Muscle size, strength, and physical function in response to augmented calorie delivery: A TARGET sub-study.

Purpose Augmented calories may attenuate muscle loss experienced in critical illness. This exploratory sub-study assessed the effect of augmented calorie delivery on muscle mass, strength, and function. Materials and methods Patients in The Augmented versus Routine approach to Giving Energy Trial (TARGET) randomised to 1.5 kcal/ml or 1.0 kcal/ml enteral formulae at a single-centre were included. Ultrasound-derived muscle layer thickness (MLT) at quadriceps, forearm and mid-upper arm, and handgrip strength, were measured weekly from baseline to hospital discharge, and 3- and 6-months. Physical function was assessed at 3- and 6-months using the 'get up and go' and 6-min walk tests. Data are mean ± SD. Results Eighty patients were recruited (1.5 kcal: n = 38, 58 ± 14y, 60%M, APACHE II 20 ± 7; 1.0 kcal: n = 42, 54 ± 18y, 66%M, APACHE II 22 ± 10). The 1.5 kcal/ml group received more calories with no difference in quadriceps MLT at any timepoint including ICU discharge (primary outcome) (2.90 ± 1.27 vs 2.39 ± 1.06 cm; P = 0.141). Relationships were similar for all MLT measures, handgrip strength, and 6-min walk test. Patients in the 1.5 kcal/ml group had improved 'get up and go' test at 3-months (6.66 ± 1.33 vs. 9.11 ± 2.94 s; P = 0.014). Conclusion Augmented calorie delivery may not attenuate muscle loss or recovery of strength or function 6-months post-ICU, but this requires exploration in a larger trial.Lee-anne S. Chapple, Matthew J. Summers, Luke M.Weinel, Kylie Lange, Woo Han Yang, Adam M. Deane, Marianne J. Chapman, The TARGET Investigators for the Australia and New Zealand Intensive Care Society Clinical Trials Grou

Impact of itch on quality of life in people with primary biliary cholangitis: A plain language summary

What is this summary about? This is a summary of an article about people with primary biliary cholangitis (PBC) who also suffer from itch. PBC is a disease that affects the liver; itching is common in PBC and can dramatically reduce a person's quality of life. People in a study called TARGET-PBC filled in surveys about their PBC symptoms, including itching, and the effects the symptoms had on their lives. Information was also collected on the medications people were taking for their PBC and itch. What were the results? Out of 211 people with PBC who filled in the surveys, 170 (81%) had itching. More than one-third of them (37%) had itch that was clinically significant. Clinically significant itch has been defined as an itch that sometimes affects a person's sleep, makes them scratch until their skin is raw, or causes embarrassment. These people would benefit from a discussion about treatment options. Clinically significant itch was linked with worse scores on the surveys, meaning poorer quality of life. This link was true for all areas looked at, but particularly for social aspects and cognition, such as memory and concentration. Sleep was affected in most people with clinically significant itch and there were high levels of fatigue. People with clinically significant itch were more likely to be taking anti-itch medication compared with those with mild itch, but onethird of them still had not received any treatment for itch. When itch medication was used, the stepwise guidelines suggested by specialty professional societies was not usually followed. What do the results mean? Itching is problematic for the people in this study. Those with clinically significant itch have a worse quality of life compared with those with mild itch and this affects all areas of their life measured. The study also shows that people do not always receive medication for their itch, and that treatment guidelines are not always followed

Effect of therapeutic drug monitoring-based dose optimization of piperacillin/tazobactam on sepsis-related organ dysfunction in patients with sepsis: a randomized controlled trial (vol 48, pg 311, 2022)

PURPOSE: Insufficient antimicrobial exposure is associated with worse outcomes in sepsis. We evaluated whether therapeutic drug monitoring (TDM)-guided antibiotic therapy improves outcomes. METHODS: Randomized, multicenter, controlled trial from January 2017 to December 2019. Adult patients (n = 254) with sepsis or septic shock were randomly assigned 1:1 to receive continuous infusion of piperacillin/tazobactam with dosing guided by daily TDM of piperacillin or continuous infusion with a fixed dose (13.5 g/24 h if eGFR ≥ 20 mL/min). Target plasma concentration was four times the minimal inhibitory concentration (range ± 20%) of the underlying pathogen, respectively, of Pseudomonas aeruginosa in empiric situation. Primary outcome was the mean of daily total Sequential Organ Failure Assessment (SOFA) score up to day 10. RESULTS: Among 249 evaluable patients (66.3 ± 13.7 years; female, 30.9%), there was no significant difference in mean SOFA score between patients with TDM (7.9 points; 95% CI 7.1–8.7) and without TDM (8.2 points; 95% CI 7.5–9.0) (p = 0.39). Patients with TDM-guided therapy showed a lower 28-day mortality (21.6% vs. 25.8%, RR 0.8, 95% CI 0.5–1.3, p = 0.44) and a higher rate of clinical (OR 1.9; 95% CI 0.5–6.2, p = 0.30) and microbiological cure (OR 2.4; 95% CI 0.7–7.4, p = 0.12), but these differences did not reach statistical significance. Attainment of target concentration was more common in patients with TDM (37.3% vs. 14.6%, OR 4.5, CI 95%, 2.9–6.9, p < 0.001). CONCLUSION: TDM-guided therapy showed no beneficial effect in patients with sepsis and continuous infusion of piperacillin/tazobactam with regard to the mean SOFA score. Larger studies with strategies to ensure optimization of antimicrobial exposure are needed to definitively answer the question. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00134-021-06609-6