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Suggested Publications
3rd International Consensus Definitions for Sepsis and Septic Shock
This week, we suggest the reading of the 3rd International consensus definitions for sepsis and septic shock, recently published on JAMA. SUMMARY: Sepsis, a syndrome of physiologic, pathologic, and biochemical abnormalities induced by infection, is a major public health concern. Although the true incidence is unknown, sepsis is a leading cause of mortality and critical illness worldwide. Furthermore, patients who survive sepsis, often, have long-term physical, psychological, and cognitive disabilities.A 1991 consensus conference developed initial definitions of sepsis, septic shock, and organ dysfunction, which have remained largely unchanged for more than 2 decades. Recognizing the need to re-examine the current definitions, the European Society of Intensive Care Medicine and the Society of Critical Care Medicine convened a task force of 19 specialists in January 2014. A systematic literature review and Delphi consensus methods were also used for the definition and clinical criteria describing septic shock.Sepsis is a syndrome encompassing a still-uncertain pathobiology; it is life-threatening organ dysfunction caused by a dysregulated host response to infection, amplified by endogenous factors. No gold standard diagnostic test exists. Many existing terms are used interchangeably, whereas others are redundant or overly narrow. The current use of 2 or more Systemic Inflammatory Response Syndrome (SIRS) criteria to identify sepsis was unanimously considered by the task force to be unhelpful. Severity of organ dysfunction has been assessed with various scoring systems, that quantify abnormalities according to clinical findings, laboratory data, or therapeutic interventions. The predominant score in current use is the Sequential Organ Failure Assessment (SOFA): a higher SOFA score is associated with an increased probability of mortality. Patients with a SOFA score of 2 or more had an overall mortality risk of approximately 10% in a general hospital population with presumed infection. Depending on a patient’s baseline level of risk, a SOFA score of 2 or greater identified a 2- to 25-fold increased risk of dying compared with patients with a SOFA score less than 2.Septic shock is defined as a subset of sepsis in which underlying circulatory and cellular metabolism abnormalities are profound enough to substantially increase mortality. Clinical criteria for septic shock were developed with hypotension and hyperlactatemia because the combination encompasses both cellular dysfunction and cardiovascular compromise and is associated with a significantly higher risk-adjusted mortality.The authors highlighted that the task force focused on adult patients, recognizing the need to develop similar updated definitions for pediatric populations.The task force has generated new definitions that incorporate an up-to-date understanding of sepsis biology, including organ dysfunction. However, the lack of a criterion standard, precludes unambiguous validation and instead requires approximate estimations of performance across a variety of validity domains.The authors concluded that these updated definitions and clinical criteria should clarify long used descriptors and facilitate earlier recognition and more timely management of patients with sepsis or at risk of developing it. AUTHORS: Mervyn Singer, MD, FRCP; Clifford S. Deutschman, MD, MS; Christopher Warren Seymour, MD, MSc; Manu Shankar-Hari, MSc, MD, FFICM;Djillali Annane, MD, PhD; Michael Bauer, MD; Rinaldo Bellomo, MD; Gordon R. Bernard, MD; Jean-Daniel Chiche, MD, PhD; Craig M. Coopersmith, MD; Richard S. Hotchkiss, MD; Mitchell M. Levy, MD; John C. Marshall, MD; Greg S. Martin, MD, MSc; Steven M. Opal, MD; Gordon D. Rubenfeld, MD, MS; Tom van der Poll, MD, PhD; Jean-Louis Vincent, MD, PhD; Derek C. Angus, MD, MPH. To go to the full article, click here.
Cumulative vaccine and non–vaccine targeted infections
This week WAidid suggests an article just published on the Journal of the American Medical Association and titled "Association Between Estimated Cumulative Vaccine Antigen Exposure Through the First 23 Months of Life and Non–Vaccine Targeted Infections From 24 Through 47 Months of Age". SUMMARY: In the past 3 decades, the routine childhood immunization schedule in the first 2 years of life expanded from 3 vaccines against 7 diseases to 10 vaccines against 14 diseases. Some parents believe this increase in vaccine exposure is harmful to children, with specific concerns that early childhood immunization “overloads” the immune system and increases the risk for future infection. Based in part on this concern, an estimated 10% to 15% of parents are choosing delayed or alternative immunization schedules for their children.To date, the association between multiple vaccine antigen exposure and non–vaccine-targeted infections has not been tested in a US population with the current recommended immunization schedule. In addition, a 2013 Institute of Medicine committee examined existing evidence on the safety of the current schedule and concluded that additional observational safety studies were warranted. The committee specifically recommended examining the complete early childhood schedule (ages 0 through 23 months), as it relates to future adverse outcomes.The authors reported the data of the matched case-control study, in which they examined estimated cumulative vaccine antigen exposure through the first 23 months of life in children with non–vaccine-targeted infections from ages 24 through 47 months, compared with children without such infections, enrolled in 6 integrated health care organizations, that are part of the Vaccine Safety Datalink (VSD). Children, born between January 1, 2003, and September 31, 2013, continuously enrolled in the health plan from age 6 weeks through 23 months, were identified.From ages 24 through 47 months, potential non–vaccine targeted infections were identified in VSD data sets.For cases and matched controls, vaccine antigen exposure was estimated from birth through age 23 months. Antigen exposure was measured as the number of immunogenic proteins and polysaccharides in each vaccine.During the study observation period, 5 new vaccines were added to the recommended schedule, and children could have been exposed to between 193 and 435 total cumulative antigens.After exclusions, the study cohort comprised 495193 children. At the end, 193 confirmed cases with non-vaccine-targeted infections and 751 matched controls were identified.The mean estimated cumulative antigen exposure was 254.6 (53.6), and the mean estimated maximum single-day antigen exposure was 102.4 (20.4).From ages 24 through 47 months, there were 47061 events for potential non–vaccine-targeted infections. Of these diagnoses, a stratified, random sample of 385 underwent medical record review, and 193 (50.1%) were confirmed with medical record review, divided in upper respiratory infections (58.0%), lower respiratory infections (21.8%), gastrointestinal infections (9.3%), and other bacterial and viral infections (10.9%).Most cases were treated in the ED, as compared with the 44% that were admitted to the hospital. The mean estimated cumulative antigen exposure and maximum single-day antigen exposure for the cases were 240.6 (48.3) and 101.0 (18.4), respectively.The mean estimated cumulative antigen exposure and maximum single-day antigen exposure for the controls were 242.9 (51.1) and 100.5 (18.9), respectively. Between-group differences for estimated cumulative antigen exposure and maximum single day antigen exposure were −2.3 (P = 0.55) and 0.5 (P = 0.72), respectively.The authors reported that in the comparison between children with non–vaccine targeted infections from 24 through 47months, and children without infections, there was no significant difference in estimated vaccine antigen exposure in any of the primary or secondary analyses.The potential nonspecific effects of vaccination have been extensively studied. Several potential biological mechanisms for nonspecific vaccine effects have been proposed, but none have been established.The authors concluded, although they highlighted themselves some limitations (health care–seeking bias, diagnostic bias, overestimated rate of illness among the under-vaccinated), that there was no significant difference in estimated cumulative vaccine antigen exposure through the first 23 months of life among children from 24 through 47 months of age with ED and inpatient visits for infectious diseases not targeted by vaccines, compared with children without such visits. AUTHORS: Glanz JM, Newcomer SR, Daley MF, DeStefano F, Groom HC, Jackson ML, Lewin BJ, McCarthy NL, McClure DL, Narwaney KJ, Nordin JD, Zerbo O. Click here to go to the article.
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