsubstituted, formed during methylation, hydrolysis, and acetylation of the acidic polysaccharides, were present in high and variable proportions.

Examination of enteropathogenic Escherichia coli strains for an adenylcyclase stimulating factor.

Enteropathogenic Escherichia coli strains are a common cause of infantile diarrhoea but do not produce recognised enterotoxins. Three strains of proven virulence were examined for toxins which may be missed in conventional tests. Cell lysates and concentrated culture supernates of organisms grown in five different media gave negative results when examined for adenylcyclase stimulating activity. The additions of zinc ions or lincomycin to these media or the use of iron-depleted media also gave negative results. The significance of these findings and the possible role of other toxins in diarrhoea due to enteropathogenic E. coli are discussed.