Managing by design

This editorial written by myself and Marc Gruber of EPFL. It explores the role of design thinking in the management of large organisations, and focuses on how design principles can be applied to the design of the workplace and the nature of work itself. As Head of Service Design at the RCA, my contribution is on how to apply design thinking methods for managers and the 6 key elements described in this approach In the last decade the importance of design and the value of design thinking as a tool for innovation has been recognized by both business and government. Design has become a strategic tool for business helping to translate technological innovation into user value, connecting with consumer needs and creating compelling product and service experiences that create new business value. In this paper we consider a further application of design thinking by considering how managers can apply it to the design of the workplace experience. Many enterprises, especially those in the knowledge economy, are defined by their human resources and their capacity to attract and retain talent. In this competitive environment the design of the employee experience and the services that support them and enable them to deliver value to the clients and colleagues, is a key differentiator. Applying design thinking to the design of work itself, the systems that support it, and the physical and virtual environments in which it takes place can help business and organizational leaders to attract and retain top talent, as well as to enhance productivity and operational effectiveness. In this paper we explore the key factors and principles by which leaders and managers can apply design thinking to transform the workplace experience and we propose 6 key elements for managers to enable that transformation and enhance social capital and business and organisational performance

The validity of trans-esophageal Doppler ultrasonography as a measure of cardiac output in critically ill adults,”

Abstract Objective: To determine the validity of the esophageal Doppler monitor (EDM) and echo-esophageal Doppler (Echo-ED) in measuring cardiac output in the critically ill. Design: Systematic search of relevant international literature and data synthesis. Search strategy: Literature search (1989)(1990)(1991)(1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003

Biomarker-guided antibiotic stewardship in suspected ventilator-associated pneumonia (VAPrapid2) : a randomised controlled trial and process evaluation

Background Ventilator-associated pneumonia is the most common intensive care unit (ICU)-acquired infection, yet accurate diagnosis remains difficult, leading to overuse of antibiotics. Low concentrations of IL-1β and IL-8 in bronchoalveolar lavage fluid have been validated as effective markers for exclusion of ventilator-associated pneumonia. The VAPrapid2 trial aimed to determine whether measurement of bronchoalveolar lavage fluid IL-1β and IL-8 could effectively and safely improve antibiotic stewardship in patients with clinically suspected ventilator-associated pneumonia. Methods VAPrapid2 was a multicentre, randomised controlled trial in patients admitted to 24 ICUs from 17 National Health Service hospital trusts across England, Scotland, and Northern Ireland. Patients were screened for eligibility and included if they were 18 years or older, intubated and mechanically ventilated for at least 48 h, and had suspected ventilator-associated pneumonia. Patients were randomly assigned (1:1) to biomarker-guided recommendation on antibiotics (intervention group) or routine use of antibiotics (control group) using a web-based randomisation service hosted by Newcastle Clinical Trials Unit. Patients were randomised using randomly permuted blocks of size four and six and stratified by site, with allocation concealment. Clinicians were masked to patient assignment for an initial period until biomarker results were reported. Bronchoalveolar lavage was done in all patients, with concentrations of IL-1β and IL-8 rapidly determined in bronchoalveolar lavage fluid from patients randomised to the biomarker-based antibiotic recommendation group. If concentrations were below a previously validated cutoff, clinicians were advised that ventilator-associated pneumonia was unlikely and to consider discontinuing antibiotics. Patients in the routine use of antibiotics group received antibiotics according to usual practice at sites. Microbiology was done on bronchoalveolar lavage fluid from all patients and ventilator-associated pneumonia was confirmed by at least 104 colony forming units per mL of bronchoalveolar lavage fluid. The primary outcome was the distribution of antibiotic-free days in the 7 days following bronchoalveolar lavage. Data were analysed on an intention-to-treat basis, with an additional per-protocol analysis that excluded patients randomly assigned to the intervention group who defaulted to routine use of antibiotics because of failure to return an adequate biomarker result. An embedded process evaluation assessed factors influencing trial adoption, recruitment, and decision making. This study is registered with ISRCTN, ISRCTN65937227, and ClinicalTrials.gov, NCT01972425. Findings Between Nov 6, 2013, and Sept 13, 2016, 360 patients were screened for inclusion in the study. 146 patients were ineligible, leaving 214 who were recruited to the study. Four patients were excluded before randomisation, meaning that 210 patients were randomly assigned to biomarker-guided recommendation on antibiotics (n=104) or routine use of antibiotics (n=106). One patient in the biomarker-guided recommendation group was withdrawn by the clinical team before bronchoscopy and so was excluded from the intention-to-treat analysis. We found no significant difference in the primary outcome of the distribution of antibiotic-free days in the 7 days following bronchoalveolar lavage in the intention-to-treat analysis (p=0·58). Bronchoalveolar lavage was associated with a small and transient increase in oxygen requirements. Established prescribing practices, reluctance for bronchoalveolar lavage, and dependence on a chain of trial-related procedures emerged as factors that impaired trial processes

