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Background: Primary care is a critical partner for antimicrobial stewardship efforts given its high human antibiotic usage. Peer comparison audit and feedback (A&F) is often used to reduce inappropriate antibiotic prescribing. The design and implementation of A&F may impact its effectiveness. There are no best practice guidelines for peer comparison A&F in antibiotic prescribing in primary care., Objective: To develop best practice guidelines for peer comparison A&F for antibiotic prescribing in primary care in high income countries by leveraging international expertise via the Joint Programming Initiative on Antimicrobial Resistance-Primary Care Antibiotic Audit and Feedback Network., Methods: We used a modified Delphi process to achieve convergence of expert opinions on best practice statements for peer comparison A&F based on existing evidence and theory. Three rounds were performed, each with online surveys and virtual meetings to enable discussion and rating of each best practice statement. A five-point Likert scale was used to rate consensus with a median threshold score of 4 to indicate a consensus statement., Results: The final set of guidelines include 13 best practice statements in four categories: general considerations (n = 3), selecting feedback recipients (n = 1), data and indicator selection (n = 4), and feedback delivery (n = 5)., Conclusion: We report an expert-derived best practice recommendations for designing and evaluating peer comparison A&F for antibiotic prescribing in primary care. These 13 statements can be used by A&F designers to optimize the impact of their quality improvement interventions, and improve antibiotic prescribing in primary care., (© 2023. Crown.)

Background: Audit and feedback aims to improve patient care by comparing healthcare performance against explicit standards. It is used to monitor and improve patient care, including through National Clinical Audit (NCA) programmes in the UK. Variability in effectiveness of audit and feedback is attributed to intervention design; separate randomised trials to address multiple questions about how to optimise effectiveness would be inefficient. We evaluated different feedback modifications to identify leading candidates for further "real-world" evaluation., Methods: Using an online fractional factorial screening experiment, we randomised recipients of feedback from five UK NCAs to different combinations of six feedback modifications applied within an audit report excerpt: use effective comparators, provide multimodal feedback, recommend specific actions, provide optional detail, incorporate the patient voice, and minimise cognitive load. Outcomes, assessed immediately after exposure to the online modifications, included intention to enact audit standards (primary outcome, ranked on a scale of -3 to +3, tailored to the NCA), comprehension, user experience, and engagement., Results: We randomised 1241 participants (clinicians, managers, and audit staff) between April and October 2019. Inappropriate repeated participant completion occurred; we conservatively excluded participant entries during the relevant period, leaving a primary analysis population of 638 (51.4%) participants. None of the six feedback modifications had an independent effect on intention across the five NCAs. We observed both synergistic and antagonistic effects across outcomes when modifications were combined; the specific NCA and whether recipients had a clinical role had dominant influences on outcome, and there was an antagonistic interaction between multimodal feedback and optional detail. Among clinical participants, predicted intention ranged from 1.22 (95% confidence interval 0.72, 1.72) for the least effective combination in which multimodal feedback, optional detail, and reduced cognitive load were applied within the audit report, up to 2.40 (95% CI 1.88, 2.93) for the most effective combination including multimodal feedback, specific actions, patient voice, and reduced cognitive load., Conclusion: Potentially important synergistic and antagonistic effects were identified across combinations of feedback modifications, audit programmes, and recipients, suggesting that feedback designers must explicitly consider how different features of feedback may interact to achieve (or undermine) the desired effects., Trial Registration: International Standard Randomised Controlled Trial Number: ISRCTN41584028., (© 2022. The Author(s).)

Background: Glucagon serves as an important regulatory hormone for regulating blood glucose concentration with tight feedback control exerted by insulin and glucose. There are critical gaps in our understanding of glucagon kinetics, pancreatic α cell function and intra-islet feedback network that are disrupted in type 1 diabetes. This is important for translational research applications of evolving dual-hormone (insulin + glucagon) closed-loop artificial pancreas algorithms and their usage in type 1 diabetes. Thus, it is important to accurately measure glucagon kinetics in vivo and to develop robust models of glucose-insulin-glucagon interplay that could inform next generation of artificial pancreas algorithms., Methods: Here, we describe the administration of novel 13 C 15 N heavy isotope-containing glucagon tracers-FF glucagon [(Phe 6 13 C 9 , 15 N; Phe 22 13 C 9 , 15 N)] and FFLA glucagon [(Phe 6 13 C 9 , 15 N; Phe 22 13 C 9 , 15 N; Leu 14 13 C 6 , 15 N; Ala 19 13 C 3 )] followed by anti-glucagon antibody-based enrichment and LC-MS/MS based-targeted assays using high-resolution mass spectrometry to determine levels of infused glucagon in plasma samples. The optimized assay results were applied for measurement of glucagon turnover in subjects with and without type 1 diabetes infused with isotopically labeled glucagon tracers., Results: The limit of quantitation was found to be 1.56 pg/ml using stable isotope-labeled glucagon as an internal standard. Intra and inter-assay variability was < 6% and < 16%, respectively, for FF glucagon while it was < 5% and < 23%, respectively, for FFLA glucagon. Further, we carried out a novel isotope dilution technique using glucagon tracers for studying glucagon kinetics in type 1 diabetes., Conclusions: The methods described in this study for simultaneous detection and quantitation of glucagon tracers have clinical utility for investigating glucagon kinetics in vivo in humans., (© 2022. The Author(s).)

