Biomarker-guided antibiotic duration for hospitalized patients with suspected sepsis: the ADAPT-sepsis randomized clinical trial

Importance: For hospitalized critically ill adults with suspected sepsis, procalcitonin (PCT) and C-reactive protein (CRP) monitoring protocols can guide the duration of antibiotic therapy, but the evidence of the effect and safety of these protocols remains uncertain. Objective: To determine whether decisions based on assessment of CRP or PCT safely results in a reduction in the duration of antibiotic therapy. Design, Setting, and Participants: A multicenter, intervention-concealed randomized clinical trial, involving 2760 adults (≥18 years), in 41 UK National Health Service (NHS) intensive care units, requiring critical care within 24 hours of initiating intravenous antibiotics for suspected sepsis and likely to continue antibiotics for at least 72 hours. Intervention: From January 1, 2018, to June 5, 2024, 918 patients were assigned to the daily PCT-guided protocol, 924 to the daily CRP-guided protocol, and 918 assigned to standard care. Main Outcomes and Measures: The primary outcomes were total duration of antibiotics (effectiveness) and all-cause mortality (safety) to 28 days. Secondary outcomes included critical care unit data and hospital stay data. Ninety-day all-cause mortality was also collected. Results: Among the randomized patients (mean age 60.2 [SD, 15.4] years; 60.3% males), there was a significant reduction in antibiotic duration from randomization to 28 days for those in the daily PCT-guided protocol compared with standard care (mean duration, 10.7 [SD, 7.6] days for standard care and 9.8 [SD, 7.2] days for PCT; mean difference, 0.88 days; 95% CI, 0.19 to 1.58, P = .01). For all-cause mortality up to 28 days, the daily PCT-guided protocol was noninferior to standard care, where the noninferiority margin was set at 5.4% (19.4% [170 of 878] of patients receiving standard care; 20.9% [184 of 879], PCT; absolute difference, 1.57; 95% CI, −2.18 to 5.32; P = .02). No difference was found in antibiotic duration for standard care vs daily CRP-guided protocol (mean duration, 10.6 [7.7] days for CRP; mean difference, 0.09; 95% CI, −0.60 to 0.79; P = .79). For all-cause mortality, the daily CRP-guided protocol was inconclusive compared with standard care (21.1% [184 of 874] for CRP; absolute difference, 1.69; 95% CI, −2.07 to 5.45; P = .03). Conclusions and Relevance: Care guided by measurement of PCT reduces antibiotic duration safely compared with standard care, but CRP does not. All-cause mortality for CRP was inconclusive. Trial Registration: isrctn.org Identifier: ISRCTN4747324

The relationship between physical activity and leg health in the broiler chicken

1. The relationship between the physical activity and leg health of broiler chickens was assessed on a semi-commercial scale. 2. Three batches of birds (2128 per batch) were raised under two lighting regimes during the photoperiod; either a step-wise change of light intensity alternating between an illuminance of 200 and 10 lx or a constant illuminance of 10 lx. The activity of focal individuals (24 per batch) was observed at 2, 4 and 6 weeks of age, and leg health assessed weekly, based on gait score, the prevalence of burns on the hock and foot pad, and angulation and rotation of the leg at the intertarsal joint. Cortical bone density and thickness and area moments of inertia of the mid-physis tibiotarsus were measured post mortem at 6 weeks of age. 3. The step-wise change in light intensity did not affect overall performance, activity or leg health. 4. An individual bird’s activity did not affect its gait score, the prevalence of hock burn or foot pad burn, cortical density or thickness or shape of the tibiotarsus. Sex of the bird was the only factor to affect significantly the area moment of inertia in the horizontal and vertical planes of the tibiotarsus, with females showing a lower moment of inertia for both. No variable had a significant effect on cortical density or thickness. Mean cortical density was low across all birds and may indicate that, when allowed to move freely as much or as little as they choose, broiler chickens do not exercise enough or do not perform the higher impact activities required to affect bone quality. 5. These findings imply that the activity of broiler chickens raised on a semi-commercial scale is unaffected by step-wise changes in light intensity and that other husbandry measures are needed to raise activity and hence improve leg health.L. Sherlock, T.G.M. Demmers, A.E. Goodship, I.D. Mccarthy and C.M. Wathe