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Organ-specific effects of oxygen and carbogen gas inhalation on tissue longitudinal relaxation times

Molecular oxygen has been previously shown to shorten longitudinal relaxation time (T1) in the spleen and renal cortex, but not in the liver or fat. In this study, the magnitude and temporal evolution of this effect were investigated. Medical air, oxygen, and carbogen (95% oxygen/5% CO 2) were administered sequentially in 16 healthy volunteers. T 1 maps were acquired using spoiled gradient echo sequences (TR = 3.5 ms, TE = 0.9 ms, α = 2°/8°/17°) with six acquisitions on air, 12 on oxygen, 12 on carbogen, and six to 12 back on air. Mean T1 values and change in relaxation rate were compared between each phase of gas inhalation in the liver, spleen, skeletal muscle, renal cortex, and fat by one-way analysis of variance. Oxygen-induced T1-shortening occurred in the liver in fasted subjects (P <0.001) but not in non-fasted subjects (P = 0.244). T1-shortening in spleen and renal cortex (both P <0.001) were greater than previously reported. Carbogen induced conflicting responses in different organs, suggesting a complex relationship with organ vasculature. Shortening of tissue T1 by oxygen is more pronounced and more complex than previously recognized. The effect may be useful as a biomarker of arterial flow and oxygen delivery to vascular beds. © 2007 Wiley-Liss, Inc

‘In a dark place, we find ourselves’: light intensity in critical care units

Intensive care units provide specialised care for critically ill patients around the clock. However, intensive care unit patients have disrupted circadian rhythms. Furthermore, disrupted circadian rhythms are associated with worse outcome. As light is the most powerful ‘re-setter’ of circadian rhythm, we measured light intensity on intensive care unit. Light intensity was low compared to daylight during the ‘day’; frequent bright light interruptions occurred over ‘night’. These findings are predicted to disrupt circadian rhythms and impair entrainment to external time. Bright lighting during daytime and black out masks at night might help maintain biological rhythms in critically ill patients and improve clinical outcomes

Effectiveness of biomarker-based exclusion of ventilator-acquired pneumonia to reduce antibiotic use (VAPrapid-2): study protocol for a randomised controlled trial.

BACKGROUND: Ventilator-acquired pneumonia (VAP) is a common reason for antimicrobial therapy in the intensive care unit (ICU). Biomarker-based diagnostics could improve antimicrobial stewardship through rapid exclusion of VAP. Bronchoalveloar lavage (BAL) fluid biomarkers have previously been shown to allow the exclusion of VAP with high confidence. METHODS/DESIGN: This is a prospective, multi-centre, randomised, controlled trial to determine whether a rapid biomarker-based exclusion of VAP results in fewer antibiotics and improved antimicrobial management. Patients with clinically suspected VAP undergo BAL, and VAP is confirmed by growth of a potential pathogen at [≥] 10(4) colony-forming units per millilitre (CFU/ml). Patients are randomised 1:1, to either a 'biomarker-guided recommendation on antibiotics' in which BAL fluid is tested for IL-1β and IL-8 in addition to routine microbiology testing, or to 'routine use of antibiotics' in which BAL undergoes routine microbiology testing only. Clinical teams are blinded to intervention until 6 hours after randomisation, when biomarker results are reported to the clinician. The primary outcome is a change in the frequency distribution of antibiotic-free days (AFD) in the 7 days following BAL. Secondary outcome measures include antibiotic use at 14 and 28 days; ventilator-free days; 28-day mortality and ICU mortality; sequential organ failure assessment (SOFA) at days 3, 7 and 14; duration of stay in critical care and the hospital; antibiotic-associated infections; and antibiotic-resistant pathogen cultures up to hospital discharge, death or 56 days. A healthcare-resource-utilisation analysis will be calculated from the duration of critical care and hospital stay. In addition, safety data will be collected with respect to performing BAL. A sample size of 210 will be required to detect a clinically significant shift in the distribution of AFD towards more patients having fewer antibiotics and therefore more AFD. DISCUSSION: This trial will test whether a rapid biomarker-based exclusion of VAP results in rapid discontinuation of antibiotics and therefore improves antibiotic management in patients with suspected VAP. TRIAL REGISTRATION: ISRCTN65937227 . Registered on 22 August 2013. ClinicalTrials.gov, NCT01972425 . Registered on 24 October 2013