Background: Forty per cent of critically ill patients are affected by intensive care unit-acquired weakness (ICU-AW), to which skeletal muscle wasting makes a substantial contribution. This can impair outcomes in hospital, and can cause long-term physical disability after hospital discharge. No effective mitigating strategies have yet been identified. Application of a repetitive vascular occlusion stimulus (RVOS) a limb pressure cuff inducing brief repeated cycles of ischaemia and reperfusion, can limit disuse muscle atrophy in both healthy controls and bed-bound patients recovering from knee surgery. We wish to determine whether RVOS might be effective in mitigating against muscle wasting in the ICU. Given that RVOS can also improve vascular function in healthy controls, we also wish to assess such effects in the critically ill. We here describe a pilot study to assess whether RVOS application is safe, tolerable, feasible and acceptable for ICU patients., Methods: This is a randomised interventional feasibility trial. Thirty-two ventilated adult ICU patients with multiorgan failure will be recruited within 48 h of admission and randomised to either the intervention arm or the control arm. Intervention participants will receive RVOS twice daily (except only once on day 1) for up to 10 days or until ICU discharge. Serious adverse events and tolerability (pain score) will be recorded; feasibility of trial procedures will be assessed against pre-specified criteria and acceptability by semi-structured interview. Together with vascular function, muscle mass and quality will be assessed using ultrasound and measures of physical function at baseline, on days 6 and 11 of study enrolment, and at ICU and hospital discharge. Blood and urine biomarkers of muscle metabolism, vascular function, inflammation and DNA damage/repair mechanism will also be analysed. The Health questionnaire will be completed 3 months after hospital discharge., Discussion: If this study demonstrates feasibility, the derived data will be used to inform the design (and sample size) of an appropriately-powered prospective trial to clarify whether RVOS can help preserve muscle mass/improve vascular function in critically ill patients., Trial Registration: ISRCTN Registry, ISRCTN44340629. Registered on 26 October 2017.

Background: Post-operative pulmonary complications (POPC) are common, predictable and associated with increased morbidity and mortality, independent of pre-operative risk. Interventions to reduce the incidence of POPC have been studied individually, but the use of a care bundle has not been widely investigated. The purpose of our work was to use Delphi consensus methodology and an independently chosen expert panel to formulate a care bundle for patients identified as being at high of POPC, as preparation towards an evaluation of its effectiveness at reducing POPC., Methods: We performed a survey of members of the ESICM POIC section to inform a Delphi consensus and to share their opinions on a care bundle to reduce POPC, the POPC-CB. We formed a team of 36 experts to participate in and complete an email-based Delphi consensus over three rounds, leading to the formulation of the POPC-CB., Results: The survey had 362 respondents and informed the design of the Delphi consensus. The Delphi consensus resulted in a proposed POPC-CB that incorporates components before surgery-supervised exercise programmes and inspiratory muscle training, during surgery, low tidal volume ventilation with individualised PEEP (positive end-expiratory pressure), use of routine monitoring to avoid hyperoxia and efforts made to limit neuromuscular blockade, and post-operatively, deep breathing exercises and elevation of the head of the bed., Conclusion: A care bundle has been suggested for evaluation in surgical patients at high risk of POPC. Evaluation of feasibility of both implementation and effectiveness is now indicated., Competing Interests: Not applicable.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: Footwear interventions are often prescribed to assist with the management of lower limb pain, injury and disease. Commercially available shoe insoles and orthoses are increasingly incorporating novel design features to alleviate foot and lower limb symptoms, but this may be at a cost to optimal functional performance. This study compared the immediate effects of wearing glycerine-filled insoles, contoured prefabricated orthoses, and flat insoles, on balance and gait measures., Methods: Thirty healthy adults (17 men, 13 women; mean [SD] age: 24.3 [2.5] years) performed tests of single-leg standing with eyes open (Kistler force platform), star excursion balance test, and level-ground walking (GAITRite® walkway system), under three randomised conditions: wearing glycerine-filled insoles, prefabricated orthoses, and flat (control) insoles, within their own footwear. Centre of pressure movement (anterior-posterior and mediolateral range and standard deviation, total path velocity), star excursion balance test reach distance, and temporospatial gait variables were collected. Perceived comfort of the inserts was scored immediately after use on a 100 mm visual analogue rating scale. After trialling all inserts each participant ranked their level of comfort from least to most., Results: Centre of pressure measures, star excursion balance test reach distance, or temporospatial gait variables did not differ between the three inserts (all P values >0.088). Significant between-condition differences were reported for comfort ranking (P = 0.031), but not rating scores (P = 0.638). Weak to moderate negative correlations (r values ranged between -0.368 and -0.406) were observed between visual analogue scale comfort rating for the flat insoles and prefabricated orthoses, star excursion balance test and gait measures., Conclusions: Single-leg standing balance, star excursion balance test performance, and level-ground walking patterns in asymptomatic adults do not appear to differ when wearing glycerine-filled insoles, contoured prefabricated orthoses, or flat insoles. Perceived comfort may be related to the biomechanical or clinical effectiveness of novel footwear interventions, and requires further investigation. Importantly, these findings are specific to a healthy population and further research is needed to determine the long-term effects of glycerine-filled insoles in patients with known balance impairments.