Potential impact of national recommendations to use short course antibiotic therapy on antibiotic use in the emergency department of a UK hospital: retrospective observational study.

BACKGROUND AND IMPORTANCE: The National Institute for Health and Care Excellence (NICE) antimicrobial prescribing guidelines for common infections recommend short course antimicrobial therapy in order to reduce antibiotic associated harm. OBJECTIVE: To quantify the opportunity to reduce antibiotic use in an emergency department (ED) through adoption of these short antibiotic course recommendations. DESIGN, SETTINGS AND PARTICIPANTS: A retrospective observational study in an ED in the UK with 95 000 attendances a year. Patients managed in the ED between 1 December and 31 December 2019 with the following infections were identified: acute otitis media, human and animal bites, pyelonephritis, lower urinary tract infections, cellulitis, cough, infective exacerbation of chronic obstructive pulmonary disease, pneumonia, sore throat, sinusitis, and diverticulitis. OUTCOME MEASURE: Excess antibiotic use due to either a protracted course length, or not meeting criteria for antibiotics. RESULTS: 395 patients (260 adults and 135 children) were identified. Of the 1215 days of antibiotic therapy, 198 (16%) were excess because of protracted course lengths. In terms of antibiotic defined daily doses (DDD), there were 1201.5 antibiotic DDD prescribed, of which 232 (19%) DDD were excess because of protracted course lengths. If both protracted courses and unnecessary antibiotic use were included, then 321 (27%) DDD were excess. Excess antibiotic use and total antibiotic use by infection group were: 123/546 (23%) DDD in lower respiratory tract infection, 46/59 (79%) in upper respiratory tract infection, 44/231 (19%) in upper and lower urinary tract infection, 0/113 (0%) cellulitis, 77/180 (43%) bites, and 30/40 (75%) diverticulitis. Excess antibiotic use, as a proportion of all antibiotic use in the ED, was 321/4291 (7.5%) DDD, and of whole hospital antibiotic use, the ED's excess use was 321/33 566 (0.96%). CONCLUSION: Adoption of NICE antibiotic prescribing guidelines for common infections has the potential to reduce total antibiotic use in the ED by 7.5% and contribute to the hospital-wide antibiotic stewardship programme.

Glucose-Induced ß-Cell Dysfunction In Vivo: Evidence for a Causal Role of C-jun N-terminal Kinase Pathway.

Prolonged elevation of glucose can adversely affect ß-cell function. Oxidative stress, which has been implicated in glucose-induced ß-cell dysfunction, can activate c-jun N-terminal kinase (JNK). However, whether JNK is causal in glucose-induced ß-cell dysfunction in vivo is unclear. Therefore, we aimed at investigating the causal role of JNK activation in in vivo models of glucose-induced ß-cell dysfunction. Glucose-induced ß-cell dysfunction was investigated in the presence or absence of JNK inhibition. JNK inhibition was achieved using either (i) the JNK-specific inhibitor SP600125 or (ii) JNK-1-null mice. (i) Rats or mice were infused intravenously with saline or glucose with or without SP600125. (ii) JNK-1 null mice and their littermate wild-type controls were infused intravenously with saline or glucose. Following the glucose infusion periods in rats and mice, ß-cell function was assessed in isolated islets or in vivo using hyperglycemic clamps. Forty-eight-hour hyperglycemia at ~20 mM in rats or 96-hour hyperglycemia at ~13 mM in mice impaired ß-cell function in isolated islets and in vivo. Inhibition of JNK using either SP600125 or JNK-1-null mice prevented glucose-induced ß-cell dysfunction in isolated islets and in vivo. Islets of JNK-1-null mice exposed to hyperglycemia in vivo showed an increase in Pdx-1 and insulin 2 mRNA, whereas islets of wild-type mice did not. Together, these data show that JNK pathway is involved in glucose-induced ß-cell dysfunction in vivo and is thus a potential therapeutic target for type 2 diabetes.

Electrochemical monitoring of single nanoparticle collisions at mercury-modified platinum ultramicroelectrodes.

Here, we report a potentiometric method for detecting single platinum nanoparticles (Pt NPs) by measuring a change in open-circuit potential (OCP) instead of the current during single Pt NP collisions with the mercury-modified Pt ultramicroelectrode (Hg/Pt UME). Similar to the current-time (i-t) response reported previously at Hg/Pt UMEs, the OCP-time (v-t) response consists of repeated potential transient signals that return to the background level. This is because Hg poisons the Pt NP after collision with the Hg/Pt UME due to amalgamation and results in deactivation of the redox reaction. For individual Pt NP collisions the amplitude of the OCP signal reaches a maximum and decays to the background level at a slower rate compared to the comparable i-t response. Due to this, OCP events are broader and more symmetrical in shape compared to i-t "spikes." The collision frequency of Pt NPs derived from v-t plots (0.007 to 0.020 pM(-1) s(-1)) is in good agreement with the value derived from i-t plots recorded at Hg/Pt UMEs (0.016 to 0.024 pM(-1) s(-1)) under similar conditions and was found to scale linearly with Pt NP concentration. Similar to the current response, the amplitude of the OCP response increased with the NP's size. However, unlike the change in current in a i-t response, the change in OCP in a v-t response observed during single Pt NP collisions with Hg/Pt UME is larger than the estimated change in OCP based on the theory. Therefore, the Pt NP sizes derived from the v-t response did not correlate with the TEM-derived Pt NP sizes. In spite of these results the potentiometric method has great value for electroanalysis because of its significant advantages over the amperometric method such as a simpler apparatus and higher sensitivity.