The burden of multimorbidity-associated acute hospital admissions in Malawi and Tanzania:a prospective multicentre cohort study

Background: The global burden of multimorbidity—the coexistence of two or more long-term conditions—is increasing. Limited access to primary care in sub-Saharan Africa means acute hospital admission is often the sentinel multimorbidity presentation. This prospective multicentre cohort study aimed to describe the burden, constituent diseases, and outcomes of multimorbidity among patients acutely admitted to hospital in Malawi and Tanzania. Methods: Adults (ie, those aged ≥18 years) admitted to four hospitals (two tertiary and two district hospitals) with acute medical conditions were consecutively recruited within 24 h of presentation and followed up for 90 days. We estimated the prevalence of HIV infection, diabetes, hypertension, and chronic kidney disease using commercially available point-of-care tests, and captured self-reported and clinical diagnoses (n/N [%]). Health economic data were summarised by median and IQR and modelled using generalised linear models. All-cause 90-day mortality was summarised with Kalplan–Meier plots and analysed using Cox regression models. Findings: 1407 adults (657 [46·7%] were female and 750 [53·3%] were male; mean age was 52·3 years [SD 18·4]) were recruited. We examined multimorbidity prevalence in 1007 participants admitted to three hospitals that accept admissions directly from the community. Multimorbidity was found in 473 (47·0%) of 1007 participants and 292 (29·0%) had a single long-term condition. Outcomes at 90 days were determined for 1317 (93·6%) of 1407 participants. Adjusted 90-day mortality was higher in participants with multimorbidity (335 [41·7%] of 804; hazard ratio 1·5 [95% CI 1·1–2·1]) and those with one long-term condition (80 [28·3%] of 283; 1·5 [1·0–2·1]); compared with those with no long-term conditions (31 [13·5%] of 230). Health-related quality of life was lower in participants with multimorbidity compared with those with one long-term condition (median 0·402 [IQR –0·037 to 0·644] vs 0·557 [0·140 to 0·730]; p=0·005) at baseline, and at final observation (0·858 [0·667 to 1·00] vs 1·00 [0·589 to 1·00] respectively; p=0·01). In Tanzania, medical costs incurred by patients were higher in participants with multimorbidity compared with those with one long-term condition (relative effect 5·77 [95% CI 2·99–11·15]; p&lt;0·0001). Interpretation: Multimorbidity is common in patients admitted to hospital in Malawi and Tanzania and associated with worse survival and increased cost. Multimorbidity is an urgent public health threat that requires fundamental health-care delivery reform to address population needs. Funding: National Institute for Health and Care Research and Wellcome Trust. Translations: For the Chichewa and Kiswahili translations of the abstract see Supplementary Materials section.</p

Biomarker-Guided Antibiotic Duration for Hospitalized Patients With Suspected Sepsis

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

Diagnostic accuracy of pulmonary host inflammatory mediators in the exclusion of ventilator-acquired pneumonia.

BACKGROUND: Excessive use of empirical antibiotics is common in critically ill patients. Rapid biomarker-based exclusion of infection may improve antibiotic stewardship in ventilator-acquired pneumonia (VAP). However, successful validation of the usefulness of potential markers in this setting is exceptionally rare. OBJECTIVES: We sought to validate the capacity for specific host inflammatory mediators to exclude pneumonia in patients with suspected VAP. METHODS: A prospective, multicentre, validation study of patients with suspected VAP was conducted in 12 intensive care units. VAP was confirmed following bronchoscopy by culture of a potential pathogen in bronchoalveolar lavage fluid (BALF) at >10(4) colony forming units per millilitre (cfu/mL). Interleukin-1 beta (IL-1β), IL-8, matrix metalloproteinase-8 (MMP-8), MMP-9 and human neutrophil elastase (HNE) were quantified in BALF. Diagnostic utility was determined for biomarkers individually and in combination. RESULTS: Paired BALF culture and biomarker results were available for 150 patients. 53 patients (35%) had VAP and 97 (65%) patients formed the non-VAP group. All biomarkers were significantly higher in the VAP group (p<0.001). The area under the receiver operator characteristic curve for IL-1β was 0.81; IL-8, 0.74; MMP-8, 0.76; MMP-9, 0.79 and HNE, 0.78. A combination of IL-1β and IL-8, at the optimal cut-point, excluded VAP with a sensitivity of 100%, a specificity of 44.3% and a post-test probability of 0% (95% CI 0% to 9.2%). CONCLUSIONS: Low BALF IL-1β in combination with IL-8 confidently excludes VAP and could form a rapid biomarker-based rule-out test, with the potential to improve antibiotic stewardship