In 2013, New York began requiring hospitals to follow protocols for the early identification and treatment of sepsis. However, there is controversy about whether more rapid treatment of sepsis ...improves outcomes in patients.
We studied data from patients with sepsis and septic shock that were reported to the New York State Department of Health from April 1, 2014, to June 30, 2016. Patients had a sepsis protocol initiated within 6 hours after arrival in the emergency department and had all items in a 3-hour bundle of care for patients with sepsis (i.e., blood cultures, broad-spectrum antibiotic agents, and lactate measurement) completed within 12 hours. Multilevel models were used to assess the associations between the time until completion of the 3-hour bundle and risk-adjusted mortality. We also examined the times to the administration of antibiotics and to the completion of an initial bolus of intravenous fluid.
Among 49,331 patients at 149 hospitals, 40,696 (82.5%) had the 3-hour bundle completed within 3 hours. The median time to completion of the 3-hour bundle was 1.30 hours (interquartile range, 0.65 to 2.35), the median time to the administration of antibiotics was 0.95 hours (interquartile range, 0.35 to 1.95), and the median time to completion of the fluid bolus was 2.56 hours (interquartile range, 1.33 to 4.20). Among patients who had the 3-hour bundle completed within 12 hours, a longer time to the completion of the bundle was associated with higher risk-adjusted in-hospital mortality (odds ratio, 1.04 per hour; 95% confidence interval CI, 1.02 to 1.05; P<0.001), as was a longer time to the administration of antibiotics (odds ratio, 1.04 per hour; 95% CI, 1.03 to 1.06; P<0.001) but not a longer time to the completion of a bolus of intravenous fluids (odds ratio, 1.01 per hour; 95% CI, 0.99 to 1.02; P=0.21).
More rapid completion of a 3-hour bundle of sepsis care and rapid administration of antibiotics, but not rapid completion of an initial bolus of intravenous fluids, were associated with lower risk-adjusted in-hospital mortality. (Funded by the National Institutes of Health and others.).
Both quality improvement and clinical research efforts over the past few decades have focused on consensus definition of sepsis and acute respiratory distress syndrome (ARDS). Although clinical ...definitions based on readily available clinical data have advanced recognition and timely use of broad supportive treatments, they likely hinder the identification of more targeted therapies that manipulate select biological mechanisms underlying critical illness. Sepsis and ARDS are by definition heterogeneous, and patients vary in both their underlying biology and their severity of illness. We have long been able to identify subtypes of sepsis and ARDS that confer different prognoses. The key is that we are now on the verge of identifying subtypes that may confer different response to therapy. In this perspective, inspired by a 2015 American Thoracic Society International Conference Symposium entitled "Lumpers and Splitters: Phenotyping in Critical Illness," we highlight promising approaches to uncovering patient subtypes that may predict treatment responsiveness and not just differences in prognosis. We then discuss how this information can be leveraged to improve the success and translatability of clinical trials by using predictive enrichment and other design strategies. Last, we discuss the challenges and limitations to identifying biomarkers and endotypes and incorporating them into routine clinical practice.
Intensive care survivors often experience post-intensive care sequelae, which are frequently gathered together under the term "post-intensive care syndrome" (PICS). The consequences of PICS on ...quality of life, health-related costs and hospital readmissions are real public health problems. In the present Viewpoint, we summarize current knowledge and gaps in our understanding of PICS and approaches to management.
