Explore the vast range of titles available.

There is little evidence to support the case for yet more structural change

Health secretary Jeremy Hunt’s claims of savings of £1bn or £1.5bn a year seem unlikely

Sepsis is the overwhelming immunological response to infection, which if not treated can lead to multi-organ failure, shock and death. Specifically, neonatal sepsis results in 225,000 neonatal deaths globally per annum. Moreover, Uganda experiences one of the highest materno-fetal death rates (62,000 p.a.), with neonatal sepsis deaths at approximately 6,500 p.a.. The difficulty in diagnosing neonatal sepsis lies in the non-specific signs and symptoms associated with sepsis and an absence of definitive sepsis-specific biomarkers. However, serum amyloid A (SAA) detection has potential as a superior biomarker for the diagnosis of probable neonatal sepsis. Herein, in ethically-approved studies we have deployed a competitive lateral flow test (NeoSep-SAA (research-use only)) to detect SAA in whole blood at patient bedside in a resource-limited environment. Results are available within 10 minutes and test format is compatible with small blood volumes available from neonates (5 μl). NeoSep-SAA exhibited a high sensitivity and specificity for diagnosis of adult sepsis, and in neonates showed a sensitivity and specificity of 92% (89%, 95%) and 73% (68%, 77%) with PPV and NPV of 78% (75%, 81%) and 90% (86%, 93%), respectively (n = 714 individuals; 95% CI). NeoSep-SAA showed superior sensitivity for neonatal sepsis over C-Reactive Protein detection (sensitivity: 37%), albeit with some sacrifice of specificity. NeoSep-SAA enabled rapid diagnosis, which combined with minimally-invasive blood withdrawal, was less stressful for neonates. Overall, NeoSep-SAA can readily identify infection/inflammation and has the potential to enable rapid and informed clinical decisions to combat sepsis. This approach has potential to improve neonatal sepsis detection and reduce neonatal mortality in line with United Nations Sustainable Development Goal (SDG) 3.2 objectives.

Even at this late stage, the government would be wise to withdraw the bill

C-reactive protein (CRP), haptoglobin (Hp) and fibrinogen (Fbgn) are acute phase reactants (APRs), the blood levels of which increase during acute inflammation. However, although the levels of these APRs are used to monitor inflammation in man, their usefulness and sensitivity as markers of inflammation in rodents are less clear. We therefore wished to evaluate, in a comparative fashion, a prototype immunoassay for serum CRP, a commercial assay for serum Hp, and an automated assay for Fbgn, using a model of acute inflammation in the rat. Additionally, pro-inflammatory cytokines and serum protein fractions were also measured. The model of inflammation used was the intraperitoneal injection of Freund's complete adjuvant (FCA). In a concluding experiment, findings with Hp in the FCA rat model were validated in a toxicologically relevant study involving the induction of acute hepatic inflammation using the model hepatotoxicant carbon tetrachloride (CCl(4)). Female Wistar Han rats were treated with a single injection of FCA in a dose-response study (1.25-10.0 ml/kg, sampling at 36 h) and two time-course studies (over 40 h and 21 days). In a final experiment, rats were dosed with CCl(4) at 0.8 ml/kg and sampled over a 17-day period. In FCA and CCl(4) experiments, serum/plasma was prepared and tissues taken at autopsy for histological assessment (CCl(4) study only). In the dose-response study, serum CRP, Hp and plasma Fbgn were increased at all FCA dose levels at 36 h post-dosing. Serum alpha(2) and beta(1) globulin fractions were also increased, while albumin levels were decreased. In the 40-h time-course study, CRP levels peaked at 25-40 h post-dosing, to approximately 120% of control (as 100%). Hp levels increased to a maximum at 25 and 40 h post-dosing with values greater than 400% of control, and alpha(2) and beta(1) globulin fractions peaked at 30 and 40 h post-dosing to 221 and 187% of control, respectively. Increased serum interleukin-6 (IL-6) and interleukin-1beta (IL-1beta) levels peaked at 20 h (11-fold) and 25 h (19-fold), respectively. In a 21-day time-course study, no increased CRP levels were measured despite elevated levels of Hp, which peaked at 36 h (approximately 7-fold above control), and remained elevated up to 21 days. IL-6 and IL-1beta levels peaked at 12 h (19-fold) and 24 h (28-fold), respectively. Liver histopathology of animals treated with CCl(4) showed centrilobular hepatocellular degeneration and necrosis (most significant at 36 h) with an inflammatory response (most significant at 48 h). Resolution of the lesion was complete by 4 days post-dosing. Serum alanine aminotransferase, aspartate aminotransferase and glutamate dehydrogenase levels peaked at 36 h post-dosing. Hp levels increased maximally at 48 h (426% of control). We conclude that serum CRP is a poor marker of acute inflammation in the rat in comparison with serum Hp and plasma Fbgn. Between Hp and Fbgn, serum Hp is shown to be the most sensitive and useful marker of acute inflammation.

[...]few people would argue with the principle that health policy should be evidence based-it should make full and proper use of research findings and research methods in policy development, implementation, and evaluation.