Angus, Derek C.

AbstractClinical decision-making is based on knowledge, expertise, and authority, with clinicians approving almost every intervention—the starting point for delivery of “All the right care, but only the right care,” an unachieved healthcare quality improvement goal. Unaided clinicians suffer from human cognitive limitations and biases when decisions are based only on their training, expertise, and experience. Electronic health records (EHRs) could improve healthcare with robust decision-support tools that reduce unwarranted variation of clinician decisions and actions. Current EHRs, focused on results review, documentation, and accounting, are awkward, time-consuming, and contribute to clinician stress and burnout. Decision-support tools could reduce clinician burden and enable replicable clinician decisions and actions that personalize patient care. Most current clinical decision-support tools or aids lack detail and neither reduce burden nor enable replicable actions. Clinicians must provide subjective interpretation and missing logic, thus introducing personal biases and mindless, unwarranted, variation from evidence-based practice. Replicability occurs when different clinicians, with the same patient information and context, come to the same decision and action. We propose a feasible subset of therapeutic decision-support tools based on credible clinical outcome evidence: computer protocols leading to replicable clinician actions (eActions). eActions enable different clinicians to make consistent decisions and actions when faced with the same patient input data. eActions embrace good everyday decision-making informed by evidence, experience, EHR data, and individual patient status. eActions can reduce unwarranted variation, increase quality of clinical care and research, reduce EHR noise, and could enable a learning healthcare system.

Abstract Rationale Urinary TIMP-2 (tissue inhibitor of metalloproteinases-2) and IGFBP7 (insulin-like growth factor–binding protein 7) can predict acute kidney injury (AKI) in patients with sepsis. Objectives To address critical questions about whether biomarkers can inform the response to treatment and whether they might be used to guide therapy, as most sepsis patients present with AKI. Methods We measured [TIMP-2] · [IGFBP7] before and after a 6-hour resuscitation in 688 patients with septic shock enrolled in the ProCESS (Protocol-based Care for Early Septic Shock) trial. Our primary endpoint was stage 3 AKI, renal replacement therapy, or death within 7 days. Measurements and Main Results: The endpoint was reached in 113 patients (16.4%). In patients with negative [TIMP-2] · [IGFBP7] at baseline, those who became positive (>0.3 U) after resuscitation had three-times higher risk compared with those who remained negative (21.8% vs. 8.5%; P = 0.01; odds ratio [OR], 3.0; 95% confidence interval [CI], 1.31–6.87). Conversely, compared with patients with a positive biomarker at baseline that were still positive at Hour 6, risk was reduced for patients who became negative (23.8% vs. 9.8%; P = 0.01; OR, 2.15; 95% CI, 1.17–3.95). A positive [TIMP-2] · [IGFBP7] after resuscitation was associated with worse outcomes in both patients with and without AKI at that time point. The clinical response to resuscitation, as judged by the Acute Physiology and Chronic Health Evaluation II score, was weakly predictive of the endpoint (area under the curve, 0.68; 95% CI, 0.62–0.73) and improved with addition of [TIMP-2] · [IGFBP7] (0.72; 95% CI, 0.66–0.77; P = 0.03). Different resuscitation protocols did not alter biomarker trajectories, nor did they alter outcomes in biomarker-positive or biomarker-negative patients. However, biomarker trajectories were associated with outcomes. Conclusions Changes in urinary [TIMP-2] · [IGFBP7] after initial fluid resuscitation identify patients with sepsis who have differing risk for progression of AKI. Clinical trial registered with www.clinicaltrials.gov (NCT 00510835).

Abstract An estimated 14.1 million patients survive sepsis each year. Many survivors experience poor long-term outcomes, including new or worsened neuropsychological impairment; physical disability; and vulnerability to further health deterioration, including recurrent infection, cardiovascular events, and acute renal failure. However, clinical trials and guidelines have focused on shorter-term survival, so there are few data on promoting longer-term recovery. To address this unmet need, the International Sepsis Forum convened a colloquium in February 2018 titled “Understanding and Enhancing Sepsis Survivorship.” The goals were to identify gaps and limitations of current research and shorter- and longer-term priorities for understanding and enhancing sepsis survivorship. Twenty-six experts from eight countries participated. The top short-term priorities identified by nominal group technique culminating in formal voting were to better leverage existing databases for research, develop and disseminate educational resources on postsepsis morbidity, and partner with sepsis survivors to define and achieve research priorities. The top longer-term priorities were to study mechanisms of long-term morbidity through large cohort studies with deep phenotyping, build a harmonized global sepsis registry to facilitate enrollment in cohorts and trials, and complete detailed longitudinal follow-up to characterize the diversity of recovery experiences. This perspective reviews colloquium discussions, the identified priorities, and current initiatives to address them.