Alongside advances in understanding the pathophysiology of sepsis, there have been tremendous strides in understanding the pervasive role of the gut microbiota in systemic host resistance. In ...pre-clinical models, a diverse and balanced gut microbiota enhances host immunity to both enteric and systemic pathogens. Disturbance of this balance increases susceptibility to sepsis and sepsis-related organ dysfunction, while restoration of the gut microbiome is protective. Patients with sepsis have a profoundly distorted composition of the intestinal microbiota, but the impact and therapeutic potential of the microbiome is not well-established in human sepsis. Modulation of the microbiota consists of either resupplying the pool of beneficial microbes by administration of probiotics, improving the intestinal microenvironment to enhance the growth of beneficial species by dietary interventions and prebiotics, or by totally recolonizing the gut with a fecal microbiota transplantation (FMT). We propose that there are three potential opportunities to utilize these treatment modalities over the course of sepsis: to decrease sepsis incidence, to improve sepsis outcome, and to decrease late mortality after sepsis. Exploring these three avenues will provide insight into how disturbances of the microbiota can predispose to, or even perpetuate the dysregulated immune response associated with this syndrome, which in turn could be associated with improved sepsis management.
Hospitalizations for severe sepsis are common, and a growing number of patients survive to hospital discharge. Nonetheless, little is known about survivors' post-discharge healthcare use.
To measure ...inpatient healthcare use of severe sepsis survivors compared with patients' own presepsis resource use and the resource use of survivors of otherwise similar nonsepsis hospitalizations.
This is an observational cohort study of survivors of severe sepsis and nonsepsis hospitalizations identified from participants in the Health and Retirement Study with linked Medicare claims, 1998-2005. We matched severe sepsis and nonsepsis hospitalizations by demographics, comorbidity burden, premorbid disability, hospitalization length, and intensive care use.
Using Medicare claims, we measured patients' use of inpatient facilities (hospitals, long-term acute care hospitals, and skilled nursing facilities) in the 2 years surrounding hospitalization. Severe sepsis survivors spent more days (median, 16 interquartile range, 3-45 vs. 7 0-29; P < 0.001) and a higher proportion of days alive (median, 9.6% interquartile range, 1.4-33.8% vs. 1.9% 0.0-7.9%; P < 0.001) admitted to facilities in the year after hospitalization, compared with the year prior. The increase in facility-days was similar for nonsepsis hospitalizations. However, the severe sepsis cohort experienced greater post-discharge mortality (44.2% 95% confidence interval, 41.3-47.2% vs. 31.4% 95% confidence interval, 28.6-34.2% at 1 year), a steeper decline in days spent at home (difference-in-differences, -38.6 d 95% confidence interval, -50.9 to 26.3; P < 0.001), and a greater increase in the proportion of days alive spent in a facility (difference-in-differences, 5.4% 95% confidence interval, 2.8-8.1%; P < 0.001).
Healthcare use is markedly elevated after severe sepsis, and post-discharge management may be an opportunity to reduce resource use.
In 2015, all 193 member countries of the United Nations adopted the 2030 Agenda for Sustainable Development. It includes 17 Sustainable Development Goals (SDGs). Building on the principle of “leaving ...no one behind,” it emphasizes a holistic approach to achieving sustainable development 1. The 2020 environmental, social and governance (ESG) scoring and reporting document from the Organization for Economic Co-operation and Development (OECD) notes that sustainability investing has grown, primarily due to the number of funds and investors that have added ESG approaches to their overall agenda. Corporations, central banks and the public sector are placing a new emphasis on a greener environment and low-carbon economy 2. The 2020s was to be a decade of action but progress has been slow, stalled or reversed in meeting the 17 SDG targets 3. OECD’s quantitative analysis provides an indication of the progress made and challenges still ahead with regard to sustainable development. The wide variety of metrics, methodologies, and approaches indicate a high number of disparate outcomes that are open to interpretation 4.
This Special Issue on “Business Models and Sustainable Development Goals (SDG)” presents five research studies that examine transformative business models designed to support the United Nations SDG ...Agenda for 2030. The studies examine SDGs from the firm to national levels. Every organization has a business model that defines how the organization is designed to function. It is the engine that powers an organization, defining the value proposition of the venture, how it balances resources with the ecosystem where it operates, and how it generates cash flow and creates value. Changes to an organization’s business model are recognized as a fundamental approach to implementing innovations for sustainability. The capability to transform or transition to new business models is an important source of competitive advantage, providing leverage to improve the performance of an organization. A sustainable business model includes pro-active management, monetary and non-monetary value for a broad range of stakeholders, and takes a long-term perspective. A sustainable business model is where change, success, and hope for our planet’s future rests.
Cancer and its treatment are known to be important risk factors for sepsis, contributing to an estimated 12% of U.S. sepsis admissions in the 1990s. However, cancer treatment has evolved markedly ...over the past 2 decades. We sought to examine how cancer-related sepsis differs from non-cancer-related sepsis.
Observational cohort.
National Readmissions Database (2013-2014), containing all-payer claims for 49% of U.S.
A total of 1,104,363 sepsis hospitalizations.
We identified sepsis hospitalizations in the U.S. National Readmissions Database using explicit codes for severe sepsis, septic shock, or Dombrovskiy criteria (concomitant codes for infection and organ dysfunction). We classified hospitalizations as cancer-related versus non-cancer-related sepsis based on the presence of secondary diagnosis codes for malignancy. We compared characteristics (site of infection and organ dysfunction) and outcomes (in-hospital mortality and 30-d readmissions) of cancer-related versus non-cancer-related sepsis hospitalizations. We also completed subgroup analyses by age, cancer types, and specific cancer diagnoses.
There were 27,481,517 hospitalizations in National Readmissions Database 2013-2014, of which 1,104,363 (4.0%) were for sepsis and 4,150,998 (15.1%) were cancer related. In-hospital mortality in cancer-related sepsis was 27.9% versus 19.5% in non-cancer-related sepsis. The median count of organ dysfunctions was indistinguishable, but the rate of specific organ dysfunctions differed by small amounts (e.g., hematologic dysfunction 20.1% in cancer-related sepsis vs 16.6% in non-cancer-related sepsis; p < 0.001). Cancer-related sepsis was associated with an adjusted absolute increase in in-hospital mortality ranging from 2.2% to 15.2% compared with non-cancer-related sepsis. The mortality difference was greatest in younger adults and waned with age. Patients (23.2%) discharged from cancer-related sepsis were rehospitalized within 30 days, compared with 20.1% in non-cancer-related sepsis (p < 0.001).
In this cohort of over 1 million U.S. sepsis hospitalizations, more than one in five were cancer related. The difference in mortality varies substantially across age spectrum and is greatest in younger adults. Readmissions were more common after cancer-related sepsis.
In observational studies of the general population, higher body mass index (BMI) has been associated with increased incidence of and mortality from bloodstream infection (BSI) and sepsis. On the ...other hand, higher BMI has been observed to be apparently protective among patients with infection and sepsis. We aimed to evaluate the causal association of BMI with risk of and mortality from BSI.
We used a population-based cohort in Norway followed from 1995 to 2017 (the Trøndelag Health Study HUNT), and carried out linear and nonlinear Mendelian randomization analyses. Among 55,908 participants, the mean age at enrollment was 48.3 years, 26,324 (47.1%) were men, and mean BMI was 26.3 kg/m2. During a median 21 years of follow-up, 2,547 (4.6%) participants experienced a BSI, and 451 (0.8%) died from BSI. Compared with a genetically predicted BMI of 25 kg/m2, a genetically predicted BMI of 30 kg/m2 was associated with a hazard ratio for BSI incidence of 1.78 (95% CI: 1.40 to 2.27; p < 0.001) and for BSI mortality of 2.56 (95% CI: 1.31 to 4.99; p = 0.006) in the general population, and a hazard ratio for BSI mortality of 2.34 (95% CI: 1.11 to 4.94; p = 0.025) in an inverse-probability-weighted analysis of patients with BSI. Limitations of this study include a risk of pleiotropic effects that may affect causal inference, and that only participants of European ancestry were considered.
Supportive of a causal relationship, genetically predicted BMI was positively associated with BSI incidence and mortality in this cohort. Our findings contradict the "obesity paradox," where previous traditional epidemiological studies have found increased BMI to be apparently protective in terms of mortality for patients with BSI or sepsis.
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